Patent Publication Number: US-2018050082-A1

Title: Serpins for the treatment of neuroinflammatory diseases

Description:
CROSS REFERENCE TO RELATED APPLICATIONS 
     This application claims the benefit of U.S. Provisional Application No. 62/131,073, filed on Mar. 10, 2015, incorporated herein by reference in its entirety. 
    
    
     SEQUENCE LISTING 
     The instant application contains a Sequence Listing which has been filed electronically in ASCII format and is hereby incorporated by reference in its entirety. Said ASCII copy, created on Mar. 3, 2016, is named ANV002W_SL.txt and is 161,319 bytes in size. 
     FIELD OF THE INVENTION 
     The present invention relates to the use of serpins, including alpha-1 antitrypsin (A1AT or AAT), its derivatives and analogs thereof, in the prevention or treatment of neuroinflammatory diseases. In particular embodiments, the invention relates to the combination of A1AT and another anti-inflammatory therapeutic compound. The present invention further relates to methods of administering said A1AT combination. 
     BACKGROUND OF THE INVENTION 
     Alpha-1 antitrypsin (A1AT) is a member of the serpin superfamily of protease inhibitors. Normally found in serum, A1AT inhibits a wide variety of proteases and has been shown to protect tissues from the enzymes secreted by activated immune cells. Alpha-1 antitrypsin (AAT) inhibits IL-8 production as well as IL-8 binding to its receptors. A1AT also inactivates elastase to decrease extracellular matrix degradation of the blood-brain barrier. A1AT inhibits macrophage production of pro-inflammatory cytokines that are upregulated in neuromyelitis optica (NMO), a neurodegenerative disease. A1AT induces Treg cells, tolerogenic dendritic cells, and anti-inflammatory cytokines. Circulating levels of A1AT vary with a normal reference range in the blood of 1.5-3.5 g/L in humans. Since it is a negative feedback molecule that downregulates immune system activity, it is used as a marker of inflammation. 
     Serpins inactivate enzymes such as neutrophil elastase by covalently binding to the protease in a manner that inhibits enzyme activity. During infection or acute phase response, degranulation rates of immune cells increase markedly, thus high levels of serpins are required for enzyme neutralization and to limit damage to tissue. In circumstances where there are insufficient serpin concentrations in the tissue, fibrosis or scaring of the tissue can arise. 
     Several genetic mutations have been identified in humans that correspond to the incorrect folding of the beta sheets and alpha helices of A1AT and render the protein non-functional. This can cause A1AT deficiency and results in hepatic cirrhosis and fibrosis throughout the body. 
     Blood-derived A1AT has been used clinically to rescue patients deficient in A1AT. It has also been used recently to neutralize the effects of neutrophil elastase in patients with emphysema and chronic obstructive pulmonary disease. 
     Work by Subramanian et al. has demonstrated that sustained expression of human A1AT in a transgenic C57BL/6 mouse background were resistant to MOG-35-55 peptide-induced experimental autoimmune encephalomyelitis. Furthermore, hA1AT expression was also characteristic of elevated CD4+FoxP3+T reg  cell counts and diminished pro-inflammatory cytokine expression IL17, IL1b and IL6 and reduced CCR6 chemokine levels. ( Metab. Brain Dis.  26(2):107-13 (2011), incorporated by reference herein in its entirety.) 
     NMO is a rare disorder that resembles multiple sclerosis in several ways but requires a different treatment regimen for disease maintenance. Symptoms of NMO include loss of vision and spinal cord function. Optical neuritis may manifest in patients as visual impairment with decreased visual acuity. Spinal cord demyelination may manifest in patients as muscle weakness, reduced sensory proprioception or loss of bladder and bowel control. During severe flares, patients may experience acute paraparesis or quadriparesis. 
     Recently, neutrophil elastase involvement, driven by granulocte-mediated inflammation, has been demonstrated in a mouse model of NMO. (See  Mult. Scler.  18:398-408 (2012), incorporated by reference herein in its entirety.) At least two different causes are known for NMO including the presence of autoantibodies against aquaporin 4 and aberrant astrocyte activity. An increasing body of evidence also supports the contribution of Th17 cells and a role of granulocytic release at the site of inflammation. 
     Diagnosis of NMO is currently accepted as requiring two absolute criteria plus at least two supportive criteria. The absolute criteria are optic neuritis and acute myelitis whilst the supportive criteria are brain MRI not consistent with multiple sclerosis at disease onset, spinal cord MRI with contiguous T2-weighted signal abnormality extending over three or more vertebral segments and NMO-IgG seropositivity against aquaporin 4 antigen. 
     Multiple sclerosis (MS) is a heterogeneous condition consisting of recurrent and simultaneous inflammatory lesions of the spinal cord and brain causing demyelination of nerves in the central nervous system. Symptoms range widely and may be physical (motor function loss, sensory function loss, or pain) or psychological (mood alteration, depression). Several forms of MS exist including remitting and progressive forms. Specifically, forms include relapse-remitting, secondary progressive, primary progressive and progressive relapsing. 
     Diagnosis of MS is typically based on presenting symptoms with the most common diagnostic tools being neuroimaging, analysis of cerebrospinal fluid (CSF) and evoked potentials. In neuroimaging of patients suspected of having MS, MRI may be used to identify demyelinated areas of the brain and spinal cord. Gadolinium can be administered intravenously to highlight active inflammatory lesions. CSF can be obtained by lumbar puncture and can be used to measure CNS levels of inflammation, mainly oligoclonal bands of IgG by electrophoresis, and cytokines IL17, IL8, IL1b and T cells. Brain responses can be examined using visual and sensory evoked potentials. 
     Amyotrophic lateral sclerosis (ALS) is a heterogeneous condition involving neuronal cell death. Symptoms of ALS include muscle stiffness and/or muscle twitching with gradual progression to muscle weakness and wasting. Patients with ALS have difficulty speaking, swallowing and eventually breathing. There are currently no definitive diagnostic tests for ALS and the majority of clinical testing is used to rule out other diseases. Often electromyography and nerve conduction velocity testing are used. Magnetic Resonance Imaging is often indeterminate with ALS patients. The disease presents symptoms that include muscle stiffness and twitching in a single limb involving upper or lower motor neurons. 
     Therapeutic inhibition of granulocyte proteases by sivelestat has been proposed (WO2011100567, incorporated by reference herein in its entirety.). Due to Sivelestat&#39;s low potency and therapeutic efficacy, however, more improved treatment regimens are needed for neuroinflammatory diseases associated with significant granulocyte involvement. 
     SUMMARY OF THE INVENTION 
     The present invention relates to the use of serpins, including A1AT, its derivatives and analogs thereof, in the prevention or treatment of neuroinflammatory diseases. In particular embodiments, the invention relates to the combination of A1AT and methylprednisolone. The present invention further relates to methods administering said A1AT combination. 
     Thus, the invention provides a method of treating an inflammatory condition in a subject, comprising administering a serpin protein and administering methylprednisolone. In a preferred embodiment, the serpin protein and methylprednisolone are administered simultaneously. 
     In other embodiments, the inflammatory condition is neuromyelitis optica (NMO), multiple sclerosis (MS) or amyotrophic lateral sclerosis (ALS). 
     In some embodiments, the serpin protein has at least a 90% sequence identity to SEQ ID NO:1 and has alpha-1 antitrypsin (A1AT) activity. In a preferred embodiment, the serpin protein has the sequence of SEQ ID NO:1. In another embodiment, the serpin protein is encoded by a nucleic acid that has at least a 90% sequence identity to SEQ ID NO:2 and wherein said serpin protein has alpha-1 antitrypsin (A1AT) activity. In a preferred embodiment, the serpin protein is encoded by a nucleic acid that has the sequence of SEQ ID NO:2. 
     The invention provides a method of treating an inflammatory condition in a subject, comprising administering a nucleic acid that encodes a serpin protein and administering methylprednisolone. In some embodiments, the inflammatory condition is neuromyelitis optica (NMO), multiple sclerosis (MS), or amyotrophic lateral sclerosis (ALS). 
     In some embodiments, the nucleic acid encodes a protein having at least a 90% sequence identity to SEQ ID NO:1 and has alpha-1 antitrypsin (A1AT) activity. In a preferred embodiment, the nucleic acid encodes a protein having the sequence of SEQ ID NO:1. In other embodiments, the nucleic acid has at least a 90% sequence identity to SEQ ID NO:2 and the serpin protein has alpha-1 antitrypsin (A1AT) activity. In a preferred embodiment, the nucleic acid has the sequence of SEQ ID NO:2. In other embodiments, the nucleic acid is administered by a route selected from the group consisting of transfected autologous patient cells, viral vectors, and naked nucleic acid preparations. 
     The invention provides a method of treating an inflammatory condition in a subject, comprising increasing the expression of an endogenous serpin protein and administering methylprednisolone. In other embodiments, the inflammatory condition is neuromyelitis optica (NMO), multiple sclerosis (MS), or amyotrophic lateral sclerosis (ALS). 
     In some embodiments, the endogenous serpin protein has at least a 90% sequence identity to SEQ ID NO:1 and has alpha-1 antitrypsin (A1AT) activity. In a preferred embodiment, the endogenous serpin protein has the sequence of SEQ ID NO:1. In other embodiments, the endogenous serpin protein is encoded by a nucleic acid that has at least a 90% sequence identity to SEQ ID NO:2 and wherein the serpin protein has alpha-1 antitrypsin (A1AT) activity. In a preferred embodiment, the endogenous serpin protein is encoded by a nucleic acid that has the sequence of SEQ ID NO:2. In other embodiments, the increase in serpin expression is accomplished using a technology selected from the group consisting of zinc finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs), and clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9. 
     The invention provides a pharmaceutical composition, comprising a serpin protein and methylprednisolone. In some embodiments, the serpin protein within the pharmaceutical composition has at least a 90% sequence identity to SEQ ID NO:1 and has alpha-1 antitrypsin (A1AT) activity. In a preferred embodiment, the serpin protein has the sequence of SEQ ID NO:1. In other embodiments, the serpin protein is encoded by a nucleic acid that has at least a 90% sequence identity to SEQ ID NO:2 and wherein the serpin protein has alpha-1 antitrypsin (A1AT) activity. In a preferred embodiment, the serpin protein within the pharmaceutical composition is encoded by a nucleic acid that has the sequence of SEQ ID NO:2. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         FIG. 1  shows A1AT treatment of Neuromyelitis Optica (NMO) induced by the adoptive transfer of Th17 Experimental Autoimmune Encephalomyelitis (EAE) cells to C57BL/6 mice. 
         FIG. 2  shows that A1AT treatment reduced the NMO disease score compared to PBS (control) and was superior to Sivelestat at all days of overt signs of disease as well as delay onset of disease. 
         FIG. 3  shows mean NMO disease scores are reduced by A1AT+Mpred treatment when compared to no treatment (PBS) or either treatment alone. The data represent 10 recipient mice per cohort in a blinded study and is expressed as the mean disease score+/−SEM. 
         FIG. 4  shows that A1AT+Mpred resulted in less body weight loss than either treatment alone. Ten recipient mice per cohort were used in this blinded study. The graph shows mean body weight as a percentage of the value measured at day 0+/−SEM. 
         FIG. 5A  shows that A1AT alone and A1AT+Mpred decreased the inflammatory cytokine IL-17A when compared to PBS and Mpred alone. 
         FIG. 5B  shows that A1AT alone and A1AT+Mpred decreased the inflammatory cytokine IFN-γ when compared to Mpred alone. 
         FIG. 5C  shows that all treatments increased IL-6 compared to PBS. A1AT+Mpred, however, showed the most significant reduction. 
         FIG. 5D  shows that IL-2 levels were higher without antigenic restimulation (0 MOG peptide) when treated with A1AT alone or A1AT+Mpred when compared to Mpred alone. 
     
    
    
     DETAILED DESCRIPTION OF THE INVENTION 
     The invention provides for the treatment or prevention of neuroinflammatory or neurodegenerative diseases with the combination of a serpin and another anti-inflammatory therapeutic compound. In particular embodiments, the neuroinflammatory condition is neuromyelitis optica (NMO), multiple sclerosis (MS), or amyotrophic lateral sclerosis (ALS). In other embodiments, the disease is associated with abnormal levels of Th17, CCR6 or IL8. In yet other embodiments, the Serpin is alpha-1 antitrypsin (A1AT). In other embodiments, the anti-inflammatory compound is methylprednisolone. In yet other embodiments of the invention, the therapeutic combinations disclosed herein are administered following diagnosis of a neuroinflammatory or neurodegenerative disease using a diagnostic test that measures circulating IL17, CCR6, IL8, anti-aquaporin 4 antibodies, Kir4 antibodies, neutrophil elastase or A1AT levels. 
     In describing and claiming one or more embodiments of the present invention, the following terminology will be used in accordance with the definitions described below: 
     The singular form “a”, “an”, and “the” includes plural references unless indicated otherwise. 
     The term “absorption” is the movement of a drug into the bloodstream. A drug needs to be introduced via some route of administration. For example, drugs of the invention may be delivered by oral, buccal, topical, dermal, inhalation, nasal, subcutaneous, intramuscular, or intravenous route or by any other route known in the pharmaceutical arts. Exemplary dosage forms include a solution, emulsion, inhalable powder, suspension, tablet, patch, capsule or other liquid. 
     “Amyotrophic lateral sclerosis” (ALS) as used herein includes, without limitation, a heterogeneous condition involving neuronal cell death. Symptoms of ALS include muscle stiffness and/or muscle twitching with gradual progression to muscle weakness and wasting. Patients with ALS have difficulty speaking, swallowing and eventually breathing. 
     A “clinician” or “medical researcher” or “veterinarian” as used herein, can include, without limitation, doctors, nurses, physician assistants, lab technicians, research scientists, clerical workers employed by the same, or any person involved in determining, diagnosing, aiding in the diagnosis or influencing the course of treatment for the individual. 
     An “effective amount” refers to an amount of therapeutic compound that is effective, at dosages and for periods of time necessary, to achieve the desired therapeutic or prophylactic result. A “therapeutically effective amount” of a therapeutic compound may vary according to factors such as the disease state, age, sex, and weight of the individual. A therapeutically effective amount may be measured, for example, by improved survival rate, more rapid recovery, or amelioration, improvement or elimination of symptoms, or other acceptable biomarkers or surrogate markers. A “therapeutically effective amount” is also one in which any toxic or detrimental effects of the therapeutic compound are outweighed by the therapeutically beneficial effects. A “prophylactically effective amount” refers to an amount of therapeutic compound that is effective, at dosages and for periods of time necessary, to achieve the desired prophylactic result. Typically, but not necessarily, since a prophylactic dose is used in subjects prior to or at an earlier stage of disease, the prophylactically effective amount will be less than the therapeutically effective amount. 
     “Homologs” are bioactive molecules that are similar to a reference molecule at the nucleotide sequence, peptide sequence, functional, or structural level. Homologs may include sequence derivatives that share a certain percent identity with the reference sequence. Thus, in one embodiment, homologous or derivative sequences share at least a 70 percent sequence identity. In a preferred embodiment, homologous or derivative sequences share at least an 80 or 85 percent sequence identity. In a more preferred embodiment, homologous or derivative sequences share at least an 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99 percent sequence identity. Homologous or derivative nucleic acid sequences may also be defined by their ability to remain bound to a reference nucleic acid sequence under high stringency hybridization conditions. Homologs having a structural or functional similarity to a reference molecule may be chemical derivatives of the reference molecule. Methods of detecting, generating, and screening for structural and functional homologs as well as derivatives are known in the art. 
     “Hybridization” generally depends on the ability of denatured DNA to reanneal when complementary strands are present in an environment below their melting temperature. The higher the degree of desired homology between the probe and hybridizable sequence, the higher the relative temperature that can be used. As a result, it follows that higher relative temperatures would tend to make the reaction conditions more stringent, while lower temperatures less so. For additional details and explanation of stringency of hybridization reactions, see Ausubel et al, Current Protocols in Molecular Biology, Wiley Interscience Publishers (1995). 
     An “individual,” “subject” or “patient” is a vertebrate. In certain embodiments, the vertebrate is a mammal. Mammals include, but are not limited to, primates (including human and non-human primates), rodents (e.g., mice, hamsters, guinea pigs, and rats), farm animals, sport animals, and pets (e.g. dogs and cats). In certain embodiments, a mammal is a human. A “control subject” may refer to a healthy subject who has not been diagnosed as having a disease, dysfunction, or condition that has been identified in an individual, subject, or patient. The control subject does not suffer from any sign or symptom associated with the disease, dysfunction, or condition. Alternatively, a control subject may be a sick subject that does not receive the therapeutic drug, another drug, or a lower dose of the drug. 
     A “medicament” is an active drug that has been manufactured for the treatment of a disease, disorder, or condition. 
     “Morpholinos” are synthetic molecules that are non-natural variants of natural nucleic acids that utilize a phosphorodiamidate linkage, described in U.S. Pat. No. 8,076,476, incorporated by reference herein in its entirety. 
     “Multiple sclerosis” (MS) as used herein can include without limitation a heterogeneous condition consisting of recurrent and simultaneous inflammatory lesions of the spinal cord and brain causing demyelination of nerves in the central nervous system. 
     “Neuromyelitis optica” (NMO) as used herein can include without limitation a heterogeneous condition consisting of recurrent and simultaneous inflammation and demyelination of the optic nerve (optic neuritis) and spinal cord (myelitis). At least two different causes are known for NMO including the presence of autoantibodies against aquaporin 4 and aberrant astrocyte activity. An increasing body of evidence also supports the contribution of Th17 cells and a role of granulocytic release at the site of inflammation. 
     “Neuromyelitis optica” (NMO) as used herein can include without limitation a heterogeneous condition consisting of acute, recurrent or chronic/progressive inflammation or demyelination of the optic nerve (optic neuritis) or spinal cord (myelitis). 
     “Nucleic acids” are any of a group of macromolecules, either DNA, RNA, or variants thereof, that carry genetic information that may direct cellular functions. Nucleic acids may have enzyme-like activity (for instance ribozymes) or may be used to inhibit gene expression in a subject (for instance RNAi). The nucleic acids used in the inventions described herein may be single-stranded, double-stranded, linear or circular. The inventions further incorporate the use of nucleic acid variants including, but not limited to, aptamers, PNA, Morpholino, or other non-natural variants of nucleic acids. By way of example, nucleic acids useful for the invention are described in U.S. Pat. No. 8,076,476, incorporated by reference herein in its entirety. 
     “Patient response” or “response” can be assessed using any endpoint indicating a benefit to the patient, including, without limitation, (1) inhibition, to some extent, of disease progression, including stabilization, slowing down and complete arrest; (2) reduction in the number of disease episodes and/or symptoms; (3) inhibition (i.e., reduction, slowing down or complete stopping) of a disease cell infiltration into adjacent peripheral organs and/or tissues; (4) inhibition (i.e. reduction, slowing down or complete stopping) of disease spread; (5) decrease of an autoimmune condition; (6) favorable change in the expression of a biomarker associated with the disorder; (7) relief, to some extent, of one or more symptoms associated with a disorder; (8) increase in the length of disease-free presentation following treatment; or (9) decreased mortality at a given point of time following treatment. 
     As used herein, the term “peptide” is any peptide comprising two or more amino acids. The term peptide includes short peptides (e.g., peptides comprising between 2-14 amino acids), medium length peptides (15-50) or long chain peptides (e.g., proteins). The terms peptide, medium length peptide and protein may be used interchangeably herein. As used herein, the term “peptide” is interpreted to mean a polymer composed of amino acid residues, related naturally occurring structural variants, and synthetic non-naturally occurring analogs thereof linked via peptide bonds, related naturally-occurring structural variants, and synthetic non-naturally occurring analogs thereof. Synthetic peptides can be synthesized, for example, using an automated peptide synthesizer. Peptides can also be synthesized by other means such as by cells, bacteria, yeast or other living organisms. Peptides may contain amino acids other than the 20 gene-encoded amino acids. Peptides include those modified either by natural processes, such as processing and other post-translational modifications, but also by chemical modification techniques. Such modifications are well described in basic texts and in more detailed monographs, and are well-known to those of skill in the art. Modifications can occur anywhere in a peptide, including the peptide backbone, the amino acid side chains, and the amino or carboxyl termini. 
     As used herein, a “pharmaceutically acceptable carrier” or “therapeutic effective carrier” is aqueous or nonaqueous (solid), for example alcoholic or oleaginous, or a mixture thereof, and can contain a surfactant, emollient, lubricant, stabilizer, dye, perfume, preservative, acid or base for adjustment of pH, a solvent, emulsifier, gelling agent, moisturizer, stabilizer, wetting agent, time release agent, humectant, or other component commonly included in a particular form of pharmaceutical composition. Pharmaceutically acceptable carriers are well known in the art and include, for example, aqueous solutions such as water or physiologically buffered saline or other solvents or vehicles such as glycols, glycerol, and oils such as olive oil or injectable organic esters. A pharmaceutically acceptable carrier can contain physiologically acceptable compounds that act, for example, to stabilize or to increase the absorption of specific modulator(s), for example, carbohydrates, such as glucose, sucrose or dextrans, antioxidants such as ascorbic acid or glutathione, chelating agents, low molecular weight proteins or other stabilizers or excipients. 
     The term “pharmaceutical dose” or “pharmaceutical dosage form,” refers to physically discrete units suitable as unitary dosages for humans and other mammals, each unit comprising a predetermined quantity of agents in an amount calculated sufficient to produce the desired effect in association with an acceptable diluent, carrier, or vehicle of a formulation. The specifications for the unit dosage forms may depend on the particular serpin form employed, the effect to be achieved, the route of administration and the pharmacodynamics associated with the mammal. 
     “PNA” refers to peptide nucleic acids with a chemical structure similar to DNA or RNA. Peptide bonds are used to link the nucleotides or nucleosides together. 
     “Stringency” of hybridization reactions is readily determinable by one of ordinary skill in the art, and generally is an empirical calculation dependent upon probe length, washing temperature, and salt concentration. In general, longer probes require higher temperatures for proper annealing, while shorter probes need lower temperatures. 
     “Stringent conditions” or “high stringency conditions”, as defined herein, can be identified by those that: (1) employ low ionic strength and high temperature for washing, for example 0.015 M sodium chloride/0.0015 M sodium citrate/0.1% sodium dodecyl sulfate at 50° C.; (2) employ during hybridization a denaturing agent, such as formamide, for example, 50% (v/v) formamide with 0.1% bovine serum albumin/0.1% Ficoll/0.1% polyvinylpyrrolidone/50 mM sodium phosphate buffer at pH 6.5 with 750 mM sodium chloride, 75 mM sodium citrate at 42° C.; or (3) overnight hybridization in a solution that employs 50% formamide, 5×SSC (0.75 M NaCl, 0.075 M sodium citrate), 50 mM sodium phosphate (pH 6.8), 0.1% sodium pyrophosphate, 5×Denhardt&#39;s solution, sonicated salmon sperm DNA (50 μl/ml), 0.1% SDS, and 10% dextran sulfate at 42° C., with a 10 minute wash at 42° C. in 0.2×SSC (sodium chloride/sodium citrate) followed by a 10 minute high-stringency wash consisting of 0.1×SSC containing EDTA at 55° C. 
     As used herein, “treatment” refers to clinical intervention in an attempt to alter the natural course of the individual or cell being treated, and can be performed before or during the course of clinical pathology. Desirable effects of treatment include preventing the occurrence or recurrence of a disease or a condition or symptom thereof, alleviating a condition or symptom of the disease, diminishing any direct or indirect pathological consequences of the disease, decreasing the rate of disease progression, ameliorating or palliating the disease state, and achieving remission or improved prognosis. In some embodiments, methods and compositions of the invention are useful in attempts to delay development of a disease or disorder. 
     It is intended that every maximum numerical limitation given throughout this specification includes every lower numerical limitation, as if such lower numerical limitations were expressly written herein. Every minimum numerical limitation given throughout this specification will include every higher numerical limitation, as if such higher numerical limitations were expressly written herein. Every numerical range given throughout this specification will include every narrower numerical range that falls within such broader numerical range, as if such narrower numerical ranges were all expressly written herein. 
     In some embodiments, serpins and the other anti-inflammatory therapeutic compounds work synergistically. A person of skill in the art would appreciate that the synergistic activities may be established at appropriate fixed-dose ratios for efficacy against granulocyte-associated neuroinflammatory diseases. This may be determined by varying the amounts of two agents administered to appropriate animal models of inflammatory disease. The model may reflect either an active disease (following disease onset) or an early time point representative of pre-clinical disease. The effect on disease activity or progression is measured. 
     In other embodiments, the effects of varying amounts of the two agents may be determined in a cellular response mediating inflammation that may be involved in the pathogenesis of the disease. In other embodiments, the effects of varying amounts of the two agents in various formulations is determined by measuring enzymatic activity in vitro. 
     The presence, absence or degree of associated disease pathology or inflammatory markers such as granulocyte counts (in situ or circulating), protease activity, Th17 effector cell counts, plasma cell counts, CCR6, IL8, IL17, IL23, endogenous serpin, anti-aquaporin 4 antibodies, anti-Kir4 antibody levels can be used to evaluate efficacy. Successful compositions with the appropriate determined dose are selected that reduce said inflammatory markers, ameliorate disease symptoms or are tolerated by test animals. 
     The invention provides that the pharmaceutical compositions disclosed herein are formulated into solid, semi-solid, pressed powder, powder, liquid, gel, suspension, emulsion, or gaseous forms. In other embodiments, the pharmaceutical compositions are formulated into liquids, syrups, concentrates, tablets, capsules, caplets, powders, rapid melts, thin strips, granules, ointments, crémes, solutions, suspensions, emulsions, suppositories, injections, inhalants, gels, crystals and aerosols. 
     Methods for Treating Neuroinflammatory Diseases 
     Individuals and other mammals at increased risk for development of a granulocyte-mediated neuroinflammatory disease, with early-stage of disease, or with established disease, may be treated with a clinically effective amount of any of the compositions disclosed herein. In some embodiments, the pharmaceutical compositions described herein prevent the development of disease, prevent the progression of disease, or to prevent the progression of the symptoms or signs of disease. 
     Thus, disclosed herein are methods for treating a patient with a neurodegenerative disease. Also disclosed herein are methods for treating a patient with symptoms consistent with neurodegenerative disease. Persons of skill in the art may determine preferred routes of administering the pharmaceutical compositions described herein, the corresponding dosage form, dose amount, and the dosing regimen (i.e., the frequency of dosing). 
     In some embodiments, the composition may be delivered in multi-dosing formats whereby the compositions are administered several times a week, once a day, twice a day, three times a day or more to achieve the appropriate therapeutic level. Other variables to consider include the specific serpin, inflammatory markers that are measured, the disease symptoms to be affected, the specific neuroinflammatory disease, the other anti-inflammatory therapeutic agent involved and its pharmacokinetic profile, and the specific individual involved. 
     In other embodiments, the frequency of administration may be once a month, once a week, once a day, or on an as-needed basis. Frequency of administration may be dependent on the identity and concentration of serpin in the composition or the disease risk assessment, disease severity, test results, clinician preference, or pharmaceutical formulation. 
     Polynucleotides Encoding Serpins 
     Some embodiments of the invention provide serpin compositions for use as treatment for neuroinflammatory diseases. Said compositions may be administered on a daily, weekly, monthly, yearly or on an as-needed basis to reduce symptoms of disease or to reduce disease progression. In some embodiments, the serpin is A1AT. 
     The invention provides nucleic acids encoding a serpin protein. The nucleic acids may be DNA molecules, RNA molecules, aptamers (single-stranded or double-stranded), DNA or RNA oligonucleotides, larger DNA molecules that are linear or circular, oligonucleotides that are used for RNA interference (RNAi), variations of DNA such as substitution of DNA/RNA hybrid molecules, synthetic DNA-like molecules such as PNA or other nucleic acid derivative molecules (see WO07/035922, incorporated by reference herein in its entirety). In another embodiment, the therapeutic compound is composed of nuclease-resistant DNA or RNA oligonucleotides. In a preferred embodiment, nuclease-resistant DNA oligonucleotides are Morpholinos, (i.e. phosphorodiamidate analogs of nucleic acids that bind to nucleic acids in a sequence-specific manner, Sarepta Therapeutics, Cambridge Mass.). 
     In some embodiments, the serpin nucleic acids of the invention are synthesized using methods well-known in the art. In one embodiment, the nucleic acids are generated by enzymes. In exemplary embodiments, the enzymes may include DNA polymerases, RNA polymerases, ligases, and DNA repair enzymes. In another preferred embodiment, the nucleic acids are generated by a polymerase chain reaction (PCR) protocol. See, e.g. U.S. Pat. No. 4,683,195. In other embodiments, the nucleic acids are chemically synthesized using techniques well-known in the art. Typically, solid-phase nucleic acid synthesizers are used. Exemplary chemistries include phosphodiester synthesis, phosphotriester synthesis, and phosphite triester synthesis. See, e.g., Reese, Colin B. (2005). “Oligo- and poly-nucleotides: 50 years of chemical synthesis”.  Organic  &amp;  Biomolecular Chemistry  3 (21): 3851. The skilled artisan would understand that any techniques for synthesizing the nucleic acids and derivatives disclosed herein may be used. 
     In some embodiments, the serpin compositions of the invention may include A1AT. In a preferred embodiment, a nucleic acid containing at least about a 90% sequence identity to the human gene encoding A1AT precursor protein (SEQ ID NO:1) is delivered to a patient having neuroinflammatory symptoms consistent with NMO, MS and ALS. In another preferred embodiment, the A1AT composition may include a nucleic acid containing a sequence derived from A1AT mRNA. In another preferred embodiment, mRNA encoding human A1AT precursor protein is delivered to a patient having neuroinflammatory symptoms consistent with NMO, MS and ALS. In more preferred embodiments, the invention contemplates nucleic acids that hybridize with high stringency to a nucleic acid encoding A1AT (e.g. SEQ ID NO:2). Other preferred embodiments, nucleic acids encoding serpins are delivered to an individual via a viral vector, as a naked nucleic acid, or in a transformed cell. 
     In some embodiments, nucleic acids encoding serpins are administered to a patient in a cell-dependent manner. In preferred embodiments, the serpins or nucleic acids encoding them are delivered using transfected autologous patient cells. In other embodiments, serpins are delivered by intrathecal, intramuscular, intravascular, subcutaneous, intracranial, intraocular injection or inhaled routes. In more preferred embodiments, the nucleic acid encodes an A1AT protein having at least about a 90% sequence identity to SEQ ID NO:1. In more preferred embodiments, the serpin is an A1AT protein encoded by a nucleic acid that hybridize with high stringency to a nucleic acid encoding A1AT (e.g. SEQ ID NO:2). 
     The nucleic acids of the invention encode serpins that retain serpin functional activity. In preferred embodiments, the nucleic acids of the invention encode proteins that retain A1AT functional activity. 
     The invention provides non-viral serpin liquid or powder formulations. In some embodiments, the serpin is A1AT. In preferred embodiments, the serpin dose range is based on the selection of serpin form and associated properties. For example, plasmid backbone, promoter strength, and size, etc. In preferred embodiments, the copy number ranges from about 500 mM to about 10 pM per dose, depending on the use. Other embodiments comprise a serpin from about 500 mM to about 1 mM per dose. Further embodiments comprise a serpin from about 500 μM to about 1 μM per dose. Yet other embodiments comprise a serpin from about 10 μM to about 10 nM per dose. Further embodiments comprise a serpin from about 800 nM to about 10 pM per dose. 
     The invention provides viral serpin liquid or powder formulations. In preferred embodiments, the serpin is A1AT. Serpin dose can range based on selection of virus. Generally recommended are dose ranges from about 5×10 9  PFU/mL to about 1×10 3  PFU/mL per dose, depending on the use. Some compositions may comprise serpins from about 5×10 9  PFU/mL to about 1×10 8  PFU/mL per dose. Some compositions may comprise serpins from about 0.9×10 8  PFU/mL to about 1×10 6  PFU/mL per dose. Other compositions may comprise serpins from about 0.9×10 6  PFU/mL to about 1×10 5  PFU/mL per dose. Yet other compositions may comprise serpins from about 0.9×10 5  PFU/mL to about 1×10 3  PFU/mL per dose. 
     Periodicity of dosing may vary based on patient needs. In some embodiments, serpins are administered on a weekly or monthly basis. One advantage of a genetic approach is that serpin levels can be sustained longer than recombinant and human-derived purified forms. 
     Gene therapies and viral vectors that introduce DNA, RNA, transgenes, or other nucleic acid sequences to individuals are known in the art. (See, e.g., US20160046961; US20160040150; USRE045847; US20150218585; US20150167003; and U.S. Pat. No. 9,023,646; Rosenberg et al.  N Engl. J. Med.  323: 570-8 (1990); Baltimore et al., Science 348: 36-8 (2015). The foregoing references are incorporated by reference in their entirety.) 
     The invention contemplates providing serpins using recombinant DNA techniques that result in addition or increased expression of a serpin. Exemplary technologies include homologous recombination, knock-in, ZFNs (zinc finger nucleases), TALENs (transcription activator-like effector nucleases), CRISPR (clustered regularly interspaced short palindromic repeats)/Cas9, and other site-specific nuclease technologies. These techniques enable double-strand DNA breaks at desired locus sites. These controlled double-strand breaks promote homologous recombination at the specific locus sites. This process relies on targeting specific sequences of nucleic acid molecules, such as chromosomes, with endonucleases that recognize and bind to the sequences and induce a double-stranded break in the nucleic acid molecule. The double-strand break is repaired either by an error-prone non-homologous end-joining (NHEJ) or by homologous recombination (HR). (See, e.g., WO2016025759, WO2015191693, US20160046961, US20160046960, US20160046952, US20160046915, and U.S. Pat. No. 9,260,752, each of which are incorporated by reference herein in their entirety.) 
     Serpin Proteins 
     The invention provides therapeutic serpin peptides as disclosed herein. In one embodiment, the Serpin is a protein that has at least a 90% sequence identity to SEQ ID NO:1 and has A1AT activity. In preferred embodiments, the Serpin has the sequence of SEQ ID NO:1. 
     The terms “protein” and “peptide” refer to molecules that include a string of amino acids. The amino acids in the peptides of the invention may be naturally-occurring or non-naturally-occurring. The peptides of the invention may be synthesized chemically or biologically, and can include cysteine-rich peptides, circular peptides, stapled peptides, peptides that include D- or L-amino acids and mixtures thereof, peptidomimetics, peptide-nucleic acids (PNAs), and combinations thereof. 
     The invention provides recombinant or synthesized serpin compositions. In preferred embodiments, recombinant serpin compositions comprise cell-derived, purified serpins. In other preferred embodiments, human serpin precursor proteins are purified from an in vitro transfected cell culture. 
     In some embodiments, synthetic serpins are synthesized using protein chemistry known in the art. In preferred embodiments, the synthetic proteins are synthesized using liquid-phase or solid-phase peptide synthesis techniques. 
     Also contemplated within the scope of embodiments described herein are serpin peptides that are branched or cyclic, with or without branching. Cyclic, branched and branched circular peptides result from post-translational natural processes and are also made by suitable synthetic methods. In some embodiments, any peptide product described herein comprises a peptide analog described above that is then covalently attached to an alkyl-glycoside surfactant moiety. 
     Other embodiments include serpin peptide chains that are comprised of natural and unnatural amino acids or analogs of natural amino acids. As used herein, peptide and/or protein “analogs” comprise non-natural amino acids based on natural amino acids, such as tyrosine analogs, which includes para-substituted tyrosines, ortho-substituted tyrosines, and meta-substituted tyrosines, wherein the substituent on the tyrosine comprises an acetyl group, a benzoyl group, an amino group, a hydrazine, an hydroxyamine, a thiol group, a carboxy group, a methyl group, an isopropyl group, a C2-C20 straight chain or branched hydrocarbon, a saturated or unsaturated hydrocarbon, an O-methyl group, a polyether group, a halogen, a nitro group, or the like. 
     Additional embodiments include serpin peptide chains having modified amino acids. 
     Examples include acylated amino acids at the ε-position of Lysine, amino acids with fatty acids such as octanoic, decanoic, dodecanoic, tetradecanoic, hexadecanoic, octadecanoic, 3-phenylpropanoic acids and the like, or with saturated or unsaturated alkyl chains. (Zhang, L. and Bulaj, G (2012) Curr Med Chem 19: 1602-1618, incorporated herein by reference in its entirety). 
     The invention further contemplates serpin peptide chains comprising natural and unnatural amino acids or analogs of natural amino acids. In some embodiments, peptide or protein “analogs” comprise non-natural amino acids based on natural amino acids, such as tyrosine analogs, which includes para-substituted tyrosines, ortho-substituted tyrosines, and meta-substituted tyrosines, wherein the substituent on the tyrosine comprises an acetyl group, a benzoyl group, an amino group, a hydrazine, an hydroxyamine, a thiol group, a carboxy group, a methyl group, an isopropyl group, a C2-C20 straight chain or branched hydrocarbon, a saturated or unsaturated hydrocarbon, an O-methyl group, a polyether group, a halogen, a nitro group, or the like. Examples of Tyr analogs include 2,4-dimethyl-tyrosine (Dmt), 2,4-diethyl-tyrosine, O-4-allyl-tyrosine, 4-propyl-tyrosine, Ca-methyl-tyrosine and the like. Examples of lysine analogs include ornithine (Orn), homo-lysine, Ca-methyl-lysine (CMeLys), and the like. Examples of phenylalanine analogs include, but are not limited to, meta-substituted phenylalanines, wherein the substituent comprises a methoxy group, a C1-C20 alkyl group, for example a methyl group, an allyl group, an acetyl group, or the like. Specific examples include, but are not limited to, 2,4,6-trimethyl-L-phenylalanine (Tmp), O-methyl-tyrosine, 3-(2-naphthyl)alanine (Nal(2)), 3-(1-naphthyl)alanine (Nal(1)), 3-methyl-phenylalanine, 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid (Tic), fluorinated phenylalanines, isopropyl-phenylalanine, p-azido-phenylalanine, p-acyl-phenylalanine, p-benzoyl-phenylalanine, p-iodo-phenylalanine, p-bromophenylalanine, p-amino-phenylalanine, and isopropyl-phenylalanine, and the like. 
     Also contemplated within the scope of embodiments are therapeutic peptide chains containing nonstandard or unnatural amino acids known to the art, for example, C-alpha-disubstituted amino acids such as Aib, Ca-diethylglycine (Deg), aminocyclopentane-1-carboxylic acid (Ac4c), aminocyclopentane-1-carboxylic acid (Ac5c), and the like. Such amino acids frequently lead to a restrained structure, often biased toward an alpha helical structure (Kaul, R. and Balaram, P. (1999) Bioorg Med Chem 7: 105-117, incorporated herein by reference in its entirety). Additional examples of such unnatural amino acids useful in analog design are homo-arginine (Har) and the like. Substitution of reduced amide bonds in certain instances leads to improved protection from enzymatic destruction or alters receptor binding. By way of example, incorporation of a Tic-Phe dipeptide unit with a reduced amide bond between the residues (designated as Tic-F[CH2-NH]̂-Phe) reduces enzymatic degradation. 
     In some embodiments, modifications at the amino or carboxyl terminus may optionally be introduced into the present peptides or proteins (Nestor, J. J., Jr. (2009) Current Medicinal Chemistry 16: 4399-4418). For example, the present peptides or proteins can be truncated or acylated on the N-terminus (Gourlet, P., et al. (1998) Eur J Pharmacol 354: 105-1 1 1, Gozes, I. and Furman, S. (2003) Curr Pharm Des 9: 483-494), the contents of which is incorporated herein by reference in their entirety). Other modifications to the N-terminus of peptides or proteins, such as deletions or incorporation of D-amino acids such as D-Phe result in potent and long acting agonists or antagonists when substituted with the modifications described herein such as long chain alkyl glycosides. 
     Thus, the invention provides serpin compound analogs wherein the native therapeutic compound is modified by acetylation, acylation, PEGylation, ADP-ribosylation, amidation, covalent attachment of a lipid or lipid derivative, covalent attachment of phosphotidylinositol, cross-linking, cyclization, disulfide bond formation, demethylation, formation of covalent cross-link formation of cysteine, formation of pyroglutamate, formylation, gamma-carboxylation, glycosylation, GPI anchor formation, hydroxylation, iodination, methylation, myristoylation, oxidation, proteolytic processing, phosphorylation, prenylation, racemization, glycosylation, lipid attachment, sulfation, gamma-carboxylation of glutamic acid residues, hydroxylation and ADP-ribosylation, selenoylation, sulfation, transfer-RNA mediated addition of amino acids to proteins, such as arginylation, and ubiquitination. See, for instance, (Nestor, J. J., Jr. (2007) Comprehensive Medicinal Chemistry II 2: 573-601, Nestor, J. J., Jr. (2009) Current Medicinal Chemistry 16: 4399-4418, Uy, R. and Wold, F. (1977) Science 198:890-6, Seifter, S. and Englard, S. (1990) Methods Enzymol 182: 626-646, Rattan, S. I., et al. (1992) Ann NY Acad Sci 663: 48-62). The foregoing references are incorporated by reference in their entirety. 
     Glycosylated serpin peptides may be prepared using conventional Fmoc chemistry and solid phase peptide synthesis techniques, e.g., on resin, where the desired protected glycoamino acids are prepared prior to peptide synthesis and then introduced into the peptide chain at the desired position during peptide synthesis. Thus, the therapeutic peptide polymer conjugates may be conjugated in vitro. The glycosylation may occur before deprotection. Preparation of amino acid glycosides is described in U.S. Pat. No. 5,767,254, WO 2005/097158, and Doores, K., et al., Chem. Commun., 1401-1403, 2006, which are incorporated herein by reference in their entirety. For example, alpha and beta selective glycosylations of serine and threonine residues are carried out using the Koenigs-Knorr reaction and Lemieux&#39;s in situ anomerization methodology with Schiff base intermediates. Deprotection of the Schiff base glycoside is then carried out using mildly acidic conditions or hydrogenolysis. A composition, comprising a glycosylated therapeutic peptide conjugate is made by stepwise solid phase peptide synthesis involving contacting a growing peptide chain with protected amino acids in a stepwise manner, wherein at least one of the protected amino acids is glycosylated, followed by water-soluble polymer conjugation. Such compositions may have a purity of at least 95%, at least 97%, or at least 98%, of a single species of the glycosylated and conjugated therapeutic peptide. 
     Monosaccharides that may by used for introduction at one or more amino acid residues of the therapeutic peptides defined and/or disclosed herein include glucose (dextrose), fructose, galactose, and ribose. Additional monosaccharides suitable for use include glyceraldehydes, dihydroxyacetone, erythrose, threose, erythrulose, arabinose, lyxose, xylose, ribulose, xylulose, allose, altrose, mannose, N-Acetylneuraminic acid, fucose, N-Acetylgalactosamine, and N-Acetylglucosamine, as well as others. Glycosides, such as mono-, di-, and trisaccharides for use in modifying a therapeutic peptide, one or more amino acid residues of the therapeutic peptides defined and/or disclosed herein include sucrose, lactose, maltose, trehalose, melibiose, and cellobiose, among others. Trisaccharides include acarbose, raffinose, and melezitose. 
     In other embodiments, the nucleic acids of the invention may be expressed in microorganisms. Promoters for expressing genes of interest are known in the art. In some embodiments, the expression vectors of the invention may have promoters, transcription terminators, or selectable markers. Either inducible or constitutive promoters are contemplated by the invention. 
     In a preferred embodiment, the nucleic acids of the invention are expressed in bacterial systems because of their low cost, high productivity, and rapid use. Thus, the nucleic acids are expressed in, for example,  Bacillus brevis, Bacillus megaterium, Bacillus subtilis, Caulobacter crescentus, Escherichia coli  and their derivatives. Exemplary promoters include the 1-arabinose inducible araBAD promoter (PBAD), the lac promoter, the 1-rhamnose inducible rhaP BAD promoter, the T7 RNA polymerase promoter, the trc and tac promoter, the lambda phage promoter pL, and the anhydrotetracycline-inducible tetA promoter/operator. 
     In some embodiments, the nucleic acids of the invention are expressed in yeast expression systems. Exemplary promoters used in yeast vectors include the promoters for 3-phosphoglycerate kinase (Hitzeman et al., J. Biol. Chem. 255:2073 ((1980)); and other glycolytic enzymes (Hess et al., J. Adv. Enzyme Res. 7:149 (1968); Holland et al., Biochemistry 17:4900 (1978)), e.g., enolase, glyceraldehyde-3-phosphate dehydrogenase, hexokinase, pyvurate decarboxylase, phosphofructokinase, glucose-6-phosphate isomerase, 3-phosphoglycerate mutase, pyruvate kinase, triosephosphate somerase, phosphoglucose isomerase, glucokinase alcohol oxidase I (AOX1), alcohol dehydrogenase 2, isocytochrome C, acid phosphatase, degradative enzymes associated with nitrogen metabolism, and the aforementioned glyceraldehyde-3-phosphate dehydrogenase, and enzymes responsible for maltose and galactose utilization. Any plasmid vector containing a yeast-compatible promoter and termination sequences, with or without an origin of replication, is suitable. Yeast expression systems are commercially available, for example, from Clontech Laboratories, Inc. (Palo Alto, Calif., e.g. pYEX 4T family of vectors for  S. cerevisiae ), Invitrogen (Carlsbad, Calif., e.g. pPICZ series Easy Select  Pichia  Expression Kit) and Stratagene (La Jolla, Calif., e.g. ESP™ Yeast Protein Expression and Purification System for  S. pombe  and pESC vectors for  S. cerevisiae ). 
     In other embodiments, the nucleic acids of the invention are expressed in mammalian expression systems. Examples of suitable mammalian promoters for use in the invention include, for example, promoters from the following genes: ubiquitin/S27a promoter of the hamster (WO 97/15664), Simian vacuolating virus 40 (SV40) early promoter, adenovirus major late promoter, mouse metallothionein-I promoter, the long terminal repeat region of Rous Sarcoma Virus (RSV), mouse mammary tumor virus promoter (MMTV), Moloney murine leukemia virus Long Terminal repeat region, and the early promoter of human Cytomegalovirus (CMV). Examples of other heterologous mammalian promoters are the actin, immunoglobulin or heat shock promoter(s). In a preferred embodiment, a yeast alcohol oxidase promoter is used. 
     In additional embodiments, promoters for use in mammalian host cells can be obtained from the genomes of viruses such as polyoma virus, fowlpox virus (UK 2,211,504 published 5 Jul. 1989), bovine papilloma virus, avian sarcoma virus, cytomegalovirus, a retrovirus, hepatitis-B virus and Simian Virus 40 (SV40). In further embodiments, heterologous mammalian promoters are used. Examples include the actin promoter, an immunoglobulin promoter, and heat-shock promoters. The early and late promoters of SV40 are conveniently obtained as an SV40 restriction fragment which also contains the SV40 viral origin of replication. Fiers et al.,  Nature  273: 113-120 (1978). The immediate early promoter of the human cytomegalovirus is conveniently obtained as a HindIII E restriction fragment. Greenaway, P. J. et al., Gene 18: 355-360 (1982). The foregoing references are incorporated by reference in their entirety. 
     In some embodiments, the nucleic acids of the invention are expressed in insect cell expression systems. Eukaryotic expression systems employing insect cell hosts may rely on either plasmid or baculoviral expression systems. The typical insect host cells are derived from the fall army worm ( Spodoptera frugiperda ). For expression of a foreign protein these cells are infected with a recombinant form of the baculovirus  Autographa californica  nuclear polyhedrosis virus which has the gene of interest expressed under the control of the viral polyhedrin promoter. Other insects infected by this virus include a cell line known commercially as “High 5” (Invitrogen) which is derived from the cabbage looper ( Trichoplusia ni ). Another baculovirus sometimes used is the  Bombyx mori  nuclear polyhedorsis virus which infect the silk worm ( Bombyx mori ). Numerous baculovirus expression systems are commercially available, for example, from Invitrogen (Bac-N-Blue™), Clontech (BacPAK™ Baculovirus Expression System), Life Technologies (BAC-TO-BAC™), Novagen (Bac Vector System™), Pharmingen and Quantum Biotechnologies). Another insect cell host is the common fruit fly,  Drosophila melanogaster , for which a transient or stable plasmid based transfection kit is offered commercially by Invitrogen (The DES™ System). 
     In some embodiments, cells are transformed with vectors that express the nucleic acids of the invention. Transformation techniques for inserting new genetic material into eukaryotic cells, including animal and plant cells, are well known. Viral vectors may be used for inserting expression cassettes into host cell genomes. Alternatively, the vectors may be transfected into the host cells. Transfection may be accomplished by calcium phosphate precipitation, electroporation, optical transfection, protoplast fusion, impalefection, and hydrodynamic delivery. 
     In preferred embodiments, the serpin nucleic acids are expressed in mammalian cell lines that are well-known in the art. Exemplary mammalian cell lines include Chinese hamster ovary cells (CHO) and Vero cells. The serpins are recovered using known biochemical and biologics manufacturing techniques. (See, e.g., Lai et al.,  Pharmaceuticals  6:579-603 (2013), incorporated by reference herein in its entirety.) 
     Examplary therapeutic Serpin family members are presented in Table 1. 
     
       
         
           
               
               
               
               
               
             
               
                 TABLE 1 
               
               
                   
               
               
                 SERPIN 
                 SOURCE 
                 SEQ ID NO 
                 DEMONSTRATED EFFECTS 
                 DOSE RANGE (per kg) 
               
               
                   
               
             
            
               
                 A1AT 
                 Human 
                 1, 2 
                 Inhibits neutrophil elastase 
                 1,000 mg to 0.5 ng; 
               
               
                 (SerpinA1) 
                   
                   
                 and other proteases 
                 500 mM to 10 pM 
               
               
                 CrmA 
                 Cowpox 
                 3, 4 
                 Suppressor of IL1 and IL18 
                 1,000 mg to 0.5 ng; 
               
               
                   
                 virus 
                   
                   
                 300 mM to 10 pM 
               
               
                 Serpin1 or 
                 
                   Arabidopsis 
                 
                 5, 6 
                 Suppressor of metacaspases 
                 2,000 mg to 10 ng; 
               
               
                 AtSerpin1 or 
                   
                   
                 and papain-like cysteine 
                 1000 mM to 50 pM 
               
               
                 Serpin-ZX 
                   
                   
                 protease 
               
               
                 SerpinB9 
                 Human 
                 7, 8 
                 Inhibits Granzyme B 
                 1,000 mg to 0.5 ng; 
               
               
                   
                   
                   
                   
                 500 mM to 10 pM 
               
               
                 SerpinA3 
                 Human 
                 9, 10, 11 
                 Inhibits cathepsin G 
                 1,000 mg to 0.5 ng; 
               
               
                   
                   
                   
                   
                 500 mM to 10 pM 
               
               
                 SerpinA4 
                 Human 
                 12-17 
                 Inhibits kallikrein 
                 1,000 mg to 0.5 ng; 
               
               
                   
                   
                   
                   
                 500 mM to 10 pM 
               
               
                 SerpinA5 
                 Human 
                 18, 19 
                 Inhibits protein C, reduces 
                 1,000 mg to 0.5 ng; 
               
               
                   
                   
                   
                 PCI in MS plaques 
                 500 mM to 10 pM 
               
               
                 SerpinA9 
                 Human 
                 20-27 
                 Inhibits B cell activation 
                 2,000 mg to 1.5 ng; 
               
               
                   
                   
                   
                   
                 700 mM to 50 pM 
               
               
                 SerpinA10 
                 Human 
                 28-31 
                 Inhibits protein Z-related 
                 1,000 mg to 0.5 ng; 
               
               
                   
                   
                   
                 protease, factors Xa and XIa 
                 500 mM to 10 pM 
               
               
                 SerpinA12 
                 Human 
                 32-35 
                 Inhibits Kallikrein-7 
                 1,000 mg to 0.5 ng; 
               
               
                   
                   
                   
                   
                 500 mM to 10 pM 
               
               
                 SerpinB1 
                 Human 
                 36, 37 
                 Inhibits neutrophil elastase 
                 1,000 mg to 0.5 ng; 
               
               
                   
                   
                   
                 and monocytes 
                 500 mM to 10 pM 
               
               
                 SerpinB6 
                 Human 
                 38-53 
                 Inhibits cathepsin G 
                 1,000 mg to 0.5 ng; 
               
               
                   
                   
                   
                   
                 500 mM to 10 pM 
               
               
                 SerpinB9 
                 Human 
                 54, 55 
                 Inhibits cytotoxic granule 
                 2,000 mg to 5 ng; 
               
               
                   
                   
                   
                 proteases such as granzyme B 
                 1000 mM to 10 pM 
               
               
                 Serping1 
                 Human 
                 56-59 
                 C1 esterase inhibitor 
                 1,000 mg to 0.5 ng; 
               
               
                   
                   
                   
                   
                 500 mM to 10 pM 
               
               
                 Serpini1 
                 Human 
                 60-63 
                 Inhibits tPA, uPA and plasmin, 
                 2,000 mg to 5 ng; 
               
               
                 (neuroserpin) 
                   
                   
                 mutated in dementia 
                 1000 mM to 10 pM 
               
               
                   
               
            
           
         
       
     
     Formulations 
     The invention provides that any of the serpin compositions disclosed herein are formulated into a pharmaceutical composition. In some embodiments, a serpin and an anti-inflammatory therapeutic compound are the only active ingredients. In other embodiments, they are formulated with one or more additional active ingredients. In preferred embodiments, the combinatorial pharmaceutical compositions comprise steroids such as prednisolone or prednisone, anti-inflammatory compounds such as doxycycline, tetracycline, intravenous immunoglobulin, non-steroidal anti-inflammatory drugs (NSAID) such as celecoxib, indomethacin, naproxen, ibuprofen, acetaminophen, and rofecoxib. 
     The invention provides pharmaceutical compositions formulated with pharmaceutically acceptable excipients, carriers, diluents or vehicles. In some embodiments, they are formulated in powders, liquids, gels, pastes, suspensions, emulsions, or gaseous forms. In other embodiments, they are formulated into pharmaceutically acceptable dosage forms such as: tablets, capsules, caplets, powders, granules, ointments, crémes, solutions, suspensions, emulsions, suppositories, injections, inhalants, gels, particles, or aerosols. In other embodiments, the formulations are administered as disclosed herein. In other embodiments, serpins are administered in a free form, as pharmaceutically acceptable salts, in a time-release formulation, sequentially in a discrete manner, or in combination with other pharmaceutically active compounds. 
     In some embodiments, the serpins of the invention are delivered to a patient by intrathecal, intramuscular, intravascular, subcutaneous, intracranial, or intraocular injection. In a preferred embodiment, the serpin is A1AT. In another preferred embodiment, the serpins are provided in liquid and powder formulations at amounts ranging from about 1,000 mg/kg to about 50 ng/kg per dose, depending on the method of administration, potency and use. Some formulations may comprise recombinant serpins from about 1,000 mg to about 50 mg per dose. Some formulations may comprise recombinant serpins from about 75 mg to about 5 mg per dose. Some formulations may comprise recombinant serpins from about 5 mg to about 100 μg per dose. Other formulations may comprise recombinant serpins from about 150 μg to about 8 μg per dose. Yet other formulations comprise recombinant serpins from about 7.5 μg to about 50 ng per dose. In preferred embodiments, the formulated serpin is A1AT. 
     In other embodiments, the periodicity of dosing varies based on patient needs. In preferred embodiments, the dosing schedule is approximately: multiple times per day, daily, multiple times per week, weekly, bi-weekly, monthly, every 6 weeks, every two months, every three months, every four months, every five months, every 6 months, annually, or on an as-needed basis. In a preferred embodiment, the serpin is A1AT. In a more preferred embodiment 60 mg/kg is administered weekly 
     In other embodiments, the serpin is a human A1AT that is, for example, Prolastin-C (Grifols USA, Los Angeles, Calif.), Aralast NP (Baxter Healthcare Corp., Westlake Village, Calif.), Glassia (Baxter Healthcare Corp., Westlake Village, Calif.) and Zemaira (CSL Behring, King of Prussia, Pa.). In other embodiments, A1AT formulations derived from human blood comprise liquid and powder formulations at amounts ranging from about 1,000 mg/kg to about 50 ng/kg per dose, depending on the method of administration, potency and use. In other embodiments, the formulations comprise Recombinant A1AT from about 1,000 mg to about 50 mg per dose. In other embodiments, formulations comprise recombinant A1AT from about 75 mg to about 5 mg per dose. In other embodiments, formulations comprise Recombinant A1AT from about 5 mg to about 100 μg per dose. In other embodiments, formulations comprise recombinant A1AT from about 150 μg to about 8 μg per dose. In other embodiments, formulations comprise Recombinant A1AT from about 7.5 μg to about 50 ng per dose. 
     Exemplary drug formulations of the invention include aqueous solutions, organic solutions, powder formulations, solid formulations and mixed phase formulations. 
     Pharmaceutical compositions of this invention comprise any of the compounds of the present invention, and pharmaceutically acceptable salts thereof, with any pharmaceutically acceptable carrier, adjuvant or vehicle. Pharmaceutically acceptable carriers, adjuvants and vehicles that may be used in the pharmaceutical compositions of this invention include, but are not limited to, ion exchangers, alumina, aluminum stearate, lecithin, serum proteins, such as human serum albumin, buffer substances such as phosphates, glycine, sorbic acid, potassium sorbate, partial glyceride mixtures of saturated vegetable fatty acids, water, salts or electrolytes, such as protamine sulfate, disodium hydrogen phosphate, potassium hydrogen phosphate, sodium chloride, zinc salts, colloidal silica, magnesium trisilicate, polyvinyl pyrrolidone, cellulose-based substances, polyethylene glycol, sodium carboxymethylcellulose, polyacrylates, waxes, polyethylene-polyoxypropylene-block polymers, polyethylene glycol and wool fat. 
     Pharmaceutically acceptable salts retain the desired biological activity of the therapeutic composition without toxic side effects. Examples of such salts are (a) acid addition salts formed with inorganic acids, for example, hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid, nitric acid and the like/and salts formed with organic acids such as, for example, acetic acid, trifluoroacetic acid, tartaric acid, succinic acid, maleic acid, fumaric acid, gluconic acid, citric acid, malic acid, ascorbic acid, benzoic acid, tanic acid, pamoic acid, alginic acid, polyglutamic acid, naphthalenesulfonic acid, naphthalene disulfonic acid, polygalacturonic acid and the like; (b) base addition salts or complexes formed with polyvalent metal cations such as zinc, calcium, bismuth, barium, magnesium, aluminum, copper, cobalt, nickel, cadmium, and the like; or with an organic cation formed from N,N′-dibenzylethylenediamine or ethlenediamine; or (c) combinations of (a) and (b), e.g. a zinc tannate salt and the like. 
     The pharmaceutical compositions of this invention may be administered by subcutaneous, transdermal, oral, parenteral, inhalation, ocular, topical, rectal, nasal, buccal (including sublingual), vaginal, or implanted reservoir modes. The pharmaceutical compositions of this invention may contain any conventional, non-toxic, pharmaceutically-acceptable carriers, adjuvants or vehicles. The term parenteral as used herein includes subcutaneous, intracutaneous, intravenous, intramuscular, intraarticular, intrasynovial, intrastemal, intrathecal, intralesional, and intracranial injection or infusion techniques. 
     Also contemplated, in some embodiments, are pharmaceutical compositions comprising as an active ingredient, therapeutic compounds described herein, or pharmaceutically acceptable salt thereof, in a mixture with a pharmaceutically acceptable, non-toxic component. As mentioned above, such compositions may be prepared for parenteral administration, particularly in the form of liquid solutions or suspensions; for oral or buccal administration, particularly in the form of tablets or capsules; for intranasal administration, particularly in the form of powders, nasal drops, evaporating solutions or aerosols; for inhalation, particularly in the form of liquid solutions or dry powders with excipients, defined broadly; for transdermal administration, particularly in the form of a skin patch or microneedle patch; and for rectal or vaginal administration, particularly in the form of a suppository. 
     The compositions may conveniently be administered in unit dosage form and may be prepared by any of the methods well-known in the pharmaceutical art, for example, as described in Remington&#39;s Pharmaceutical Sciences, 17th ed., Mack Publishing Co., Easton, Pa. (1985), incorporated herein by reference in its entirety. Formulations for parenteral administration may contain as excipients sterile water or saline alkylene glycols such as propylene glycol, polyalkylene glycols such as polyethylene glycol, saccharides, oils of vegetable origin, hydrogenated napthalenes, serum albumin or other nanoparticles (as used in Abraxane™, American Pharmaceutical Partners, Inc. Schaumburg, Ill.), and the like. For oral administration, the formulation can be enhanced by the addition of bile salts or acylcarnitines. Formulations for nasal administration may be solid or solutions in evaporating solvents such as hydrofluorocarbons, and may contain excipients for stabilization, for example, saccharides, surfactants, submicron anhydrous alpha-lactose or dextran, or may be aqueous or oily solutions for use in the form of nasal drops or metered spray. For buccal administration, typical excipients include sugars, calcium stearate, magnesium stearate, pregelatinated starch, and the like. 
     Delivery of modified therapeutic compounds described herein to a subject over prolonged periods of time, for example, for periods of one week to one year, may be accomplished by a single administration of a controlled release system containing sufficient active ingredient for the desired release period. Various controlled release systems, such as monolithic or reservoir-type microcapsules, depot implants, polymeric hydrogels, osmotic pumps, vesicles, micelles, liposomes, transdermal patches, iontophoretic devices and alternative injectable dosage forms may be utilized for this purpose. Localization at the site to which delivery of the active ingredient is desired is an additional feature of some controlled release devices, which may prove beneficial in the treatment of certain disorders. 
     In certain embodiments for transdermal administration, delivery across the barrier of the skin would be enhanced using electrodes (e.g. iontophoresis), electroporation, or the application of short, high-voltage electrical pulses to the skin, radiofrequencies, ultrasound (e.g. sonophoresis), microprojections (e.g. microneedles), jet injectors, thermal ablation, magnetophoresis, lasers, velocity, or photomechanical waves. The drug can be included in single-layer drug-in-adhesive, multi-layer drug-in-adhesive, reservoir, matrix, or vapor style patches, or could utilize patchless technology. Delivery across the barrier of the skin could also be enhanced using encapsulation, a skin lipid fluidizer, or a hollow or solid microstructured transdermal system (MTS, such as that manufactured by 3M), jet injectors. Additives to the formulation to aid in the passage of therapeutic compounds through the skin include prodrugs, chemicals, surfactants, cell penetrating peptides, permeation enhancers, encapsulation technologies, enzymes, enzyme inhibitors, gels, nanoparticles and peptide or protein chaperones. 
     One form of controlled-release formulation contains the therapeutic compound or its salt dispersed or encapsulated in a slowly degrading, non-toxic, non-antigenic polymer such as copoly(lactic/glycolic) acid, as described in the pioneering work of Kent et al., U.S. Pat. No. 4,675,189, incorporated by reference herein. The compounds, or their salts, may also be formulated in cholesterol or other lipid matrix pellets, or silastomer matrix implants. Additional slow release, depot implant or injectable formulations will be apparent to the skilled artisan. See, for example, Sustained and Controlled Release Drug Delivery Systems, JR Robinson ed., Marcel Dekker Inc., New York, 1978; and Controlled Release of Biologically Active Agents, R W Baker, John Wiley &amp; Sons, New York, 1987. The foregoing are incorporated by reference in their entirety. 
     An additional form of controlled-release formulation comprises a solution of biodegradable polymer, such as copoly(lactic/glycolic acid) or block copolymers of lactic acid and PEG, is a bioacceptable solvent, which is injected subcutaneously or intramuscularly to achieve a depot formulation. Mixing of the therapeutic compounds described herein with such a polymeric formulation is suitable to achieve very long duration of action formulations. 
     When formulated for nasal administration, the absorption across the nasal mucous membrane may be further enhanced by surfactants, such as, for example, glycocholic acid, cholic acid, taurocholic acid, ethocholic acid, deoxycholic acid, chenodeoxycholic acid, dehdryocholic acid, glycodeoxycholic acid, cycledextrins and the like in an amount in the range of between about 0.1 and 15 weight percent, between about 0.5 and 4 weight percent, or about 2 weight percent. An additional class of absorption enhancers reported to exhibit greater efficacy with decreased irritation is the class of alkyl maltosides, such as tetradecylmaltoside (Arnold, J J et al., 2004, J Pharm Sci 93: 2205-13; Ahsan, F et al., 2001, Pharm Res 18:1742-46) and references therein, all of which are hereby incorporated by reference. 
     The pharmaceutical compositions may be in the form of a sterile injectable preparation, for example, as a sterile injectable aqueous or oleaginous suspension. This suspension may be formulated according to techniques known in the art using suitable dispersing or wetting agents (such as, for example, Tween 80) and suspending agents. The sterile injectable preparation may also be a sterile injectable solution or suspension in a non-toxic parenterally-acceptable diluent or solvent, for example, as a solution in 1,3-butanediol. Among the acceptable vehicles and solvents that may be employed are mannitol, water, Ringer&#39;s solution and isotonic sodium chloride solution. In addition, sterile, fixed oils are conventionally employed as a solvent or suspending medium. For this purpose, any bland fixed oil may be employed including synthetic mono- or diglycerides. Fatty acids, such as oleic acid and its glyceride derivatives are useful in the preparation of injectables, as are natural pharmaceutically-acceptable oils, such as olive oil or castor oil, especially in their polyoxyethylated versions. These oil solutions or suspensions may also contain a long-chain alcohol diluent or dispersant such as Ph. Helv or a similar alcohol. 
     The pharmaceutical compositions of this invention may be orally administered in any orally acceptable dosage form including, but not limited to, capsules, tablets, and aqueous suspensions and solutions. In the case of tablets for oral use, carriers that are commonly used include lactose and corn starch. Lubricating agents, such as magnesium stearate, are also typically added. For oral administration in a capsule form, useful diluents include lactose and dried corn starch. When aqueous suspensions are administered orally, the active ingredient is combined with emulsifying and suspending agents. If desired, certain sweetening and/or flavoring and/or coloring agents may be added. 
     The pharmaceutical compositions of this invention may also be administered in the form of suppositories for rectal administration. These compositions can be prepared by mixing a compound of this invention with a suitable non-irritating excipient that is solid at room temperature but liquid at the rectal temperature and therefore will melt in the rectum to release the active components. Such materials include, but are not limited to, cocoa butter, beeswax and polyethylene glycols. 
     Topical administration of the pharmaceutical compositions of this invention is especially useful when the desired treatment involves areas or organs readily accessible by topical application. For application topically to the skin, the pharmaceutical composition should be formulated with a suitable ointment containing the active components suspended or dissolved in a carrier. Carriers for topical administration of the compounds of this invention include, but are not limited to, mineral oil, liquid petroleum, white petroleum, propylene glycol, polyoxyethylene polyoxypropylene compound, emulsifying wax and water. Alternatively, the pharmaceutical composition can be formulated with a suitable lotion or cream containing the active compound suspended or dissolved in a carrier. Suitable carriers include, but are not limited to, mineral oil, sorbitan monostearate, polysorbate 60, cetyl esters wax, cetearyl alcohol, 2-octyldodecanol, benzyl alcohol and water. The pharmaceutical compositions of this invention may also be topically applied to the lower intestinal tract by rectal suppository formulation or in a suitable enema formulation. Topical transdermal patches are also included in this invention. 
     The pharmaceutical compositions of this invention may be administered by nasal aerosol or inhalation. Such compositions are prepared according to techniques well-known in the art of pharmaceutical formulation and may be prepared as solutions in saline, employing benzyl alcohol or other suitable preservatives, absorption promoters to enhance bioavailability, fluorocarbons, and/or other solubilizing or dispersing agents known in the art. 
     When formulated for delivery by inhalation, a number of formulations offer advantages. Adsorption of the therapeutic compound to readily dispersed solids such as diketopiperazines (for example, Technosphere particles (Pfutzner, A and Forst, T, 2005, Expert Opin Drug Deliv 2:1097-1106) or similar structures gives a formulation that results in rapid initial uptake of the therapeutic compound. Lyophilized powders, especially glassy particles, containing the therapeutic compound and an excipient are useful for delivery to the lung with good bioavailability, for example, see Exubera® (inhaled insulin, Pfizer, Inc. and Aventis Pharmaceuticals Inc.) and Afrezza® (inhaled insulin, Mannkind, Corp.). 
     Dosage levels of between about 0.01 and about 100 mg/kg body weight per day, preferably 0.5 and about 50 mg/kg body weight per day of the active ingredient compound are useful in the prevention and treatment of disease. Such administration can be used as a chronic or acute therapy. The amount of drug that may be combined with the carrier to produce a single dosage form will vary depending upon the host treated and the particular mode of administration. A typical preparation will contain from about 5% to about 95% active compound (w/w). Preferably, such preparations contain from about 20% to about 80% active compound. 
     Upon improvement of a patient&#39;s condition, a maintenance dose of a compound, composition or combination of this invention may be administered, if necessary. Subsequently, the dosage or frequency of administration, or both, may be reduced, as a function of the symptoms, to a level at which the improved condition is retained when the symptoms have been alleviated to the desired level, treatment should cease. Patients may, however, require intermittent treatment on a long-term basis upon any recurrence of disease symptoms. 
     As the skilled artisan will appreciate, lower or higher doses than those recited above may be required. Specific dosage and treatment regimens for any particular patient will depend upon a variety of factors, including the activity of the specific compound employed, the age, body weight, general health status, gender, diet, time of administration, rate of excretion, drug combination, the severity and course of an infection, the patient&#39;s disposition to the infection and the judgment of the treating physician. 
     The carrier-drug conjugates described herein provide advantages to drug manufacturers and patients over unmodified drugs. Specifically, the carrier-drug conjugate or formulation will be a more potent, longer lasting, and require smaller and less frequent dosing. This translates into lowered healthcare costs and more convenient drug administration schedules for patients. The carrier-drug conjugates can also provide subcutaneous or transdermal routes of administration as alternatives to intravenous injection. These routes can be self-administered by patients and thus improve patient compliance. 
     In order that the invention described herein may be more fully understood, the following examples are set forth. It should be understood that these examples are for illustrative purposes only and are not to be construed as limiting this invention in any manner. 
     Example 1—A1AT Reduces NMO Disease in a Mouse Model 
     C57BL/6 donor mice were immunized via subcutaneous injection with MOG-35-55 peptide in complete Freund&#39;s Adjuvant. This induces Experimental Autoimmune Encephalomyelitis (EAE), an animal model for progressive multiple sclerosis. (Miller et al., Curr. Protoc. Immunol., Chapter Unit 15.1 (2007); incorporated herein by reference in its entirety). The mice were boosted twice via intraperitoneal injection with Pertussis toxin on day 0, 2, and 7 days post-immunization. Mice were sacrificed and spleens and lymph nodes collected and resuspended into single cell suspensions. Cells were cultured with MOG peptide and IL-23 to increase Th17 skewing and cultured for 3 days. Cells were harvested and approximately 15×10̂6 cells were adoptively transferred into recipient C57BL/6 mice via intraperitoneal injection. Starting day 5 for 2 weeks until day 18, mice were administered daily via intraperitoneal injection with 100 uL of PBS or A1AT (2 mg A1AT formulated in PBS). Clinical scores were measured each day at approximately the same time of day. Clinical scores measure ascending paralysis. A score of 1 is a limp tail. A score of 2 includes hind limb weakness. A score of 3 includes hind limb paralysis. A score of 4 includes forelimb weakness. A score of 5 is indicated by death. (See Miller et al.). A1AT showed a significant improvement when compared to PBS treatment. n=10 mice per group. 
     Example 2—A1AT Reduces NMO Disease in a Mouse Model 
     Blood-derived human A1AT was compared to Sivelestat in a murine model of NMO. A less severe disease was induced when 12×10 6  Th17-polarized cells were adoptively transferred i.p. into recipient C57BL/6 mice. To induce Th17-polarized cells, C57BL/6 mice were induced with MOG 35-55 /CFA. 11 days later, their spleen cells were harvested and restimulated in culture with MOG 35-55  peptide (Miller et al., supra) for 3 days. 
     Mice received PBS, Sivelestat (0.5 mg), or A1AT (2 mg) as daily doses administered i.p. starting on Day 5 post-transfer until Day 18 post-transfer. There were 10 recipient mice per cohort. Error bars represent SEM. Points where A1AT compared to PBS and mean disease scores were significant (p&lt;0.05) are indicated (*). A1AT treatment reduced the NMO disease score compared to PBS (control) and was superior to Sivelestat at all days of overt signs of disease as well as delay onset of disease (see  FIG. 2 ). 
     Example 3—A1AT+Methylprednisolone Reduces NMO Disease in a Mouse Model 
     A more severe disease was induced by adoptively transferring a higher number of pathogenic Th17-polarized cells in order to demonstrate the additional efficacy from a combination treatment of A1AT plus methylprednisolone (Mpred) compared to individual treatments using a blinded study. 
     25×10 6  cells prepared as above were adoptively transferred i.p. into recipient C57BL/6 mice. Mice received PBS, Mpred (0.5 mg), AAT (2 mg), or both AAT+Mpred as daily doses administered i.p. starting on Day 4 post-transfer until Day 16 post-transfer. Ten recipient mice per cohort. Table 2 shows the Mean day of disease onset+/−SEM and p-value determined by the two-tailed Student&#39;s t-test; the end disease score at Day 17 post-transfer+/−SD, p-value determined by Mann-Whitney U test; and the mean maximum disease score (MMS)+/−SD, p-value by Mann-Whitney U test. The bold p-values indicate significant (p&lt;0.05) differences between the treatments when compared to PBS (control). 
     The AAT+Mpred combination demonstrated superior and significant delay of disease onset, showed improved disease end scores equivalent to Mpred alone, and improved mean maximum disease score (MMS) equivalent to Mpred alone. 
     
       
         
           
               
               
               
               
               
               
               
             
               
                 TABLE 2 
               
               
                   
               
               
                   
                 Mean Day of 
                   
                   
                   
                   
                   
               
               
                 Treatment 
                 Onset +/− SEM 
                 p-value 
                 End Score 
                 p-value 
                 MMS +/− SD 
                 p-value 
               
               
                   
               
             
            
               
                 PBS 
                 7.9 +/− 0.3 
                   
                 3.00 +/− 1.11 
                   
                 3.15 +/− 1.11 
                   
               
               
                 Mpred 
                 8.5 +/− 0.4 
                 0.2520 
                 2.25 +/− 0.42 
                 
                   0.0039 
                 
                 2.95 +/− 0.44 
                 
                   0.0228 
                 
               
               
                 A1AT 
                 8.4 +/− 0.4 
                 0.3110 
                 3.10 +/− 0.57 
                 0.6890 
                 3.50 +/− 0.00 
                 0.3173 
               
               
                 A1AT + Mpred 
                 9.3 +/− 0.5 
                 
                   0.0164 
                 
                 2.15 +/− 1.00 
                 
                   0.0150 
                 
                 2.70 +/− 1.06 
                 
                   0.0447 
                 
               
               
                   
               
            
           
         
       
     
     Mean disease scores showed that A1AT+Mpred treatment reduced the disease over all days measured more than either treatment alone (see  FIG. 3 ). AAT alone showed early efficacy compared to Mpred alone and PBS (control) on Day 5 and 6 but afterwards did not show therapeutic effect. While not being bound to theory, this may be due to anti-drug immunogenicity of the human AAT in mouse that is known to develop (70) that may not have developed in our previous less severe disease induction, and where the Mpred in combination with AAT treatment may have diminished the anti-drug immunogenicity effect. 
     Histological analysis showed that A1AT+Mpred and A1AT alone reduced the number of inflammatory foci compared to Mpred alone. Additionally, A1AT+Mpred similarly reduced demyelination and the number of apoptotic cells when compared to Mpred alone. 
     
       
         
           
               
               
               
               
               
               
               
             
               
                 TABLE 3 
               
               
                   
               
               
                   
                 Inflammatory 
                   
                 Demyelination 
                   
                 Apoptotic 
                   
               
               
                 Treatment 
                 foci +/− SD 
                 p-value 
                 (H + E) 
                 p-value 
                 Cells +/− SD 
                 p-value 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
               
               
               
            
               
                 PBS 
                 3.6 +/− 0.5 
                   
                 1.8 +/− 0.2 
                   
                 2.9 +/− 0.9 
                   
               
               
                 Mpred 
                 3.0 +/− 0.9 
                 0.2856 
                 1.2 +/− 0.3 
                 
                   0.0325 
                 
                 1.3 +/− 0.9 
                 
                   0.0393 
                 
               
               
                 A1AT 
                 2.0 +/− 0.5 
                 
                   0.0037 
                 
                 1.8 +/− 0.4 
                 1.000 
                 2.5 +/− 0.3 
                 0.4262 
               
               
                 A1AT + Mpred 
                 2.5 +/− 0.6 
                 
                   0.0369 
                 
                 1.3 +/− 0.3 
                 
                   0.0360 
                 
                 1.5 +/− 0.3 
                 
                   0.0273 
                 
               
               
                   
               
            
           
         
       
     
     Table 3 shows histopathology scores in a blinded study. An NMO mouse model as described above was used. Spines were collected from 4 mice per treatment cohort on Day 18 and prepared for histology. Sections from cervical, thoracic and lumbar spine regions were scored and averaged. Table 3 shows the number of inflammatory foci per section &gt;20 cells+/−SD, p-value by two-tailed Student&#39;s t-test; demyelination scoring of hematoxylin and eosin stained section+/−SD, p-value by Mann-Whitney U test; and apoptotic cell counts+/−SD, p-value by two-tailed Student&#39;s t-test. Bold formatting indicates significant (p&lt;0.05) difference of treatment compared to PBS (control). 
     Body weight loss results from, and is a prognostic measurement of, autoimmune diseases such as NMO. A1AT+Mpred resulted in less body weight loss than either treatment alone (see  FIG. 4 ). Ten recipient mice per cohort were used in this blinded study. The graph shows mean body weight as a percentage of the value measured at day 0+/−SEM. Interestingly, Mpred treatment alone appeared to cause early weight loss from Day 5 to Day 7. While not being bound to theory, this suggests the possibility that weight loss is a side effect of the steroid rather than NMO disease. At later times, the Mpred cohort weight loss was similar to PBS (control) even though Mpred had a lower disease score. Thus, Mpred toxicity side effects may be ameliorated by the AAT+Mpred combination cohort. 
     Example 4—A1AT+Methylprednisolone Reduces Autoimmune Cytokine Profile 
     Ex vivo cytokine measurements from spleen cells of Th17-polarized cell transplanted mice restimulated with MOG peptide were conducted to survey effector and memory recall responses of the immune cell compartment, primarily from T cells. Spleens were collected from 6 mice per treatment cohort on Day 18. Single cell suspensions were prepared and cultured with the indicated amounts of MOG35-55 peptide. Supernatants were collected after 3 days of culture and IL-17A, IFN-γ, IL-6, or IL-2 measured by cytokine bead assay (BD Biosciences, San Jose, Calif., Cat. No. 560485). The results in this blinded study were expressed in cytokine pg/mL+/−SEM. 
     Consistent with the mouse NMO model, A1AT alone and A1AT+Mpred decreased the inflammatory cytokines IL-17A compared to PBS and Mpred alone ( FIG. 5A ), and decreased IFN-γ when compared to Mpred alone ( FIG. 5B ). All treatments resulted in increased IL-6 compared to PBS ( FIG. 5C ). IL-2 levels were higher without antigenic restimulation (0 MOG peptide) when treated with A1AT alone or A1AT+Mpred when compared to Mpred alone ( FIG. 5D ). IL-2 promotes T cell proliferation but is also a key cytokine for the maintenance of regulatory T cells in vivo. TNF-α levels were similar and IL-4 levels were at the borderline limit of detection in all four cohorts (data not shown). These cytokine restimulation measurements show that AAT and Mpred treatments resulted in differential immunomodulation of NMO disease that helps explain their additional therapeutic efficacy when used in combination. 
     Exemplary Sequences 
     
       
         
           
               
               
            
               
                 Sequence ID No. 1 
                   
               
               
                 AlAT (Human) Protein 
                   
               
               
                 MPSSVSWGIL LLAGLCCLVP VSLAEDPQGD AAQKTDTSHH DQDHPTFNKI 
               
               
                   
               
               
                 TPNLAEFAFS LYRQLAHQSN STNIFFSPVS IATAFAMLSL GTKADTHDEI 
               
               
                   
               
               
                 LEGLNFNLTE IPEAQIHEGF QELLRTLNQP DSQLQLTTGN GLFLSEGLKL 
               
               
                   
               
               
                 VDKFLEDVKK LYHSEAFTVN FGDTEEAKKQ INDYVEKGTQ GKIVDLVKEL 
               
               
                   
               
               
                 DRDTVFALVN YIFFKGKWER PFEVKDTEEE DFHVDQVTTV KVPMMKRLGM 
               
               
                   
               
               
                 FNIQHCKKLS SWVLLMKYLG NATAIFFLPD EGKLQHLENE LTHDIITKFL 
               
               
                   
               
               
                 ENEDRRSASL HLPKLSITGT YDLKSVLGQL GITKVFSNGA DLSGVTEEAP 
               
               
                   
               
               
                 LKLSKAVHKA VLTIDEKGTE AAGAMFLEAI PMSIPPEVKF NKPFVFLMIE 
               
               
                   
               
               
                 QNTKSPLFMG KVVNPTQK 
               
               
                   
               
               
                 SEQ ID No. 2 
                   
               
               
                 AlAT (Human) cDNA 
                   
               
               
                 ATGCCGTCTTCTGTCTCGTGGGGCATCCTCCTGCTGGCAGGCCTGTGCTGCCT 
               
               
                   
               
               
                 GGTCCCTGTCTCCCTGGCTGAGGATCCCCAGGGAGATGCTGCCCAGAAGACA 
               
               
                   
               
               
                 GATACATCCCACCATGATCAGGATCACCCAACCTTCAACAAGATCACCCCCA 
               
               
                   
               
               
                 ACCTGGCTGAGTTCGCCTTCAGCCTATACCGCCAGCTGGCACACCAGTCCAAC 
               
               
                   
               
               
                 AGCACCAATATCTTCTTCTCCCCAGTGAGCATCGCTACAGCCTTTGCAATGCT 
               
               
                   
               
               
                 CTCCCTGGGGACCAAGGCTGACACTCACGATGAAATCCTGGAGGGCCTGAAT 
               
               
                   
               
               
                 TTCAACCTCACGGAGATTCCGGAGGCTCAGATCCATGAAGGCTTCCAGGAAC 
               
               
                   
               
               
                 TCCTCCGTACCCTCAACCAGCCAGACAGCCAGCTCCAGCTGACCACCGGCAA 
               
               
                   
               
               
                 TGGCCTGTTCCTCAGCGAGGGCCTGAAGCTAGTGGATAAGTTTTTGGAGGATG 
               
               
                   
               
               
                 TTAAAAAGTTGTACCACTCAGAAGCCTTCACTGTCAACTTCGGGGACACCGA 
               
               
                   
               
               
                 AGAGGCCAAGAAACAGATCAACGATTACGTGGAGAAGGGTACTCAAGGGAA 
               
               
                   
               
               
                 AATTGTGGATTTGGTCAAGGAGCTTGACAGAGACACAGTTTTTGCTCTGGTGA 
               
               
                   
               
               
                 ATTACATCTTCTTTAAAGGCAAATGGGAGAGACCCTTTGAAGTCAAGGACAC 
               
               
                   
               
               
                 CGAGGAAGAGGACTTCCACGTGGACCAGGTGACCACCGTGAAGGTGCCTATG 
               
               
                   
               
               
                 ATGAAGCGTTTAGGCATGTTTAACATCCAGCACTGTAAGAAGCTGTCCAGCTG 
               
               
                   
               
               
                 GGTGCTGCTGATGAAATACCTGGGCAATGCCACCGCCATCTTCTTCCTGCCTG 
               
               
                   
               
               
                 ATGAGGGGAAACTACAGCACCTGGAAAATGAACTCACCCACGATATCATCAC 
               
               
                   
               
               
                 CAAGTTCCTGGAAAATGAAGACAGAAGGTCTGCCAGCTTACATTTACCCAAA 
               
               
                   
               
               
                 CTGTCCATTACTGGAACCTATGATCTGAAGAGCGTCCTGGGTCAACTGGGCAT 
               
               
                   
               
               
                 CACTAAGGTCTTCAGCAATGGGGCTGACCTCTCCGGGGTCACAGAGGAGGCA 
               
               
                   
               
               
                 CCCCTGAAGCTCTCCAAGGCCGTGCATAAGGCTGTGCTGACCATCGACGAGA 
               
               
                   
               
               
                 AAGGGACTGAAGCTGCTGGGGCCATGTTTTTAGAGGCCATACCCATGTCTATC 
               
               
                   
               
               
                 CCCCCCGAGGTCAAGTTCAACAAACCCTTTGTCTTCTTAATGATTGAACAAAA 
               
               
                   
               
               
                 TACCAAGTCTCCCCTCTTCATGGGAAAAGTGGTGAATCCCACCCAAAAATAA 
               
               
                   
               
               
                 SEQ ID No. 3 
                   
               
               
                 CrmA (Cowpox virus) Protein 
                   
               
               
                 MDIFREIASSMKGENVFISPPSISSVLTILYYGANGSTAEQLSKYVEKEADKNKDDI 
               
               
                   
               
               
                 SFKSMNKVYGRYSAVFKDSFLRKIGDNFQTVDFTDCRTVDAINKCVDIFTEGKIN 
               
               
                   
               
               
                 PLLDEPLSPDTCLLAISAVYFKAKWLMPFEKEFTSDYPFYVSPTEMVDVSMMSM 
               
               
                   
               
               
                 YGEAFNHASVKESFGNFSIIELPYVGDTSMVVILPDNIDGLESIEQNLTDTNFKKW 
               
               
                   
               
               
                 CDSMDAMFIDVHIPKFKVTGSYNLVDALVKLGLTEVFGSTGDYSNMCNSDVSVD 
               
               
                   
               
               
                 AMIHKTYIDVNEEYTEAAAATCALVADCASTVTNEFCADHPFIYVIRHVDGKILF 
               
               
                   
               
               
                 VGRYCSPTTN 
               
               
                   
               
               
                 SEQ ID No. 4 
                   
               
               
                 CrmA (Cowpox virus) cDNA 
                   
               
               
                 ATGGATATCTTCAGGG AAATCGCATC TTCTATGAAA GGAGAGAATG 
               
               
                   
               
               
                 TATTCATTTC TCCACCGTCAATCTCGTCAG TATTGACAAT ACTGTATTAT 
               
               
                   
               
               
                 GGAGCTAATG GATCCACTGC TGAACAGCTATCAAAATATG TAGAAAAGGA 
               
               
                   
               
               
                 GGCGGACAAG AATAAGGATG ATATCTCATT CAAGTCCATGAATAAAGTAT 
               
               
                   
               
               
                 ATGGGCGATA TTCTGCAGTG TTTAAAGATT CCTTTTTGAG AAAAATTGGA 
               
               
                   
               
               
                 GATAATTTCC AAACTGTTGA CTTCACTGAT TGTCGCACTG TAGATGCGAT 
               
               
                   
               
               
                 CAACAAGTGTGTTGATATCT TCACTGAGGG GAAAATTAAT CCACTATTGG 
               
               
                   
               
               
                 ATGAACCATT GTCTCCAGATACCTGTCTCC TAGCAATTAG TGCCGTATAC 
               
               
                   
               
               
                 TTTAAAGCAA AATGGTTGAT GCCATTTGAAAAGGAATTTA CCAGTGATTA 
               
               
                   
               
               
                 TCCCTTTTAC GTATCTCCAA CGGAAATGGT AGATGTAAGTATGATGTCTA 
               
               
                   
               
               
                 TGTACGGCGA GGCATTTAAT CACGCATCTG TAAAAGAATC ATTCGGCAAC 
               
               
                   
               
               
                 TTTTCAATCA TAGAACTGCC ATATGTTGGA GATACTAGTA TGGTGGTAAT 
               
               
                   
               
               
                 TCTTCCAGACAATATTGATG GACTAGAATC CATAGAACAA AATCTAACAG 
               
               
                   
               
               
                 ATACAAATTT TAAGAAATGGTGTGACTCTA TGGATGCTAT GTTTATCGAT 
               
               
                   
               
               
                 GTGCACATTC CCAAGTTTAA GGTAACAGGCTCGTATAATC TGGTGGATGC 
               
               
                   
               
               
                 GCTAGTAAAG TTGGGACTGA CAGAGGTGTT CGGTTCAACTGGAGATTATA 
               
               
                   
               
               
                 GCAATATGTG TAATTCAGAT GTGAGTGTCG ACGCTATGAT CCACAAAACG 
               
               
                   
               
               
                 TATATAGATG TCAATGAAGA GTATACAGAA GCAGCTGCAG CAACTTGTGC 
               
               
                   
               
               
                 GCTGGTGGCAGACTGTGCAT CAACAGTTAC AAATGAGTTC TGTGCAGATC 
               
               
                   
               
               
                 ATCCGTTCAT CTATGTGATTAGGCATGTCG ATGGCAAAAT TCTTTTCGTT 
               
               
                   
               
               
                 GGTAGATATT GCTCTCCAAC AACTAATTAA 
               
               
                   
               
               
                 SEQ ID No. 5 
                   
               
               
                 Serpin1 ( Arabidopsis ) Protein 
                   
               
               
                 MDVRESISLQ NQVSMNLAKH VITTVSQNSN VIFSPASINV VLSIIAAGSA 
               
               
                   
               
               
                 GATKDQILSFLKFSSTDQLN SFSSEIVSAV LADGSANGGP KLSVANGAWI 
               
               
                   
               
               
                 DKSLSFKPSF KQLLEDSYKAASNQADFQSK AVEVIAEVNS WAEKETNGLI 
               
               
                   
               
               
                 TEVLPEGSAD SMTKLIFANA LYFKGTWNEKFDESLTQEGE FHLLDGNKVT 
               
               
                   
               
               
                 APFMTSKKKQ YVSAYDGFKV LGLPYLQGQD KRQFSMYFYLPDANNGLSDL 
               
               
                   
               
               
                 LDKIVSTPGF LDNHIPRRQV KVREFKIPKF KFSFGFDASN VLKGLGLTSP 
               
               
                   
               
               
                 FSGEEGLTEM VESPEMGKNL CVSNIFHKAC IEVNEEGTEA AAASAGVIKL 
               
               
                   
               
               
                 RGLLMEEDEIDFVADHPFLL VVTENITGVV LFIGQVVDPL H 
               
               
                   
               
               
                 SEQ ID No. 6 
                   
               
               
                 Serpin1 ( Arabidopsis ) DNA 
                   
               
               
                 CGTCTTCTCC TAAACCCAGC AAATTCGTTT ACCAGTCATC ACCACCACAA 
               
               
                   
               
               
                 CCTCCGGCGA AAATGGACGT GCGTGAATCA ATCTCACTGC AAAACCAAGT 
               
               
                   
               
               
                 CTCCATGAAT CTCGCAAAAC ACGTAATCAC CACCGTCTCT CAAAACTCCA 
               
               
                   
               
               
                 ACGTCATCTT CTCACCGGCT TCAATCAACG TCGTACTCAG TATAATCGCC 
               
               
                   
               
               
                 GCTGGATCCG CCGGCGCTAC CAAAGATCAG ATCCTCTCGT TTCTCAAATT 
               
               
                   
               
               
                 CTCTTCCACT GATCAACTTA ATTCATTCTC TTCCGAAATC GTCTCCGCTG 
               
               
                   
               
               
                 TTCTCGCTGA CGGTAGTGCT AACGGTGGTC CTAAGCTCTC GGTGGCTAAT 
               
               
                   
               
               
                 GGCGCCTGGA TCGATAAGTC TCTCTCCTTT AAACCTTCCT TTAAACAGCT 
               
               
                   
               
               
                 CTTGGAAGAT TCGTATAAAG CTGCTTCGAA TCAAGCTGAT TTTCAATCGA 
               
               
                   
               
               
                 AGGCTGTGGA GGTGATTGCT GAAGTGAATT CATGGGCTGA AAAGGAGACA 
               
               
                   
               
               
                 AATGGTCTCA TCACTGAGGT TCTTCCAGAA GGATCAGCTG ATAGTATGAC 
               
               
                   
               
               
                 CAAACTGATA TTTGCAAATG CATTGTACTT CAAGGGAACA TGGAACGAGA 
               
               
                   
               
               
                 AATTCGATGA GTCGTTAACA CAAGAAGGCG AGTTTCACCT TCTTGACGGT 
               
               
                   
               
               
                 AACAAAGTGA CTGCACCATT CATGACCAGC AAGAAGAAAC AATACGTAAG 
               
               
                   
               
               
                 TGCTTACGAT GGTTTCAAAG TTTTGGGACT TCCTTACTTA CAAGGACAGG 
               
               
                   
               
               
                 ATAAGCGACA ATTCTCCATG TACTTTTATC TTCCCGATGC AAACAACGGA 
               
               
                   
               
               
                 CTGTCTGATC TTCTGGACAA AATAGTTTCC ACTCCTGGGT TCTTAGACAA 
               
               
                   
               
               
                 CCACATCCCA CGCAGACAAG TTAAAGTCCG CGAATTCAAG ATTCCAAAGT 
               
               
                   
               
               
                 TTAAATTCTC TTTCGGGTTC GATGCTTCAA ATGTTTTAAA AGGATTGGGA 
               
               
                   
               
               
                 CTGACTTCGC CTTTCAGCGG TGAAGAAGGT TTAACTGAGA TGGTTGAATC 
               
               
                   
               
               
                 TCCTGAGATG GGGAAGAATC TATGCGTATC GAACATTTTC CATAAAGCGT 
               
               
                   
               
               
                 GTATCGAAGT GAATGAAGAA GGAACAGAAG CTGCAGCTGC ATCAGCTGGA 
               
               
                   
               
               
                 GTTATAAAGC TAAGAGGATT GCTTATGGAG GAAGATGAAA TAGATTTTGT 
               
               
                   
               
               
                 TGCAGACCAT CCGTTTCTAT TGGTGGTCAC AGAGAACATA ACAGGAGTGG 
               
               
                   
               
               
                 TTCTGTTCAT TGGCCAAGTT GTTGATCCGT TGCATTAATC TAAAGCTAAT 
               
               
                   
               
               
                 GTGGAAGTTT TTGGTTTTAC TTAAAATAAA TGAGTCATTG GTTTTGAGGA 
               
               
                   
               
               
                 CTCATCTTTA TGTAACATCC TTTGTCTTGA CTCTTTGATG TGTGTAAGAA 
               
               
                   
               
               
                 TAATAGTGAT ACATAACAGC TTTTCTTCTG TATTTGGATC ACATGTACTG 
               
               
                   
               
               
                 AACTGATAGA CATACATACA TGTGATGCAT CTTAATGATT CACTGT 
               
               
                   
               
               
                 SEQ ID No. 7 
                   
               
               
                 SerpinB9 (Human) protein 
                   
               
               
                 METLSNASGTFAIRLLKILCQDNPSHNVFCSPVSISSALAMVLLGAKGNTATQMA 
               
               
                   
               
               
                 QALSLNTEEDIHRAFQSLLTEVNKAGTQYLLRTANRLFGEKTCQFLSTFKESCLQF 
               
               
                   
               
               
                 YHAELKELSFIRAAEESRKHINTWVSKKTEGKIEELLPGSSIDAETRLVLVNAIYFK 
               
               
                   
               
               
                 GKWNEPFDETYTREMPFKINQEEQRPVQMMYQEATFKLAHVGEVRAQLLELPY 
               
               
                   
               
               
                 ARKELSLLVLLPDDGVELSTVEKSLTFEKLTAWTKPDCMKSTEVEVLLPKFKLQE 
               
               
                   
               
               
                 DYDMESVLRHLGIVDAFQQGKADLSAMSAERDLCLSKFVHKSFVEVNEEGTEAA 
               
               
                   
               
               
                 AASSCFVVAECCMESGPRFCADHPFLFFIRHNRANSILFCGRFSSP 
               
               
                   
               
               
                 SEQ ID No. 8 
                   
               
               
                 SerpinB9 (Human) cDNA 
                   
               
               
                 ATGGAAACTC TTTCTAATGC AAGTGGTACT TTTGCCATAC GCCTTTTAAA 
               
               
                   
               
               
                 GATACTGTGTCAAGATAACC CTTCGCACAA CGTGTTCTGT TCTCCTGTGA 
               
               
                   
               
               
                 GCATCTCCTC TGCCCTGGCCATGGTTCTCC TAGGGGCAAA GGGAAACACC 
               
               
                   
               
               
                 GCAACCCAGA TGGCCCAGGC ACTGTCTTTAAACACAGAGG AAGACATTCA 
               
               
                   
               
               
                 TCGGGCTTTC CAGTCGCTTC TCACTGAAGT GAACAAGGCTGGCACACAGT 
               
               
                   
               
               
                 ACCTGCTGAG AACGGCCAAC AGGCTCTTTG GAGAGAAAAC TTGTCAGTTC 
               
               
                   
               
               
                 CTCTCAACGT TTAAGGAATC CTGTCTTCAA TTCTACCATG CTGAGCTGAA 
               
               
                   
               
               
                 GGAGCTTTCCTTTATCAGAG CTGCAGAAGA GTCCAGGAAA CACATCAACA 
               
               
                   
               
               
                 CCTGGGTCTC AAAAAAGACCGAAGGTAAAA TTGAAGAGTT GTTGCCGGGT 
               
               
                   
               
               
                 AGCTCAATTG ATGCAGAAAC CAGGCTGGTTCTTGTCAATG CCATCTACTT 
               
               
                   
               
               
                 CAAAGGAAAG TGGAATGAAC CGTTTGACGA AACATACACAAGGGAAATGC 
               
               
                   
               
               
                 CCTTTAAAAT AAACCAGGAG GAGCAAAGGC CAGTGCAGAT GATGTATCAG 
               
               
                   
               
               
                 GAGGCCACGT TTAAGCTCGC CCACGTGGGC GAGGTGCGCG CGCAGCTGCT 
               
               
                   
               
               
                 GGAGCTGCCCTACGCCAGGA AGGAGCTGAG CCTGCTGGTG CTGCTGCCTG 
               
               
                   
               
               
                 ACGACGGCGT GGAGCTCAGCAAGAGTACTG AGGTTGAAGT TCTCCTTCCA 
               
               
                   
               
               
                 AAATTTAAAC TACAAGAGGA TTATGACATGGAATCTGTGC TTCGGCATTT 
               
               
                   
               
               
                 GGGAATTGTT GATGCCTTCC AACAGGGCAA GGCTGACTTGTCGGCAATGT 
               
               
                   
               
               
                 CAGCGGAGAG AGACCTGTGT CTGTCCAAGT TCGTGCACAA GAGTTTTGTG 
               
               
                   
               
               
                 GAGGTGAATG AAGAAGGCAC CGAGGCAGCG GCAGCGTCGA GCTGCTTTGT 
               
               
                   
               
               
                 AGTTGCAGAGTGCTGCATGG AATCTGGCCC CAGGTTCTGT GCTGACCACC 
               
               
                   
               
               
                 CTTTCCTTTT CTTCATCAGGCACAACAGAG CCAACAGCAT TCTGTTCTGT 
               
               
                   
               
               
                 GGCAGGTTCT CATCGCCA 
               
               
                   
               
               
                 SEQ ID No. 9 
                   
               
               
                 SerpinA3 (Human) Protein 
                   
               
               
                 MERMLPLLTL GLLAAGFCPA VLCHPNSPLD EENLTQENQD RGTHVDLGLA 
               
               
                   
               
               
                 SANVDFAFSLYKQSPRWSIR LCLMYLRRAQ KHLLPQQSKS PSFLH 
               
               
                   
               
               
                 SEQ ID No. 10 
                   
               
               
                 SerpinA3 (Human) Protein Precursor 
                   
               
               
                 MERMLPLLALGLLAAGFCPAVLCHPNSPLDEENLTQENQDRGTHVDLGLASANV 
               
               
                   
               
               
                 DFAFSLYKQLVLKAPDKNVIFSPLSISTALAFLSLGAHNTTLTEILKGLKFNLTETS 
               
               
                   
               
               
                 EAEIHQSFQHLLRTLNQSSDELQLSMGNAMFVKEQLSLLDRFTEDAKRLYGSEAF 
               
               
                   
               
               
                 ATDFQDSAAAKKLINDYVKNGTRGKITDLIKDLDSQTMMVLVNYIFFKAKWEMP 
               
               
                   
               
               
                 FDPQDTHQSRFYLSKKKWVMVPMMSLHHLTIPYFRDEELSCTVVELKYTGNASA 
               
               
                   
               
               
                 LFILPDQDKMEEVEAMLLPETLKRWRDSLEFREIGELYLPKFSISRDYNLNDILLQ 
               
               
                   
               
               
                 LGIEEAFTSKADLSGITGARNLAVSQVVHKAVLDVFEEGTEASAATAVKITLLSA 
               
               
                   
               
               
                 LVETRTIVRFNRPFLMIIVPTDTQNIFFMSKVTNPKQA 
               
               
                   
               
               
                 SEQ ID No. 11 
                   
               
               
                 SerpinA3 (Human) cDNA precursor 
                   
               
               
                 ATGGAGAGAAT GTTACCTCTC CTGGCTCTGG GGCTCTTGGC GGCTGGGTTC 
               
               
                   
               
               
                 TGCCCTGCTG TCCTCTGCCA CCCTAACAGC CCACTTGACG AGGAGAATCT 
               
               
                   
               
               
                 GACCCAGGAG AACCAAGACC GAGGGACACA CGTGGACCTC GGATTAGCCT 
               
               
                   
               
               
                 CCGCCAACGT GGACTTCGCT TTCAGCCTGT ACAAGCAGTT AGTCCTGAAG 
               
               
                   
               
               
                 GCCCCTGATA AGAATGTCAT CTTCTCCCCA CTGAGCATCT CCACCGCCTT 
               
               
                   
               
               
                 GGCCTTCCTG TCTCTGGGGG CCCATAATAC CACCCTGACA GAGATTCTCA 
               
               
                   
               
               
                 AAGGCCTCAA GTTCAACCTC ACGGAGACTT CTGAGGCAGA AATTCACCAG 
               
               
                   
               
               
                 AGCTTCCAGC ACCTCCTGCG CACCCTCAAT CAGTCCAGCG ATGAGCTGCA 
               
               
                   
               
               
                 GCTGAGTATG GGAAATGCCA TGTTTGTCAA AGAGCAACTC AGTCTGCTGG 
               
               
                   
               
               
                 ACAGGTTCAC GGAGGATGCC AAGAGGCTGT ATGGCTCCGA GGCCTTTGCC 
               
               
                   
               
               
                 ACTGACTTTC AGGACTCAGC TGCAGCTAAG AAGCTCATCA ACGACTACGT 
               
               
                   
               
               
                 GAAGAATGGA ACTAGGGGGA AAATCACAGA TCTGATCAAG GACCTTGACT 
               
               
                   
               
               
                 CGCAGACAAT GATGGTCCTG GTGAATTACA TCTTCTTTAA AGCCAAATGG 
               
               
                   
               
               
                 GAGATGCCCT TTGACCCCCA AGATACTCAT CAGTCAAGGT TCTACTTGAG 
               
               
                   
               
               
                 CAAGAAAAAG TGGGTAATGG TGCCCATGAT GAGTTTGCAT CACCTGACTA 
               
               
                   
               
               
                 TACCTTACTT CCGGGACGAG GAGCTGTCCT GCACCGTGGT GGAGCTGAAG 
               
               
                   
               
               
                 TACACAGGCA ATGCCAGCGC ACTCTTCATC CTCCCTGATC AAGACAAGAT 
               
               
                   
               
               
                 GGAGGAAGTG GAAGCCATGC TGCTCCCAGA GACCCTGAAG CGGTGGAGAG 
               
               
                   
               
               
                 ACTCTCTGGA GTTCAGAGAG ATAGGTGAGC TCTACCTGCC AAAGTTTTCC 
               
               
                   
               
               
                 ATCTCGAGGG ACTATAACCT GAACGACATA CTTCTCCAGC TGGGCATTGA 
               
               
                   
               
               
                 GGAAGCCTTC ACCAGCAAGG CTGACCTGTC AGGGATCACA GGGGCCAGGA 
               
               
                   
               
               
                 ACCTAGCAGT CTCCCAGGTG GTCCATAAGG CTGTGCTTGA TGTATTTGAG 
               
               
                   
               
               
                 GAGGGCACAG AAGCATCTGC TGCCACAGCA GTCAAAATCA CCCTCCTTTC 
               
               
                   
               
               
                 TGCATTAGTG GAGACAAGGA CCATTGTGCG TTTCAACAGG CCCTTCCTGA 
               
               
                   
               
               
                 TGATCATTGT CCCTACAGAC ACCCAGAACA TCTTCTTCAT GAGCAAAGTC 
               
               
                   
               
               
                 ACCAATCCCA AGCAAGCCTA G 
               
               
                   
               
               
                 SEQ ID No. 12 
                   
               
               
                 SerpinA4 transcript variant 3 (Human) Protein 
                   
               
               
                 MHLIDYLLLLLVGLLALSHGQLHVEHDGESCSNSSHQQILETGEGSPSLKIAPANA 
               
               
                   
               
               
                 DFAFRFYYLIASETPGKNIFFSPLSISAAYAMLSLGACSHSRSQILEGLGFNLTELSE 
               
               
                   
               
               
                 SDVHRGFQHLLHTLNLPGHGLETRVGSALFLSHNLKFLAKFLNDTMAVYEAKLF 
               
               
                   
               
               
                 HTNFYDTVGTIQLINDHVKKETRGKIVDLVSELKKDVLMVLVNYIYFKALWEKP 
               
               
                   
               
               
                 FISSRTTPKDFYVDENTTVRVPMMLQDQEHHWYLHDRYLPCSVLRMDYKGDAT 
               
               
                   
               
               
                 VFFILPNQGKMREIEEVLTPEMLMRWNNLLRKRNFYKKLELHLPKFSISGSYVLD 
               
               
                   
               
               
                 QILPRLGFTDLFSKWADLSGITKQQKLEASKSFHKATLDVDEAGTEAAAATSFAI 
               
               
                   
               
               
                 KFFSAQTNRHILRFNRPFLVVIFSTSTQSVLFLGKVVDPTKP 
               
               
                   
               
               
                 SEQ ID No. 13 
                   
               
               
                 SerpinA4 transcript variant 3 (Human) cDNA 
                   
               
               
                 ATGCATCT TATCGACTAC CTGCTCCTCC TGCTGGTTGG ACTACTGGCC 
               
               
                   
               
               
                 CTTTCTCATG GCCAGCTGCA CGTTGAGCAT GATGGTGAGA GTTGCAGTAA 
               
               
                   
               
               
                 CAGCTCCCAC CAGCAGATTC TGGAGACAGG TGAGGGCTCC CCCAGCCTCA 
               
               
                   
               
               
                 AGATAGCCCC TGCCAATGCT GACTTTGCCT TCCGCTTCTA CTACCTGATC 
               
               
                   
               
               
                 GCTTCGGAGA CCCCGGGGAA GAACATCTTT TTCTCCCCGC TGAGCATCTC 
               
               
                   
               
               
                 GGCGGCCTAC GCCATGCTTT CCCTGGGGGC CTGCTCACAC AGCCGCAGCC 
               
               
                   
               
               
                 AGATCCTTGA GGGCCTGGGC TTCAACCTCA CCGAGCTGTC TGAGTCCGAT 
               
               
                   
               
               
                 GTCCATAGGG GCTTCCAGCA CCTCCTGCAC ACTCTCAACC TCCCCGGCCA 
               
               
                   
               
               
                 TGGGCTGGAA ACACGCGTGG GCAGTGCTCT GTTCCTGAGC CACAACCTGA 
               
               
                   
               
               
                 AGTTCCTTGC AAAATTCCTG AATGACACCA TGGCCGTCTA TGAGGCTAAA 
               
               
                   
               
               
                 CTCTTCCACA CCAACTTCTA CGACACTGTG GGCACAATCC AGCTTATCAA 
               
               
                   
               
               
                 CGACCACGTC AAGAAGGAAA CTCGAGGGAA GATTGTGGAT TTGGTCAGTG 
               
               
                   
               
               
                 AGCTCAAGAA GGACGTCTTG ATGGTGCTGG TGAATTACAT TTACTTCAAA 
               
               
                   
               
               
                 GCCCTGTGGG AGAAACCATT CATTTCCTCA AGGACCACTC CCAAAGACTT 
               
               
                   
               
               
                 CTATGTTGAT GAGAACACAA CAGTCCGGGT GCCCATGATG CTGCAGGACC 
               
               
                   
               
               
                 AGGAGCATCA CTGGTATCTT CATGACAGAT ACTTGCCCTG CTCGGTGCTA 
               
               
                   
               
               
                 CGGATGGATT ACAAAGGAGA CGCAACCGTG TTTTTCATTC TCCCTAACCA 
               
               
                   
               
               
                 AGGCAAAATG AGGGAGATTG AAGAGGTTCT GACTCCAGAG ATGCTAATGA 
               
               
                   
               
               
                 GGTGGAACAA CTTGTTGCGG AAGAGGAATT TTTACAAGAA GCTAGAGTTG 
               
               
                   
               
               
                 CATCTTCCCA AGTTCTCCAT TTCTGGCTCC TATGTATTAG ATCAGATTTT 
               
               
                   
               
               
                 GCCCAGGCTG GGCTTCACGG ATCTGTTCTC CAAGTGGGCT GACTTATCCG 
               
               
                   
               
               
                 GCATCACCAA ACAGCAAAAA CTGGAGGCAT CCAAAAGTTT CCACAAGGCC 
               
               
                   
               
               
                 ACCTTGGACG TGGATGAGGC TGGCACCGAG GCTGCAGCAG CCACCAGCTT 
               
               
                   
               
               
                 CGCGATCAAA TTCTTCTCTG CCCAGACCAA TCGCCACATC CTGCGATTCA 
               
               
                   
               
               
                 ACCGGCCCTT CCTTGTGGTG ATCTTTTCCA CCAGCACCCA GAGTGTCCTC 
               
               
                   
               
               
                 TTTCTGGGCA AGGTCGTCGA CCCCACGAAA CCATAG 
               
               
                   
               
               
                 SEQ ID No. 14 
                   
               
               
                 SerpinA4 transcript variant 2 (Human) Protein 
                   
               
               
                 MHLIDYLLLLLVGLLALSHGQLHVEHDGESCSNSSHQQILETGEGSPSLKIAPANA 
               
               
                   
               
               
                 DFAFRFYYLIASETPGKNIFFSPLSISAAYAMLSLGACSHSRSQILEGLGFNLTELSE 
               
               
                   
               
               
                 SDVHRGFQHLLHTLNLPGHGLETRVGSALFLSHNLKFLAKFLNDTMAVYEAKLF 
               
               
                   
               
               
                 HTNFYDTVGTIQLINDHVKKETRGKIVDLVSELKKDVLMVLVNYIYFKALWEKP 
               
               
                   
               
               
                 FISSRTTPKDFYVDENTTVRVPMMLQDQEHHWYLHDRYLPCSVLRMDYKGDAT 
               
               
                   
               
               
                 VFFILPNQGKMREIEEVLTPEMLMRWNNLLRKRNFYKKLELHLPKFSISGSYVLD 
               
               
                   
               
               
                 QILPRLGFTDLFSKWADLSGITKQQKLEASKSFHKATLDVDEAGTEAAAATSFAI 
               
               
                   
               
               
                 KFFSAQTNRHILRFNRPFLVVIFSTSTQSVLFLGKVVDPTKP 
               
               
                   
               
               
                 SEQ ID No. 15 
                   
               
               
                 SerpinA4 transcript variant 2 (Human) cDNA 
                   
               
               
                 ATGCATCT TATCGACTAC CTGCTCCTCC TGCTGGTTGG ACTACTGGCC 
               
               
                   
               
               
                 CTTTCTCATG GCCAGCTGCA CGTTGAGCAT GATGGTGAGA GTTGCAGTAA 
               
               
                   
               
               
                 CAGCTCCCAC CAGCAGATTC TGGAGACAGG TGAGGGCTCC CCCAGCCTCA 
               
               
                   
               
               
                 AGATAGCCCC TGCCAATGCT GACTTTGCCT TCCGCTTCTA CTACCTGATC 
               
               
                   
               
               
                 GCTTCGGAGA CCCCGGGGAA GAACATCTTT TTCTCCCCGC TGAGCATCTC 
               
               
                   
               
               
                 GGCGGCCTAC GCCATGCTTT CCCTGGGGGC CTGCTCACAC AGCCGCAGCC 
               
               
                   
               
               
                 AGATCCTTGA GGGCCTGGGC TTCAACCTCA CCGAGCTGTC TGAGTCCGAT 
               
               
                   
               
               
                 GTCCATAGGG GCTTCCAGCA CCTCCTGCAC ACTCTCAACC TCCCCGGCCA 
               
               
                   
               
               
                 TGGGCTGGAA ACACGCGTGG GCAGTGCTCT GTTCCTGAGC CACAACCTGA 
               
               
                   
               
               
                 AGTTCCTTGC AAAATTCCTG AATGACACCA TGGCCGTCTA TGAGGCTAAA 
               
               
                   
               
               
                 CTCTTCCACA CCAACTTCTA CGACACTGTG GGCACAATCC AGCTTATCAA 
               
               
                   
               
               
                 CGACCACGTC AAGAAGGAAA CTCGAGGGAA GATTGTGGAT TTGGTCAGTG 
               
               
                   
               
               
                 AGCTCAAGAA GGACGTCTTG ATGGTGCTGG TGAATTACAT TTACTTCAAA 
               
               
                   
               
               
                 GCCCTGTGGG AGAAACCATT CATTTCCTCA AGGACCACTC CCAAAGACTT 
               
               
                   
               
               
                 CTATGTTGAT GAGAACACAA CAGTCCGGGT GCCCATGATG CTGCAGGACC 
               
               
                   
               
               
                 AGGAGCATCA CTGGTATCTT CATGACAGAT ACTTGCCCTG CTCGGTGCTA 
               
               
                   
               
               
                 CGGATGGATT ACAAAGGAGA CGCAACCGTG TTTTTCATTC TCCCTAACCA 
               
               
                   
               
               
                 AGGCAAAATG AGGGAGATTG AAGAGGTTCT GACTCCAGAG ATGCTAATGA 
               
               
                   
               
               
                 GGTGGAACAA CTTGTTGCGG AAGAGGAATT TTTACAAGAA GCTAGAGTTG 
               
               
                   
               
               
                 CATCTTCCCA AGTTCTCCAT TTCTGGCTCC TATGTATTAG ATCAGATTTT 
               
               
                   
               
               
                 GCCCAGGCTG GGCTTCACGG ATCTGTTCTC CAAGTGGGCT GACTTATCCG 
               
               
                   
               
               
                 GCATCACCAA ACAGCAAAAA CTGGAGGCAT CCAAAAGTTT CCACAAGGCC 
               
               
                   
               
               
                 ACCTTGGACG TGGATGAGGC TGGCACCGAG GCTGCAGCAG CCACCAGCTT 
               
               
                   
               
               
                 CGCGATCAAA TTCTTCTCTG CCCAGACCAA TCGCCACATC CTGCGATTCA 
               
               
                   
               
               
                 ACCGGCCCTT CCTTGTGGTG ATCTTTTCCA CCAGCACCCA GAGTGTCCTC 
               
               
                   
               
               
                 TTTCTGGGCA AGGTCGTCGA CCCCACGAAA CCATAG 
               
               
                   
               
               
                 SEQ ID No. 16 
                   
               
               
                 SerpinA4 transcript variant 1 (Human) Protein 
                   
               
               
                 MPGDPEKPPPGTHSWYRAALTEGQGLLAANPGLRVQRMHLIDYLLLLLVGLLAL 
               
               
                   
               
               
                 SHGQLHVEHDGESCSNSSHQQILETGEGSPSLKIAPANADFAFRFYYLIASETPGK 
               
               
                   
               
               
                 NIFFSPLSISAAYAMLSLGACSHSRSQILEGLGFNLTELSESDVHRGFQHLLHTLNL 
               
               
                   
               
               
                 PGHGLETRVGSALFLSHNLKFLAKFLNDTMAVYEAKLFHTNFYDTVGTIQLINDH 
               
               
                   
               
               
                 VKKETRGKIVDLVSELKKDVLMVLVNYIYFKALWEKPFISSRTTPKDFYVDENT 
               
               
                   
               
               
                 TVRVPMMLQDQEHHWYLHDRYLPCSVLRMDYKGDATVFFILPNQGKMREIEEV 
               
               
                   
               
               
                 LTPEMLMRWNNLLRKRNFYKKLELHLPKFSISGSYVLDQILPRLGFTDLFSKWAD 
               
               
                   
               
               
                 LSGITKQQKLEASKSFHKATLDVDEAGTEAAAATSFAIKFFSAQTNRHILRFNRPF 
               
               
                   
               
               
                 LVVIFSTSTQSVLFLGKVVDPTKP 
               
               
                   
               
               
                 SEQ ID No. 17 
                   
               
               
                 SerpinA4 transcript variant 1 (Human) cDNA 
                   
               
               
                 ATGC CCGGAGACCC AGAAAAGCCT CCCCCAGGGA CACACAGCTG 
               
               
                   
               
               
                 GTACAGGGCG GCACTGACTG AGGGCCAAGG TCTTCTGGCT GCCAATCCAG 
               
               
                   
               
               
                 GCCTGAGAGT GCAGAGGATG CATCTTATCG ACTACCTGCT CCTCCTGCTG 
               
               
                   
               
               
                 GTTGGACTAC TGGCCCTTTC TCATGGCCAG CTGCACGTTG AGCATGATGG 
               
               
                   
               
               
                 TGAGAGTTGC AGTAACAGCT CCCACCAGCA GATTCTGGAG ACAGGTGAGG 
               
               
                   
               
               
                 GCTCCCCCAG CCTCAAGATA GCCCCTGCCA ATGCTGACTT TGCCTTCCGC 
               
               
                   
               
               
                 TTCTACTACC TGATCGCTTC GGAGACCCCG GGGAAGAACA TCTTTTTCTC 
               
               
                   
               
               
                 CCCGCTGAGC ATCTCGGCGGCCTACGCCAT GCTTTCCCTG GGGGCCTGCT 
               
               
                   
               
               
                 CACACAGCCG CAGCCAGATC CTTGAGGGCCTGGGCTTCAA CCTCACCGAG 
               
               
                   
               
               
                 CTGTCTGAGT CCGATGTCCA TAGGGGCTTC CAGCACCTCCTGCACACTCT 
               
               
                   
               
               
                 CAACCTCCCC GGCCATGGGC TGGAAACACG CGTGGGCAGT GCTCTGTTCC 
               
               
                   
               
               
                 TGAGCCACAA CCTGAAGTTC CTTGCAAAAT TCCTGAATGA CACCATGGCC 
               
               
                   
               
               
                 GTCTATGAGGCTAAACTCTT CCACACCAAC TTCTACGACA CTGTGGGCAC 
               
               
                   
               
               
                 AATCCAGCTT ATCAACGACCACGTCAAGAA GGAAACTCGA GGGAAGATTG 
               
               
                   
               
               
                 TGGATTTGGT CAGTGAGCTC AAGAAGGACGTCTTGATGGT GCTGGTGAAT 
               
               
                   
               
               
                 TACATTTACT TCAAAGCCCT GTGGGAGAAA CCATTCATTTCCTCAAGGAC 
               
               
                   
               
               
                 CACTCCCAAA GACTTCTATG TTGATGAGAA CACAACAGTC CGGGTGCCCA 
               
               
                   
               
               
                 TGATGCTGCA GGACCAGGAG CATCACTGGT ATCTTCATGA CAGATACTTG 
               
               
                   
               
               
                 CCCTGCTCGGTGCTACGGAT GGATTACAAA GGAGACGCAA CCGTGTTTTT 
               
               
                   
               
               
                 CATTCTCCCT AACCAAGGCAAAATGAGGGA GATTGAAGAG GTTCTGACTC 
               
               
                   
               
               
                 CAGAGATGCT AATGAGGTGG AACAACTTGTTGCGGAAGAG GAATTTTTAC 
               
               
                   
               
               
                 AAGAAGCTAG AGTTGCATCT TCCCAAGTTC TCCATTTCTGGCTCCTATGT 
               
               
                   
               
               
                 ATTAGATCAG ATTTTGCCCA GGCTGGGCTT CACGGATCTG TTCTCCAAGT 
               
               
                   
               
               
                 GGGCTGACTT ATCCGGCATC ACCAAACAGC AAAAACTGGA GGCATCCAAA 
               
               
                   
               
               
                 AGTTTCCACAAGGCCACCTT GGACGTGGAT GAGGCTGGCA CCGAGGCTGC 
               
               
                   
               
               
                 AGCAGCCACC AGCTTCGCGATCAAATTCTT CTCTGCCCAG ACCAATCGCC 
               
               
                   
               
               
                 ACATCCTGCG ATTCAACCGG CCCTTCCTTGTGGTGATCTT TTCCACCAGC 
               
               
                   
               
               
                 ACCCAGAGTG TCCTCTTTCT GGGCAAGGTC GTCGACCCCACGAAACCATA G 
               
               
                   
               
               
                 SEQ ID No. 18 
                   
               
               
                 SerpinA5 (Human) Protein 
                   
               
               
                 MQLFLLLCLVLLSPQGASLHRHHPREMKKRVEDLHVGATVAPSSRRDFTFDLYR 
               
               
                   
               
               
                 ALASAAPSQSIFFSPVSISMSLAMLSLGAGSSTKMQILEGLGLNLQKSSEKELHRG 
               
               
                   
               
               
                 FQQLLQELNQPRDGFQLSLGNALFTDLVVDLQDTFVSAMKTLYLADTFPTNFRD 
               
               
                   
               
               
                 SAGAMKQINDYVAKQTKGKIVDLLKNLDSNAVVIMVNYIFFKAKWETSFNHKG 
               
               
                   
               
               
                 TQEQDFYVTSETVVRVPMMSREDQYHYLLDRNLSCRVVGVPYQGNATALFILPS 
               
               
                   
               
               
                 EGKMQQVENGLSEKTLRKWLKMFKKRQLELYLPKFSIEGSYQLEKVLPSLGISNV 
               
               
                   
               
               
                 FTSHADLSGISNHSNIQVSEMVHKAVVEVDESGTRAAAATGTIFTFRSARLNSQR 
               
               
                   
               
               
                 LVFNRPFLMFIVDNNILFLGKVNRP 
               
               
                   
               
               
                 SEQ ID No. 19 
                   
               
               
                 SerpinA5 (Human) cDNA 
                   
               
               
                 ATGCAGCTCTTCCTC CTCTTGTGCC TGGTGCTTCT CAGCCCTCAG 
               
               
                   
               
               
                 GGGGCCTCCC TTCACCGCCACCACCCCCGG GAGATGAAGA AGAGAGTCGA 
               
               
                   
               
               
                 GGACCTCCAT GTAGGTGCCA CGGTGGCCCCCAGCAGCAGA AGGGACTTTA 
               
               
                   
               
               
                 CCTTTGACCT CTACAGGGCC TTGGCTTCCG CTGCCCCCAGCCAGAGCATC 
               
               
                   
               
               
                 TTCTTCTCCC CTGTGAGCAT CTCCATGAGC CTGGCCATGC TCTCCCTGGG 
               
               
                   
               
               
                 GGCTGGGTCC AGCACAAAGA TGCAGATCCT GGAGGGCCTG GGCCTCAACC 
               
               
                   
               
               
                 TCCAGAAAAGCTCAGAGAAG GAGCTGCACA GAGGCTTTCA GCAGCTCCTT 
               
               
                   
               
               
                 CAGGAACTCA ACCAGCCCAGAGATGGCTTC CAGCTGAGCC TCGGCAATGC 
               
               
                   
               
               
                 CCTTTTCACC GACCTGGTGG TAGACCTGCAGGACACCTTC GTAAGTGCCA 
               
               
                   
               
               
                 TGAAGACGCT GTACCTGGCA GACACTTTCC CTACCAACTTTAGGGACTCT 
               
               
                   
               
               
                 GCAGGGGCCA TGAAGCAGAT CAATGATTAT GTGGCAAAGC AAACGAAGGG 
               
               
                   
               
               
                 CAAGATTGTG GACTTGCTTA AGAACCTCGA TAGCAATGCG GTCGTGATCA 
               
               
                   
               
               
                 TGGTGAATTACATCTTCTTT AAAGCTAAGT GGGAGACAAG CTTCAACCAC 
               
               
                   
               
               
                 AAAGGCACCC AAGAGCAAGACTTCTACGTG ACCTCGGAGA CTGTGGTGCG 
               
               
                   
               
               
                 GGTACCCATG ATGAGCCGCG AGGATCAGTATCACTACCTC CTGGACCGGA 
               
               
                   
               
               
                 ACCTCTCCTG CAGGGTGGTG GGGGTCCCCT ACCAAGGCAATGCCACGGCT 
               
               
                   
               
               
                 TTGTTCATTC TCCCCAGTGA GGGAAAGATG CAGCAGGTGG AGAATGGACT 
               
               
                   
               
               
                 GAGTGAGAAA ACGCTGAGGA AGTGGCTTAA GATGTTCAAA AAGAGGCAGC 
               
               
                   
               
               
                 TCGAGCTTTACCTTCCCAAA TTCTCCATTG AGGGCTCCTA TCAGCTGGAG 
               
               
                   
               
               
                 AAAGTCCTCC CCAGTCTGGGGATCAGTAAC GTCTTCACCT CCCATGCTGA 
               
               
                   
               
               
                 TCTGTCCGGC ATCAGCAACC ACTCAAATATCCAGGTGTCT GAGATGGTGC 
               
               
                   
               
               
                 ACAAAGCTGT GGTGGAGGTG GACGAGTCGG GAACCAGAGCAGCGGCAGCC 
               
               
                   
               
               
                 ACGGGGACAA TATTCACTTT CAGGTCGGCC CGCCTGAACT CTCAGAGGCT 
               
               
                   
               
               
                 AGTGTTCAAC AGGCCCTTTC TGATGTTCAT TGTGGATAAC AACATCCTCT 
               
               
                   
               
               
                 TCCTTGGCAAAGTGAACCGC CCCTGA 
               
               
                   
               
               
                 SEQ ID No. 20 
                   
               
               
                 SerpinA9 transcript variant 4 (Human) Protein 
                   
               
               
                 MGSALFVKKELQLQANFLGNVKRLYEAEVFSTDFSNPSIAQARINSHVKKKTQG 
               
               
                   
               
               
                 KVVDIIQGLDLLTAMVLVNHIFFKAKWEKPFHPEYTRKNFPFLVGEQVTVHVPM 
               
               
                   
               
               
                 MHQKEQFAFGVDTELNCFVLQMDYKGDAVAFFVLPSKGKMRQLEQALSARTL 
               
               
                   
               
               
                 RKWSHSLQKRWIEVFIPRFSISASYNLETILPKMGIQNVFDKNADFSGIAKRDSLQ 
               
               
                   
               
               
                 VSKATHKAVLDVSEEGTEATAATTTKFIVRSKDGPSYFTVSFNRTFLMMITNKAT 
               
               
                   
               
               
                 DGILFLGKVENPTKS 
               
               
                   
               
               
                 SEQ ID No. 21 
                   
               
               
                 SerpinA9 transcript variant 4 (Human) cDNA 
                   
               
               
                 ATGGG AAGTGCCCTC TTCGTCAAGA AGGAGCTGCA GCTGCAGGCA 
               
               
                   
               
               
                 AATTTCTTGG GCAATGTCAA GAGGCTGTAT GAAGCAGAAG TCTTTTCTAC 
               
               
                   
               
               
                 AGATTTCTCCAACCCCTCCA TTGCCCAGGC GAGGATCAAC AGCCATGTGA 
               
               
                   
               
               
                 AAAAGAAGAC CCAAGGGAAGGTTGTAGACA TAATCCAAGG CCTTGACCTT 
               
               
                   
               
               
                 CTGACGGCCA TGGTTCTGGT GAACCACATTTTCTTTAAAG CCAAGTGGGA 
               
               
                   
               
               
                 GAAGCCCTTT CACCCTGAAT ATACAAGAAA GAACTTCCCATTCCTGGTGG 
               
               
                   
               
               
                 GCGAGCAGGT CACTGTGCAT GTCCCCATGA TGCACCAGAA AGAGCAGTTC 
               
               
                   
               
               
                 GCTTTTGGGG TGGATACAGA GCTGAACTGC TTTGTGCTGC AGATGGATTA 
               
               
                   
               
               
                 CAAGGGAGATGCCGTGGCCT TCTTTGTCCT CCCTAGCAAG GGCAAGATGA 
               
               
                   
               
               
                 GGCAACTGGA ACAGGCCTTGTCAGCCAGAA CACTGAGAAA GTGGAGCCAC 
               
               
                   
               
               
                 TCACTCCAGA AAAGGTGGAT AGAGGTGTTCATCCCCAGAT TTTCCATTTC 
               
               
                   
               
               
                 TGCCTCCTAC AATCTGGAAA CCATCCTCCC GAAGATGGGCATCCAAAATG 
               
               
                   
               
               
                 TCTTTGACAA AAATGCTGAT TTTTCTGGAA TTGCAAAGAG AGACTCCCTG 
               
               
                   
               
               
                 CAGGTTTCTA AAGCAACCCA CAAGGCTGTG CTGGATGTCA GTGAAGAGGG 
               
               
                   
               
               
                 CACTGAGGCCACAGCAGCTA CCACCACCAA GTTCATAGTC CGATCGAAGG 
               
               
                   
               
               
                 ATGGCCCCTC TTACTTCACTGTCTCCTTCA ATAGGACCTT CCTGATGATG 
               
               
                   
               
               
                 ATTACAAATA AAGCCACAGA CGGTATTCTCTTTCTAGGGA AAGTGGAAAA 
               
               
                   
               
               
                 TCCCACTAAA TCCTAG 
               
               
                   
               
               
                 SEQ ID No. 22 
                   
               
               
                 SerpinA9 transcript variant 3 (Human) Protein 
                   
               
               
                 MRSAGGRGEIKVRRELQPSKQVSGLTNHARTGQEKRNLQRLVLETPSQNIFFSPV 
               
               
                   
               
               
                 SVSTSLAMLSLGAHSVTKTQILQGLGFNLTHTPESAIHQGFQHLVHSLTVPSKDLT 
               
               
                   
               
               
                 LKMGSALFVKKELQLQANFLGNVKRLYEAEVFSTDFSNPSIAQARINSHVKKKT 
               
               
                   
               
               
                 QGKVVDIIQGLDLLTAMVLVNHIFFKAKWEKPFHPEYTRKNFPFLVGEQVTVH 
               
               
                   
               
               
                 VPMMHQKEQFAFGVDTELNCFVLQMDYKGDAVAFFVLPSKGKMRQLEQALSA 
               
               
                   
               
               
                 RTLRKWSHSLQKRWIEVFIPRFSISASYNLETILPKMGIQNVFDKNADFSGIAKRD 
               
               
                   
               
               
                 SLQVSKATHKAVLDVSEEGTEATAATTTKFIVRSKDGPSYFTVSFNRTFLMMITN 
               
               
                   
               
               
                 KATDGILFLGKVENPTKS 
               
               
                   
               
               
                 SEQ ID No. 23 
                   
               
               
                 SerpinA9 transcript variant 3 (Human) cDNA 
                   
               
               
                 ATGAGATCAGCTGGAGGGAGAGGAGAGATTA AAGTGAGGAGAGAGCTACAA 
               
               
                   
               
               
                 CCAAGTAAGC AAGTGTCAGG GCTCACCAAC CATGCAAGGA CAGGGCAGGA 
               
               
                   
               
               
                 GAAGAGGAAC CTGCAAAGGC TGGTTTTGGA GACCCCGAGT CAGAACATCT 
               
               
                   
               
               
                 TCTTCTCCCCTGTGAGTGTC TCCACTTCCC TGGCCATGCT CTCCCTTGGG 
               
               
                   
               
               
                 GCCCACTCAG TCACCAAGACCCAGATTCTC CAGGGCCTGG GCTTCAACCT 
               
               
                   
               
               
                 CACACACACA CCAGAGTCTG CCATCCACCAGGGCTTCCAG CACCTGGTTC 
               
               
                   
               
               
                 ACTCACTGAC TGTTCCCAGC AAAGACCTGA CCTTGAAGATGGGAAGTGCC 
               
               
                   
               
               
                 CTCTTCGTCA AGAAGGAGCT GCAGCTGCAG GCAAATTTCT TGGGCAATGT 
               
               
                   
               
               
                 CAAGAGGCTG TATGAAGCAG AAGTCTTTTC TACAGATTTC TCCAACCCCT 
               
               
                   
               
               
                 CCATTGCCCAGGCGAGGATC AACAGCCATG TGAAAAAGAA GACCCAAGGG 
               
               
                   
               
               
                 AAGGTTGTAG ACATAATCCAAGGCCTTGAC CTTCTGACGG CCATGGTTCT 
               
               
                   
               
               
                 GGTGAACCAC ATTTTCTTTA AAGCCAAGTGGGAGAAGCCC TTTCACCCTG 
               
               
                   
               
               
                 AATATACAAG AAAGAACTTC CCATTCCTGG TGGGCGAGCAGGTCACTGTG 
               
               
                   
               
               
                 CATGTCCCCA TGATGCACCA GAAAGAGCAG TTCGCTTTTG GGGTGGATAC 
               
               
                   
               
               
                 AGAGCTGAAC TGCTTTGTGC TGCAGATGGA TTACAAGGGA GATGCCGTGG 
               
               
                   
               
               
                 CCTTCTTTGTCCTCCCTAGC AAGGGCAAGA TGAGGCAACT GGAACAGGCC 
               
               
                   
               
               
                 TTGTCAGCCA GAACACTGAGAAAGTGGAGC CACTCACTCC AGAAAAGGTG 
               
               
                   
               
               
                 GATAGAGGTG TTCATCCCCA GATTTTCCATTTCTGCCTCC TACAATCTGG 
               
               
                   
               
               
                 AAACCATCCT CCCGAAGATG GGCATCCAAA ATGTCTTTGACAAAAATGCT 
               
               
                   
               
               
                 GATTTTTCTG GAATTGCAAA GAGAGACTCC CTGCAGGTTT CTAAAGCAAC 
               
               
                   
               
               
                 CCACAAGGCT GTGCTGGATG TCAGTGAAGA GGGCACTGAG GCCACAGCAG 
               
               
                   
               
               
                 CTACCACCACCAAGTTCATA GTCCGATCGA AGGATGGCCC CTCTTACTTC 
               
               
                   
               
               
                 ACTGTCTCCT TCAATAGGACCTTCCTGATG ATGATTACAA ATAAAGCCAC 
               
               
                   
               
               
                 AGACGGTATT CTCTTTCTAG GGAAAGTGGAAAATCCCACT AAATCCTAG 
               
               
                   
               
               
                 SEQ ID No. 24 
                   
               
               
                 SerpinA9 transcript variant 2 (Human) Protein 
                   
               
               
                 MQGQGRRRGTCKDIFCSKMASYLYGVLFAVGLCAPIYCVSPANAPSAYPRPSST 
               
               
                   
               
               
                 KSTPASQVYSLNTDFAFRLYRRLVLETPSQNIFFSPARINSHVKKKTQGKVVDIIQ 
               
               
                   
               
               
                 GLDLLTAMVLVNHIFFKAKWEKPFHPEYTRKNFPFLVGEQVTVHVPMMHQKEQ 
               
               
                   
               
               
                 FAFGVDTELNCFVLQMDYKGDAVAFFVLPSKGKMRQLEQALSARTLRKWSHSL 
               
               
                   
               
               
                 QKRWIEVFIPRFSISASYNLETILPKMGIQNVFDKNADFSGIAKRDSLQVSKATHK 
               
               
                   
               
               
                 AVLDVSEEGTEATAATTTKFIVRSKDGPSYFTVSFNRTFLMMITNKATDGILFLGK 
               
               
                   
               
               
                 VENPTKS 
               
               
                   
               
               
                 SEQ ID No. 25 
                   
               
               
                 SerpinA9 transcript variant 2 (Human) cDNA 
                   
               
               
                 ATGCAAGGA CAGGGCAGGAGAAGAGGAAC CTGCAAAGAC ATATTTTGTT 
               
               
                   
               
               
                 CCAAAATGGC ATCTTACCTT TATGGAGTACTCTTTGCTGT TGGCCTCTGT 
               
               
                   
               
               
                 GCTCCAATCT ACTGTGTGTC CCCGGCCAAT GCCCCCAGTGCATACCCCCG 
               
               
                   
               
               
                 CCCTTCCTCC ACAAAGAGCA CCCCTGCCTC ACAGGTGTAT TCCCTCAACA 
               
               
                   
               
               
                 CCGACTTTGC CTTCCGCCTA TACCGCAGGC TGGTTTTGGA GACCCCGAGT 
               
               
                   
               
               
                 CAGAACATCTTCTTCTCCCC TGCGAGGATC AACAGCCATG TGAAAAAGAA 
               
               
                   
               
               
                 GACCCAAGGG AAGGTTGTAGACATAATCCA AGGCCTTGAC CTTCTGACGG 
               
               
                   
               
               
                 CCATGGTTCT GGTGAACCAC ATTTTCTTTAAAGCCAAGTG GGAGAAGCCC 
               
               
                   
               
               
                 TTTCACCCTG AATATACAAG AAAGAACTTC CCATTCCTGGTGGGCGAGCA 
               
               
                   
               
               
                 GGTCACTGTG CATGTCCCCA TGATGCACCA GAAAGAGCAG TTCGCTTTTG 
               
               
                   
               
               
                 GGGTGGATAC AGAGCTGAAC TGCTTTGTGC TGCAGATGGA TTACAAGGGA 
               
               
                   
               
               
                 GATGCCGTGGCCTTCTTTGT CCTCCCTAGC AAGGGCAAGA TGAGGCAACT 
               
               
                   
               
               
                 GGAACAGGCC TTGTCAGCCAGAACACTGAG AAAGTGGAGC CACTCACTCC 
               
               
                   
               
               
                 AGAAAAGGTG GATAGAGGTG TTCATCCCCAGATTTTCCAT TTCTGCCTCC 
               
               
                   
               
               
                 TACAATCTGG AAACCATCCT CCCGAAGATG GGCATCCAAAATGTCTTTGA 
               
               
                   
               
               
                 CAAAAATGCT GATTTTTCTG GAATTGCAAA GAGAGACTCC CTGCAGGTTT 
               
               
                   
               
               
                 CTAAAGCAAC CCACAAGGCT GTGCTGGATG TCAGTGAAGA GGGCACTGAG 
               
               
                   
               
               
                 GCCACAGCAGCTACCACCAC CAAGTTCATA GTCCGATCGA AGGATGGCCC 
               
               
                   
               
               
                 CTCTTACTTC ACTGTCTCCTTCAATAGGAC CTTCCTGATG ATGATTACAA 
               
               
                   
               
               
                 ATAAAGCCAC AGACGGTATT CTCTTTCTAGGGAAAGTGGA AAATCCCACT 
               
               
                   
               
               
                 AAATCCTAG 
               
               
                   
               
               
                 SEQ ID No. 26 
                   
               
               
                 SerpinA9 transcript variant 1 (Human) Protein 
                   
               
               
                 MQGQGRRRGTCKDIFCSKMASYLYGVLFAVGLCAPIYCVSPANAPSAYPRPSST 
               
               
                   
               
               
                 KSTPASQVYSLNTDFAFRLYRRLVLETPSQNIFFSPVSVSTSLAMLSLGAHSVTKT 
               
               
                   
               
               
                 QILQGLGFNLTHTPESAIHQGFQHLVHSLTVPSKDLTLKMGSALFVKKELQLQAN 
               
               
                   
               
               
                 FLGNVKRLYEAEVFSTDFSNPSIAQARINSHVKKKTQGKVVDIIQGLDLLTAMVL 
               
               
                   
               
               
                 VNHIFFKAKWEKPFHPEYTRKNFPFLVGEQVTVHVPMMHQKEQFAFGVDTELN 
               
               
                   
               
               
                 CFVLQMDYKGDAVAFFVLPSKGKMRQLEQALSARTLRKWSHSLQKRWIEVFIPR 
               
               
                   
               
               
                 FSISASYNLETILPKMGIQNVFDKNADFSGIAKRDSLQVSKATHKAVLDVSEEGTE 
               
               
                   
               
               
                 ATAATTTKFIVRSKDGPSYFTVSFNRTFLMMITNKATDGILFLGKVENPTKS 
               
               
                   
               
               
                 SEQ ID No. 27 
                   
               
               
                 SerpinA9 transcript variant 1 (Human) cDNA 
                   
               
               
                 ATGCAAGGA CAGGGCAGGAGAAGAGGAAC CTGCAAAGAC ATATTTTGTT 
               
               
                   
               
               
                 CCAAAATGGC ATCTTACCTT TATGGAGTACTCTTTGCTGT TGGCCTCTGT 
               
               
                   
               
               
                 GCTCCAATCT ACTGTGTGTC CCCGGCCAAT GCCCCCAGTGCATACCCCCG 
               
               
                   
               
               
                 CCCTTCCTCC ACAAAGAGCA CCCCTGCCTC ACAGGTGTAT TCCCTCAACA 
               
               
                   
               
               
                 CCGACTTTGC CTTCCGCCTA TACCGCAGGC TGGTTTTGGA GACCCCGAGT 
               
               
                   
               
               
                 CAGAACATCTTCTTCTCCCC TGTGAGTGTC TCCACTTCCC TGGCCATGCT 
               
               
                   
               
               
                 CTCCCTTGGG GCCCACTCAGTCACCAAGAC CCAGATTCTC CAGGGCCTGG 
               
               
                   
               
               
                 GCTTCAACCT CACACACACA CCAGAGTCTGCCATCCACCA GGGCTTCCAG 
               
               
                   
               
               
                 CACCTGGTTC ACTCACTGAC TGTTCCCAGC AAAGACCTGACCTTGAAGAT 
               
               
                   
               
               
                 GGGAAGTGCC CTCTTCGTCA AGAAGGAGCT GCAGCTGCAG GCAAATTTCT 
               
               
                   
               
               
                 TGGGCAATGT CAAGAGGCTG TATGAAGCAG AAGTCTTTTC TACAGATTTC 
               
               
                   
               
               
                 TCCAACCCCTCCATTGCCCA GGCGAGGATC AACAGCCATG TGAAAAAGAA 
               
               
                   
               
               
                 GACCCAAGGG AAGGTTGTAGACATAATCCA AGGCCTTGAC CTTCTGACGG 
               
               
                   
               
               
                 CCATGGTTCT GGTGAACCAC ATTTTCTTTAAAGCCAAGTG GGAGAAGCCC 
               
               
                   
               
               
                 TTTCACCCTG AATATACAAG AAAGAACTTC CCATTCCTGGTGGGCGAGCA 
               
               
                   
               
               
                 GGTCACTGTG CATGTCCCCA TGATGCACCA GAAAGAGCAG TTCGCTTTTG 
               
               
                   
               
               
                 GGGTGGATAC AGAGCTGAAC TGCTTTGTGC TGCAGATGGA TTACAAGGGA 
               
               
                   
               
               
                 GATGCCGTGGCCTTCTTTGT CCTCCCTAGC AAGGGCAAGA TGAGGCAACT 
               
               
                   
               
               
                 GGAACAGGCC TTGTCAGCCAGAACACTGAG AAAGTGGAGC CACTCACTCC 
               
               
                   
               
               
                 AGAAAAGGTG GATAGAGGTG TTCATCCCCAGATTTTCCAT TTCTGCCTCC 
               
               
                   
               
               
                 TACAATCTGG AAACCATCCT CCCGAAGATG GGCATCCAAAATGTCTTTGA 
               
               
                   
               
               
                 CAAAAATGCT GATTTTTCTG GAATTGCAAA GAGAGACTCC CTGCAGGTTT 
               
               
                   
               
               
                 CTAAAGCAAC CCACAAGGCT GTGCTGGATG TCAGTGAAGA GGGCACTGAG 
               
               
                   
               
               
                 GCCACAGCAGCTACCACCAC CAAGTTCATA GTCCGATCGA AGGATGGCCC 
               
               
                   
               
               
                 CTCTTACTTC ACTGTCTCCTTCAATAGGAC CTTCCTGATG ATGATTACAA 
               
               
                   
               
               
                 ATAAAGCCAC AGACGGTATT CTCTTTCTAGGGAAAGTGGA AAATCCCACT 
               
               
                   
               
               
                 AAATCCTAG 
               
               
                   
               
               
                 SEQ ID No. 28 
                   
               
               
                 SerpinA10 transcript variant 1 (Human) Protein 
                   
               
               
                 MKVVPSLLLSVLLAQVWLVPGLAPSPQSPETPAPQNQTSRVVQAPKEEEEDEQE 
               
               
                   
               
               
                 ASEEKASEEEKAWLMASRQQLAKETSNFGFSLLRKISMRHDGNMVFSPFGMSLA 
               
               
                   
               
               
                 MTGLMLGATGPTETQIKRGLHLQALKPTKPGLLPSLFKGLRETLSRNLELGLTQG 
               
               
                   
               
               
                 SFAFIHKDFDVKETFFNLSKRYFDTECVPMNFRNASQAKRLMNHYINKETRGKIP 
               
               
                   
               
               
                 KLFDEINPETKLILVDYILFKGKWLTPFDPVFTEVDTFHLDKYKTIKVPMMYGAG 
               
               
                   
               
               
                 KFASTFDKNFRCHVLKLPYQGNATMLVVLMEKMGDHLALEDYLTTDLVETWLR 
               
               
                   
               
               
                 NMKTRNMEVFFPKFKLDQKYEMHELLRQMGIRRIFSPFADLSELSATGRNLQVS 
               
               
                   
               
               
                 RVLQRTVIEVDERGTEAVAGILSEITAYSMPPVIKVDRPFHFMIYEETSGMLLFLG 
               
               
                   
               
               
                 RVVNPTLL 
               
               
                   
               
               
                 SEQ ID No. 29 
                   
               
               
                 SerpinA10 transcript variant 1 (Human) cDNA 
                   
               
               
                 ATGA AGGTGGTGCCAAGTCTCCTG CTCTCCGTCC TCCTGGCACA 
               
               
                   
               
               
                 GGTGTGGCTG GTACCCGGCT TGGCCCCCAGTCCTCAGTCG CCAGAGACCC 
               
               
                   
               
               
                 CAGCCCCTCA GAACCAGACC AGCAGGGTAG TGCAGGCTCCCAAGGAGGAA 
               
               
                   
               
               
                 GAGGAAGATG AGCAGGAGGC CAGCGAGGAG AAGGCCAGTAGGAAGAGAA 
               
               
                   
               
               
                 AGCCTGGCTG ATGGCCAGCA GGCAGCAGCT TGCCAAGGAG ACTTCAAACT 
               
               
                   
               
               
                 AAGATCTCCA TGAGGCACGA TGGCAACATG 
               
               
                   
               
               
                 GTCTTCTCTC CATTTGGCATGTCCTTGGCC ATGACAGGCT TGATGCTGGG 
               
               
                   
               
               
                 GGCCACAGGG CCGACTGAAA CCCAGATCAAGAGAGGGCTC CACTTGCAGG 
               
               
                   
               
               
                 CCCTGAAGCC CACCAAGCCC GGGCTCCTGC CTTCCCTCTTTAAGGGACTC 
               
               
                   
               
               
                 AGAGAGACCC TCTCCCGCAA CCTGGAACTG GGCCTCACAC AGGGGAGTTT 
               
               
                   
               
               
                 TGCCTTCATC CACAAGGATT TTGATGTCAA AGAGACTTTC TTCAATTTAT 
               
               
                   
               
               
                 CCAAGAGGTATTTTGATACA GAGTGCGTGC CTATGAATTT TCGCAATGCC 
               
               
                   
               
               
                 TCACAGGCCA AAAGGCTCATGAATCATTAC ATTAACAAAG AGACTCGGGG 
               
               
                   
               
               
                 GAAAATTCCC AAACTGTTTG ATGAGATTAATCCTGAAACC AAATTAATTC 
               
               
                   
               
               
                 TTGTGGATTA CATCTTGTTC AAAGGGAAAT GGTTGACCCCATTTGACCCT 
               
               
                   
               
               
                 GTCTTCACCG AAGTCGACAC TTTCCACCTG GACAAGTACA AGACCATTAA 
               
               
                   
               
               
                 GGTGCCCATG ATGTACGGTG CAGGCAAGTT TGCCTCCACC TTTGACAAGA 
               
               
                   
               
               
                 ATTTTCGTTGTCATGTCCTC AAACTGCCCT ACCAAGGAAA TGCCACCATG 
               
               
                   
               
               
                 CTGGTGGTCC TCATGGAGAAAATGGGTGAC CACCTCGCCC TTGAAGACTA 
               
               
                   
               
               
                 CCTGACCACA GACTTGGTGG AGACATGGCTCAGAAACATG AAAACCAGAA 
               
               
                   
               
               
                 ACATGGAAGT TTTCTTTCCG AAGTTCAAGC TAGATCAGAAGTATGAGATG 
               
               
                   
               
               
                 CATGAGCTGC TTAGGCAGAT GGGAATCAGA AGAATCTTCT CACCCTTTGC 
               
               
                   
               
               
                 TGACCTTAGT GAACTCTCAG CTACTGGAAG AAATCTCCAA GTATCCAGGG 
               
               
                   
               
               
                 TTTTACAAAGAACAGTGATT GAAGTTGATG AAAGGGGCAC TGAGGCAGTG 
               
               
                   
               
               
                 GCAGGAATCT TGTCAGAAATTACTGCTTAT TCCATGCCTC CTGTCATCAA 
               
               
                   
               
               
                 AGTGGACCGG CCATTTCATT TCATGATCTATGAAGAAACC TCTGGAATGC 
               
               
                   
               
               
                 TTCTGTTTCT GGGCAGGGTG GTGAATCCGA CTCTCCTATAA 
               
               
                   
               
               
                 SEQ ID No. 30 
                   
               
               
                 SerpinA10 transcript variant 2 (Human) Protein 
                   
               
               
                 MKVVPSLLLSVLLAQVWLVPGLAPSPQSPETPAPQNQTSRVVQAPKEEEEDEQE 
               
               
                   
               
               
                 ASEEKASEEEKAWLMASRQQLAKETSNFGFSLLRKISMRHDGNMVFSPFGMSLA 
               
               
                   
               
               
                 MTGLMLGATGPTETQIKRGLHLQALKPTKPGLLPSLFKGLRETLSRNLELGLTQG 
               
               
                   
               
               
                 SFAFIHKDFDVKETFFNLSKRYFDTECVPMNFRNASQAKRLMNHYINKETRGKIP 
               
               
                   
               
               
                 KLFDEINPETKLILVDYILFKGKWLTPFDPVFTEVDTFHLDKYKTIKVPMMYGAG 
               
               
                   
               
               
                 KFASTFDKNFRCHVLKLPYQGNATMLVVLMEKMGDHLALEDYLTTDLVETWLR 
               
               
                   
               
               
                 NMKTRNMEVFFPKFKLDQKYEMHELLRQMGIRRIFSPFADLSELSATGRNLQVS 
               
               
                   
               
               
                 RVLQRTVIEVDERGTEAVAGILSEITAYSMPPVIKVDRPFHFMIYEETSGMLLFLG 
               
               
                   
               
               
                 RVVNPTLL 
               
               
                   
               
               
                 SEQ ID No. 31 
                   
               
               
                 SerpinA10 transcript variant 2 (Human) cDNA 
                   
               
               
                 ATGAAGG TGGTGCCAAG TCTCCTGCTC TCCGTCCTCC TGGCACAGGT 
               
               
                   
               
               
                 GTGGCTGGTA CCCGGCTTGG CCCCCAGTCC TCAGTCGCCA GAGACCCCAG 
               
               
                   
               
               
                 CCCCTCAGAACCAGACCAGC AGGGTAGTGC AGGCTCCCAA GGAGGAAGAG 
               
               
                   
               
               
                 GAAGATGAGC AGGAGGCCAGCGAGGAGAAG GCCAGTGAGGAAGAGAAAGC 
               
               
                   
               
               
                 CTGGCTGATG GCCAGCAGGC AGCAGCTTGCCAAGGAGACT TCAAACTTCG 
               
               
                   
               
               
                 GATTCAGCCT GCTGCGAAAG ATCTCCATGA GGCACGATGGCAACATGGTC 
               
               
                   
               
               
                 TTCTCTCCAT TTGGCATGTC CTTGGCCATG ACAGGCTTGA TGCTGGGGGC 
               
               
                   
               
               
                 CACAGGGCCG ACTGAAACCC AGATCAAGAG AGGGCTCCAC TTGCAGGCCC 
               
               
                   
               
               
                 TGAAGCCCACCAAGCCCGGG CTCCTGCCTT CCCTCTTTAA GGGACTCAGA 
               
               
                   
               
               
                 GAGACCCTCT CCCGCAACCTGGAACTGGGC CTCACACAGG GGAGTTTTGC 
               
               
                   
               
               
                 CTTCATCCAC AAGGATTTTG ATGTCAAAGAGACTTTCTTC AATTTATCCA 
               
               
                   
               
               
                 AGAGGTATTT TGATACAGAG TGCGTGCCTA TGAATTTTCGCAATGCCTCA 
               
               
                   
               
               
                 CAGGCCAAAA GGCTCATGAA TCATTACATT AACAAAGAGA CTCGGGGGAA 
               
               
                   
               
               
                 AATTCCCAAA CTGTTTGATG AGATTAATCC TGAAACCAAA TTAATTCTTG 
               
               
                   
               
               
                 TGGATTACATCTTGTTCAAA GGGAAATGGT TGACCCCATT TGACCCTGTC 
               
               
                   
               
               
                 TTCACCGAAG TCGACACTTTCCACCTGGAC AAGTACAAGA CCATTAAGGT 
               
               
                   
               
               
                 GCCCATGATG TACGGTGCAG GCAAGTTTGCCTCCACCTTT GACAAGAATT 
               
               
                   
               
               
                 TTCGTTGTCA TGTCCTCAAA CTGCCCTACC AAGGAAATGCCACCATGCTG 
               
               
                   
               
               
                 GTGGTCCTCA TGGAGAAAAT GGGTGACCAC CTCGCCCTTG AAGACTACCT 
               
               
                   
               
               
                 GACCACAGAC TTGGTGGAGA CATGGCTCAG AAACATGAAA ACCAGAAACA 
               
               
                   
               
               
                 TGGAAGTTTTCTTTCCGAAG TTCAAGCTAG ATCAGAAGTA TGAGATGCAT 
               
               
                   
               
               
                 GAGCTGCTTA GGCAGATGGGAATCAGAAGA ATCTTCTCAC CCTTTGCTGA 
               
               
                   
               
               
                 CCTTAGTGAA CTCTCAGCTA CTGGAAGAAATCTCCAAGTA TCCAGGGTTT 
               
               
                   
               
               
                 TACAAAGAAC AGTGATTGAA GTTGATGAAA GGGGCACTGAGGCAGTGGCA 
               
               
                   
               
               
                 GGAATCTTGT CAGAAATTAC TGCTTATTCC ATGCCTCCTG TCATCAAAGT 
               
               
                   
               
               
                 GGACCGGCCA TTTCATTTCA TGATCTATGA AGAAACCTCT GGAATGCTTC 
               
               
                   
               
               
                 TGTTTCTGGGCAGGGTGGTG AATCCGACTC TCCTATAA 
               
               
                   
               
               
                 SEQ ID No. 32 
                   
               
               
                 SerpinA12 transcript variant 1 (Human) Protein 
                   
               
               
                 MNPTLGLAIFLAVLLTVKGLLKPSFSPRNYKALSEVQGWKQRMAAKELARQNM 
               
               
                   
               
               
                 DLGFKLLKKLAFYNPGRNIFLSPLSISTAFSMLCLGAQDSTLDEIKQGFNFRKMPE 
               
               
                   
               
               
                 KDLHEGFHYIIHELTQKTQDLKLSIGNTLFIDQRLQPQRKFLEDAKNFYSAETILTN 
               
               
                   
               
               
                 FQNLEMAQKQINDFISQKTHGKINNLIENIDPGTVMLLANYIFFRARWKHEFDPN 
               
               
                   
               
               
                 VTKEEDFFLEKNSSVKVPMMFRSGIYQVGYDDKLSCTILEIPYQKNITAIFILPD 
               
               
                   
               
               
                 EGKLKHLEKGLQVDTFSRWKTLLSRRVVDVSVPRLHMTGTFDLKKTLSYIGVSKI 
               
               
                   
               
               
                 FEEHGDLTKIAPHRSLKVGEAVHKAELKMDERGTEGAAGTGAQTLPMETPLVVK 
               
               
                   
               
               
                 IDKPYLLLIYSEKIPSVLFLGKIVNPIGK 
               
               
                   
               
               
                 SEQ ID No. 33 
                   
               
               
                 SerpinA12 transcript variant 1 (Human) cDNA 
                   
               
               
                 ATGA ACCCCACACT AGGCCTGGCC ATTTTTCTGG CTGTTCTCCT 
               
               
                   
               
               
                 CACGGTGAAA GGTCTTCTAA AGCCGAGCTT CTCACCAAGG AATTATAAAG 
               
               
                   
               
               
                 CTTTGAGCGAGGTCCAAGGA TGGAAGCAAA GGATGGCAGC CAAGGAGCTT 
               
               
                   
               
               
                 GCAAGGCAGA ACATGGACTTAGGCTTTAAG CTGCTCAAGA AGCTGGCCTT 
               
               
                   
               
               
                 TTACAACCCT GGCAGGAACA TCTTCCTATCCCCCTTGAGC ATCTCTACAG 
               
               
                   
               
               
                 CTTTCTCCAT GCTGTGCCTG GGTGCCCAGG ACAGCACCCTGGACGAGATC 
               
               
                   
               
               
                 AAGCAGGGGT TCAACTTCAG AAAGATGCCA GAAAAAGATC TTCATGAGGG 
               
               
                   
               
               
                 CTTCCATTAC ATCATCCACG AGCTGACCCA GAAGACCCAG GACCTCAAAC 
               
               
                   
               
               
                 TGAGCATTGGGAACACGCTG TTCATTGACC AGAGGCTGCA GCCACAGCGT 
               
               
                   
               
               
                 AAGTTTTTGG AAGATGCCAAGAACTTTTAC AGTGCCGAAA CCATCCTTAC 
               
               
                   
               
               
                 CAACTTTCAG AATTTGGAAA TGGCTCAGAAGCAGATCAAT GACTTTATCA 
               
               
                   
               
               
                 GTCAAAAAAC CCATGGGAAA ATTAACAACC TGATCGAGAATATAGACCCC 
               
               
                   
               
               
                 GGCACTGTGA TGCTTCTTGC AAATTATATT TTCTTTCGAG CCAGGTGGAA 
               
               
                   
               
               
                 ACATGAGTTT GATCCAAATG TAACTAAAGA GGAAGATTTC TTTCTGGAGA 
               
               
                   
               
               
                 AAAACAGTTCAGTCAAGGTG CCCATGATGT TCCGTAGTGG CATATACCAA 
               
               
                   
               
               
                 GTTGGCTATG ACGATAAGCTCTCTTGCACC ATCCTGGAAA TACCCTACCA 
               
               
                   
               
               
                 GAAAAATATC ACAGCCATCT TCATCCTTCCTGATGAGGGC AAGCTGAAGC 
               
               
                   
               
               
                 ACTTGGAGAA GGGATTGCAG GTGGACACTT TCTCCAGATGGAAAACATTA 
               
               
                   
               
               
                 CTGTCACGCA GGGTCGTAGA CGTGTCTGTA CCCAGACTCC ACATGACGGG 
               
               
                   
               
               
                 CACCTTCGAC CTGAAGAAGA CTCTCTCCTA CATAGGTGTC TCCAAAATCT 
               
               
                   
               
               
                 TTGAGGAACATGGTGATCTC ACCAAGATCG CCCCTCATCG CAGCCTGAAA 
               
               
                   
               
               
                 GTGGGCGAGG CTGTGCACAAGGCTGAGCTG AAGATGGATG AGAGGGGTAC 
               
               
                   
               
               
                 GGAAGGGGCC GCTGGCACCG GAGCACAGACTCTGCCCATG GAGACACCAC 
               
               
                   
               
               
                 TCGTCGTCAA GATAGACAAA CCCTATCTGC TGCTGATTTACAGCGAGAAA 
               
               
                   
               
               
                 ATACCTTCCG TGCTCTTCCT GGGAAAGATT GTTAACCCTA TTGGAAAATA 
               
               
                   
               
               
                 A 
               
               
                   
               
               
                 SEQ ID No. 34 
                   
               
               
                 SerpinA12 transcript variant 2 (Human) Protein 
                   
               
               
                 MNPTLGLAIFLAVLLTVKGLLKPSFSPRNYKALSEVQGWKQRMAAKELARQNM 
               
               
                   
               
               
                 DLGFKLLKKLAFYNPGRNIFLSPLSISTAFSMLCLGAQDSTLDEIKQGFNFRKMPE 
               
               
                   
               
               
                 KDLHEGFHYIIHELTQKTQDLKLSIGNTLFIDQRLQPQRKFLEDAKNFYSAETILTN 
               
               
                   
               
               
                 FQNLEMAQKQINDFISQKTHGKINNLIENIDPGTVMLLANYIFFRARWKHEFDPN 
               
               
                   
               
               
                 VTKEEDFFLEKNSSVKVPMMFRSGIYQVGYDDKLSCTILEIPYQKNITAIFILPDEG 
               
               
                   
               
               
                 KLKHLEKGLQVDTFSRWKTLLSRRVVDVSVPRLHMTGTFDLKKTLSYIGVSKIFE 
               
               
                   
               
               
                 EHGDLTKIAPHRSLKVGEAVHKAELKMDERGTEGAAGTGAQTLPMETPLVVKID 
               
               
                   
               
               
                 KPYLLLIYSEKIPSVLFLGKIVNPIGK 
               
               
                   
               
               
                 SEQ ID No. 35 
                   
               
               
                 SerpinA12 transcript variant 2 (Human) cDNA 
                   
               
               
                 ATGAACC CCACACTAGGCCTGGCCATT TTTCTGGCTG TTCTCCTCAC 
               
               
                   
               
               
                 GGTGAAAGGT CTTCTAAAGC CGAGCTTCTCACCAAGGAAT TATAAAGCTT 
               
               
                   
               
               
                 TGAGCGAGGT CCAAGGATGG AAGCAAAGGA TGGCAGCCAAGGAGCTTGCA 
               
               
                   
               
               
                 AGGCAGAACA TGGACTTAGG CTTTAAGCTG CTCAAGAAGC TGGCCTTTTA 
               
               
                   
               
               
                 CAACCCTGGC AGGAACATCT TCCTATCCCC CTTGAGCATC TCTACAGCTT 
               
               
                   
               
               
                 TCTCCATGCTGTGCCTGGGT GCCCAGGACA GCACCCTGGA CGAGATCAAG 
               
               
                   
               
               
                 CAGGGGTTCA ACTTCAGAAAGATGCCAGAA AAAGATCTTC ATGAGGGCTT 
               
               
                   
               
               
                 CCATTACATC ATCCACGAGC TGACCCAGAAGACCCAGGAC CTCAAACTGA 
               
               
                   
               
               
                 GCATTGGGAA CACGCTGTTC ATTGACCAGA GGCTGCAGCCACAGCGTAAG 
               
               
                   
               
               
                 TTTTTGGAAG ATGCCAAGAA CTTTTACAGT GCCGAAACCA TCCTTACCAA 
               
               
                   
               
               
                 CTTTCAGAAT TTGGAAATGG CTCAGAAGCA GATCAATGAC TTTATCAGTC 
               
               
                   
               
               
                 AAAAAACCCATGGGAAAATT AACAACCTGA TCGAGAATAT AGACCCCGGC 
               
               
                   
               
               
                 ACTGTGATGC TTCTTGCAAATTATATTTTC TTTCGAGCCA GGTGGAAACA 
               
               
                   
               
               
                 TGAGTTTGAT CCAAATGTAA CTAAAGAGGAAGATTTCTTT CTGGAGAAAA 
               
               
                   
               
               
                 ACAGTTCAGT CAAGGTGCCC ATGATGTTCC GTAGTGGCATATACCAAGTT 
               
               
                   
               
               
                 GGCTATGACG ATAAGCTCTC TTGCACCATC CTGGAAATAC CCTACCAGAA 
               
               
                   
               
               
                 AAATATCACA GCCATCTTCA TCCTTCCTGA TGAGGGCAAG CTGAAGCACT 
               
               
                   
               
               
                 TGGAGAAGGGATTGCAGGTG GACACTTTCT CCAGATGGAA AACATTACTG 
               
               
                   
               
               
                 TCACGCAGGG TCGTAGACGTGTCTGTACCC AGACTCCACA TGACGGGCAC 
               
               
                   
               
               
                 CTTCGACCTG AAGAAGACTC TCTCCTACATAGGTGTCTCC AAAATCTTTG 
               
               
                   
               
               
                 AGGAACATGG TGATCTCACC AAGATCGCCC CTCATCGCAGCCTGAAAGTG 
               
               
                   
               
               
                 GGCGAGGCTG TGCACAAGGC TGAGCTGAAG ATGGATGAGA GGGGTACGGA 
               
               
                   
               
               
                 AGGGGCCGCT GGCACCGGAG CACAGACTCT GCCCATGGAG ACACCACTCG 
               
               
                   
               
               
                 TCGTCAAGATAGACAAACCC TATCTGCTGC TGATTTACAG CGAGAAAATA 
               
               
                   
               
               
                 CCTTCCGTGC TCTTCCTGGGAAAGATTGTT AACCCTATTG GAAAATAA 
               
               
                   
               
               
                 SEQ ID No. 36 
                   
               
               
                 SerpinB1 (Human) Protein 
                   
               
               
                 MEQLSSANTRFALDLFLALSENNPAGNIFISPFSISSAMAMVFLGTRGNTAAQLSK 
               
               
                   
               
               
                 TFHFNTVEEVHSRFQSLNADINKRGASYILKLANRLYGEKTYNFLPEFLVSTQKT 
               
               
                   
               
               
                 YGADLASVDFQHASEDARKTINQWVKGQTEGKIPELLASGMVDNMTKLVLVNA 
               
               
                   
               
               
                 IYFKGNWKDKFMKEATTNAPFRLNKKDRKTVKMMYQKKKFAYGYIEDLKCRV 
               
               
                   
               
               
                 LELPYQGEELSMVILLPDDIEDESTGLKKIEEQLTLEKLHEWTKPENLDFIEVNVSL 
               
               
                   
               
               
                 PRFKLEESYTLNSDLARLGVQDLFNSSKADLSGMSGARDIFISKIVHKSFVEVNEE 
               
               
                   
               
               
                 GTEAAAATAGIATFCMLMPEENFTADHPFLFFIRHNSSGSILFLGRFSSP 
               
               
                   
               
               
                 SEQ ID No. 37 
                   
               
               
                 SerpinB1 (Human) cDNA 
                   
               
               
                 ATGG AGCAGCTGAG CTCAGCAAAC ACCCGCTTCG CCTTGGACCT 
               
               
                   
               
               
                 GTTCCTGGCGTTGAGTGAGA ACAATCCGGC TGGAAACATC TTCATCTCTC 
               
               
                   
               
               
                 CCTTCAGCAT TTCATCTGCTATGGCCATGG TTTTTCTGGG GACCAGAGGT 
               
               
                   
               
               
                 AACACGGCAG CACAGCTGTC CAAGACTTTCCATTTCAACA CGGTTGAAGA 
               
               
                   
               
               
                 GGTTCATTCA AGATTCCAGA GTCTGAATGC TGATATCAACAAACGTGGAG 
               
               
                   
               
               
                 CGTCTTATAT TCTGAAACTT GCTAATAGAT TATATGGAGA GAAAACTTAC 
               
               
                   
               
               
                 AATTTCCTTC CTGAGTTCTT GGTTTCGACT CAGAAAACAT ATGGTGCTGA 
               
               
                   
               
               
                 CCTGGCCAGTGTGGATTTTC AGCATGCCTC TGAAGATGCA AGGAAGACCA 
               
               
                   
               
               
                 TAAACCAGTG GGTCAAAGGACAGACAGAAG GAAAAATTCC GGAACTGTTG 
               
               
                   
               
               
                 GCTTCGGGCA TGGTTGATAA CATGACCAAACTTGTGCTAG TAAATGCCAT 
               
               
                   
               
               
                 CTATTTCAAG GGAAACTGGA AGGATAAATT CATGAAAGAAGCCACGACGA 
               
               
                   
               
               
                 ATGCACCATT CAGATTGAAT AAGAAAGACA GAAAAACTGT GAAAATGATG 
               
               
                   
               
               
                 TATCAGAAGA AAAAATTTGC ATATGGCTAC ATCGAGGACC TTAAGTGCCG 
               
               
                   
               
               
                 TGTGCTGGAACTGCCTTACC AAGGCGAGGA GCTCAGCATG GTCATCCTGC 
               
               
                   
               
               
                 TGCCGGATGA CATTGAGGACGAGTCCACGG GCCTGAAGAA GATTGAGGAA 
               
               
                   
               
               
                 CAGTTGACTT TGGAAAAGTT GCATGAGTGGACTAAACCTG AGAATCTCGA 
               
               
                   
               
               
                 TTTCATTGAA GTTAATGTCA GCTTGCCCAG GTTCAAACTGGAAGAGAGTT 
               
               
                   
               
               
                 ACACTCTCAA CTCCGACCTC GCCCGCCTAG GTGTGCAGGA TCTCTTTAAC 
               
               
                   
               
               
                 AGTAGCAAGG CTGATCTGTC TGGCATGTCA GGAGCCAGAG ATATTTTTAT 
               
               
                   
               
               
                 ATCAAAAATTGTCCACAAGT CATTTGTGGA AGTGAATGAA GAGGGAACAG 
               
               
                   
               
               
                 AGGCGGCAGC TGCCACAGCAGGCATCGCAA CTTTCTGCAT GTTGATGCCC 
               
               
                   
               
               
                 GAAGAAAATT TCACTGCCGA CCATCCATTCCTTTTCTTTA TTCGGCATAA 
               
               
                   
               
               
                 TTCCTCAGGT AGCATCCTAT TCTTGGGGAG ATTTTCTTCCCCTTAG 
               
               
                   
               
               
                 SEQ ID No. 38 
                   
               
               
                 SerpinB6 variant 1 (Human) Protein 
                   
               
               
                 MDVLAEANGTFALNLLKTLGKDNSKNVFFSPMSMSCALAMVYMGAKGNTAAQ 
               
               
                   
               
               
                 MAQILSFNKSGGGGDIHQGFQSLLTEVNKTGTQYLLRMANRLFGEKSCDFLSSFR 
               
               
                   
               
               
                 DSCQKFYQAEMEELDFISAVEKSRKHINTWVAEKTEGKIAELLSPGSVDPLTRLV 
               
               
                   
               
               
                 LVNAVYFRGNWDEQFDKENTEERLFKVSKNEEKPVQMMFKQSTFKKTYIGEIFT 
               
               
                   
               
               
                 QILVLPYVGKELNMIIMLPDETTDLRTVEKELTYEKFVEWTRLDMMDEEEVEVSL 
               
               
                   
               
               
                 PRFKLEESYDMESVLRNLGMTDAFELGKADFSGMSQTDLSLSKVVHKSFVEVNE 
               
               
                   
               
               
                 EGTEAAAATAAIMMMRCARFVPRFCADHPFLFFIQHSKTNGILFCGRFSSP 
               
               
                   
               
               
                 SEQ ID No. 39 
                   
               
               
                 SerpinB6 variant 1 (Human) cDNA 
                   
               
               
                 ATGGATG TTCTCGCAGAAGCAAATGGC ACCTTTGCCT TAAACCTTTT 
               
               
                   
               
               
                 GAAAACGCTG GGTAAAGACA ACTCGAAGAATGTGTTTTTC TCACCCATGA 
               
               
                   
               
               
                 GCATGTCCTG TGCCCTGGCC ATGGTCTACA TGGGGGCAAAGGGAAACACC 
               
               
                   
               
               
                 GCTGCACAGA TGGCCCAGAT ACTTTCTTTC AATAAAAGTG GCGGTGGTGG 
               
               
                   
               
               
                 AGACATCCAC CAGGGCTTCC AGTCTCTTCT CACCGAAGTG AACAAGACTG 
               
               
                   
               
               
                 GCACGCAGTACTTGCTTAGG ATGGCCAACA GGCTCTTTGG GGAAAAGTCT 
               
               
                   
               
               
                 TGTGATTTCC TCTCATCTTTTAGAGATTCC TGCCAAAAAT TCTACCAAGC 
               
               
                   
               
               
                 AGAGATGGAG GAGCTTGACT TTATCAGCGCCGTAGAGAAG TCCAGAAAAC 
               
               
                   
               
               
                 ACATAAACAC CTGGGTAGCT GAAAAGACAG AAGGTAAAATTGCGGAGTTG 
               
               
                   
               
               
                 CTCTCTCCGG GCTCAGTGGA TCCATTGACA AGGCTGGTTC TGGTGAATGC 
               
               
                   
               
               
                 TGTCTATTTC AGAGGAAACT GGGATGAACA GTTTGACAAG GAGAACACCG 
               
               
                   
               
               
                 AGGAGAGACTGTTTAAAGTC AGCAAGAATG AGGAGAAACC TGTGCAAATG 
               
               
                   
               
               
                 ATGTTTAAGC AATCTACTTTTAAGAAGACC TATATAGGAG AAATATTTAC 
               
               
                   
               
               
                 CCAAATCTTG GTGCTTCCAT ATGTTGGCAAGGAACTGAAT ATGATCATCA 
               
               
                   
               
               
                 TGCTTCCGGA CGAGACCACT GACTTGAGAA CGGTGGAGAAAGAACTCACT 
               
               
                   
               
               
                 TACGAGAAGT TCGTAGAATG GACGAGGCTG GACATGATGG ATGAAGAGGA 
               
               
                   
               
               
                 GGTGGAAGTG TCCCTCCCGC GGTTTAAACT AGAGGAAAGC TACGACATGG 
               
               
                   
               
               
                 AGAGTGTCCTGCGCAACCTG GGCATGACTG ATGCCTTCGA GCTGGGCAAG 
               
               
                   
               
               
                 GCAGACTTCT CTGGAATGTCCCAGACAGAC CTGTCTCTGT CCAAGGTCGT 
               
               
                   
               
               
                 GCACAAGTCT TTTGTGGAGG TCAATGAGGAAGGCACGGAG GCTGCAGCCG 
               
               
                   
               
               
                 CCACAGCTGC CATCATGATG ATGCGGTGTG CCAGATTCGTCCCCCGCTTC 
               
               
                   
               
               
                 TGCGCCGACC ACCCCTTCCT TTTCTTCATC CAGCACAGCA AGACCAACGG 
               
               
                   
               
               
                 GATTCTCTTC TGCGGCCGCT TTTCCTCTCC GTGA 
               
               
                   
               
               
                 SEQ ID No. 40 
                   
               
               
                 SerpinB6 variant 2 (Human) Protein 
                   
               
               
                 MSAIMDVLAEANGTFALNLLKTLGKDNSKNVFFSPMSMSCALAMVYMGAKGN 
               
               
                   
               
               
                 TAAQMAQILSFNKSGGGGDIHQGFQSLLTEVNKTGTQYLLRMANRLFGEKSCDF 
               
               
                   
               
               
                 LSSFRDSCQKFYQAEMEELDFISAVEKSRKHINTWVAEKTEGKIAELLSPGSVD 
               
               
                   
               
               
                 PLTRLVLVNAVYFRGNWDEQFDKENTEERLFKVSKNEEKPVQMMFKQSTFKKT 
               
               
                   
               
               
                 YIGEIFTQILVLPYVGKELNMIIMLPDETTDLRTVEKELTYEKFVEWTRLDMMDE 
               
               
                   
               
               
                 EEVEVSLPRFKLEESYDMESVLRNLGMTDAFELGKADFSGMSQTDLSLSKVVHK 
               
               
                   
               
               
                 SFVEVNEEGTEAAAATAAIMMMRCARFVPRFCADHPFLFFIQHSKTNGILFCGRF 
               
               
                   
               
               
                 SSP 
               
               
                   
               
               
                 SEQ ID No. 41 
                   
               
               
                 SerpinB6 variant 2 (Human) cDNA 
                   
               
               
                 ATGT CTGCCATCATGGATGTTCTC GCAGAAGCAA ATGGCAC CTT 
               
               
                   
               
               
                 TGCCTTAAAC CTTTTGAAAA CGCTGGGTAAAGACAACTCG AAGAATGTGT 
               
               
                   
               
               
                 TTTTCTCACC CATGAGCATG TCCTGTGCCC TGGCCATGGTCTACATGGGG 
               
               
                   
               
               
                 GCAAAGGGAA ACACCGCTGC ACAGATGGCC CAGATACTTT CTTTCAATAA 
               
               
                   
               
               
                 AAGTGGCGGT GGTGGAGACA TCCACCAGGG CTTCCAGTCT CTTCTCACCG 
               
               
                   
               
               
                 AAGTGAACAAGACTGGCACG CAGTACTTGC TTAGGATGGC CAACAGGCTC 
               
               
                   
               
               
                 TTTGGGGAAA AGTCTTGTGATTTCCTCTCA TCTTTTAGAG ATTCCTGCCA 
               
               
                   
               
               
                 AAAATTCTAC CAAGCAGAGA TGGAGGAGCTTGACTTTATC AGCGCCGTAG 
               
               
                   
               
               
                 AGAAGTCCAG AAAACACATA AACACCTGGG TAGCTGAAAAGACAGAAGGT 
               
               
                   
               
               
                 AAAATTGCGG AGTTGCTCTC TCCGGGCTCA GTGGATCCAT TGACAAGGCT 
               
               
                   
               
               
                 GGTTCTGGTG AATGCTGTCT ATTTCAGAGG AAACTGGGAT GAACAGTTTG 
               
               
                   
               
               
                 ACAAGGAGAACACCGAGGAG AGACTGTTTA AAGTCAGCAA GAATGAGGAG 
               
               
                   
               
               
                 AAACCTGTGC AAATGATGTTTAAGCAATCT ACTTTTAAGA AGACCTATAT 
               
               
                   
               
               
                 AGGAGAAATA TTTACCCAAA TCTTGGTGCTTCCATATGTT GGCAAGGAAC 
               
               
                   
               
               
                 TGAATATGAT CATCATGCTT CCGGACGAGA CCACTGACTTGAGAACGGTG 
               
               
                   
               
               
                 GAGAAAGAAC TCACTTACGA GAAGTTCGTA GAATGGACGA GGCTGGACAT 
               
               
                   
               
               
                 GATGGATGAA GAGGAGGTGG AAGTGTCCCT CCCGCGGTTT AAACTAGAGG 
               
               
                   
               
               
                 AAAGCTACGACATGGAGAGT GTCCTGCGCA ACCTGGGCAT GACTGATGCC 
               
               
                   
               
               
                 TTCGAGCTGG GCAAGGCAGACTTCTCTGGA ATGTCCCAGA CAGACCTGTC 
               
               
                   
               
               
                 TCTGTCCAAG GTCGTGCACA AGTCTTTTGTGGAGGTCAAT GAGGAAGGCA 
               
               
                   
               
               
                 CGGAGGCTGC AGCCGCCACA GCTGCCATCA TGATGATGCGGTGTGCCAGA 
               
               
                   
               
               
                 TTCGTCCCCC GCTTCTGCGC CGACCACCCC TTCCTTTTCT TCATCCAGCA 
               
               
                   
               
               
                 CAGCAAGACC AACGGGATTC TCTTCTGCGG CCGCTTTTCC TCTCCGTGA 
               
               
                   
               
               
                 SEQ ID No. 42 
                   
               
               
                 SerpinB6 variant 3 (Human) Protein 
                   
               
               
                 MGAAQSLPGHRSAIMDVLAEANGTFALNLLKTLGKDNSKNVFFSPMSMSCALA 
               
               
                   
               
               
                 MVYMGAKGNTAAQMAQILSFNKSGGGGDIHQGFQSLLTEVNKTGTQYLL 
               
               
                   
               
               
                 RMANRLFGEKSCDFLSSFRDSCQKFYQAEMEELDFISAVEKSRKHINTWVAEKTE 
               
               
                   
               
               
                 GKIAELLSPGSVDPLTRLVLVNAVYFRGNWDEQFDKENTEERLFKVSKNEEKPV 
               
               
                   
               
               
                 QMMFKQSTFKKTYIGEIFTQILVLPYVGKELNMIIMLPDETTDLRTVEKELTYEKF 
               
               
                   
               
               
                 VEWTRLDMMDEEEVEVSLPRFKLEESYDMESVLRNLGMTDAFELGKADFSGMS 
               
               
                   
               
               
                 QTDLSLSKVVHKSFVEVNEEGTEAAAATAAIMMMRCARFVPRFCADHPFLFFIQ 
               
               
                   
               
               
                 HSKTNGILFCGRFSSP 
               
               
                   
               
               
                 SEQ ID No. 43 
                   
               
               
                 SerpinB6 variant 3 (Human) cDNA 
                   
               
               
                 ATGGGGGCG GCGCAGAGCCTCCCGGGCCA CAGGTCTGCC ATCATGGATG 
               
               
                   
               
               
                 TTCTCGCAGA AGCAAATGGC ACCTTTGCCTTAAACCTTTT GAAAACGCTG 
               
               
                   
               
               
                 GGTAAAGACA ACTCGAAGAA TGTGTTTTTC TCACCCATGAGCATGTCCTG 
               
               
                   
               
               
                 TGCCCTGGCC ATGGTCTACA TGGGGGCAAA GGGAAACACC GCTGCACAGA 
               
               
                   
               
               
                 TGGCCCAGAT ACTTTCTTTC AATAAAAGTG GCGGTGGTGG AGACATCCAC 
               
               
                   
               
               
                 CAGGGCTTCCAGTCTCTTCT CACCGAAGTG AACAAGACTG GCACGCAGTA 
               
               
                   
               
               
                 CTTGCTTAGG ATGGCCAACAGGCTCTTTGG GGAAAAGTCT TGTGATTTCC 
               
               
                   
               
               
                 TCTCATCTTT TAGAGATTCC TGCCAAAAATTCTACCAAGC AGAGATGGAG 
               
               
                   
               
               
                 GAGCTTGACT TTATCAGCGC CGTAGAGAAG TCCAGAAAACACATAAACAC 
               
               
                   
               
               
                 CTGGGTAGCT GAAAAGACAG AAGGTAAAAT TGCGGAGTTG CTCTCTCCGG 
               
               
                   
               
               
                 GCTCAGTGGA TCCATTGACA AGGCTGGTTC TGGTGAATGC TGTCTATTTC 
               
               
                   
               
               
                 AGAGGAAACTGGGATGAACA GTTTGACAAG GAGAACACCG AGGAGAGACT 
               
               
                   
               
               
                 GTTTAAAGTC AGCAAGAATGAGGAGAAACC TGTGCAAATG ATGTTTAAGC 
               
               
                   
               
               
                 AATCTACTTT TAAGAAGACC TATATAGGAGAAATATTTAC CCAAATCTTG 
               
               
                   
               
               
                 GTGCTTCCAT ATGTTGGCAA GGAACTGAAT ATGATCATCATGCTTCCGGA 
               
               
                   
               
               
                 CGAGACCACT GACTTGAGAA CGGTGGAGAA AGAACTCACT TACGAGAAGT 
               
               
                   
               
               
                 TCGTAGAATG GACGAGGCTG GACATGATGG ATGAAGAGGA GGTGGAAGTG 
               
               
                   
               
               
                 TCCCTCCCGCGGTTTAAACT AGAGGAAAGC TACGACATGG AGAGTGTCCT 
               
               
                   
               
               
                 GCGCAACCTG GGCATGACTGATGCCTTCGA GCTGGGCAAG GCAGACTTCT 
               
               
                   
               
               
                 CTGGAATGTC CCAGACAGAC CTGTCTCTGTCCAAGGTCGT GCACAAGTCT 
               
               
                   
               
               
                 TTTGTGGAGG TCAATGAGGA AGGCACGGAG GCTGCAGCCGCCACAGCTGC 
               
               
                   
               
               
                 CATCATGATG ATGCGGTGTG CCAGATTCGT CCCCCGCTTC TGCGCCGACC 
               
               
                   
               
               
                 ACCCCTTCCT TTTCTTCATC CAGCACAGCA AGACCAACGG GATTCTCTTC 
               
               
                   
               
               
                 TGCGGCCGCTTTTCCTCTCC GTGA 
               
               
                   
               
               
                 SEQ ID No. 44 
                   
               
               
                 SerpinB6 variant 4 (Human) Protein 
                   
               
               
                 MSSRQRGNFNYKLAFKSAIMDVLAEANGTFALNLLKTLGKDNSKNVFFSPMSMS 
               
               
                   
               
               
                 CALAMVYMGAKGNTAAQMAQILSFNKSGGGGDIHQGFQSLLTEVNKTG 
               
               
                   
               
               
                 TQYLLRMANRLFGEKSCDFLSSFRDSCQKFYQAEMEELDFISAVEKSRKHINTWV 
               
               
                   
               
               
                 AEKTEGKIAELLSPGSVDPLTRLVLVNAVYFRGNWDEQFDKENTEERLFKVSKN 
               
               
                   
               
               
                 EEKPVQMMFKQSTFKKTYIGEIFTQILVLPYVGKELNMIIMLPDETTDLRTVEKEL 
               
               
                   
               
               
                 TYEKFVEWTRLDMMDEEEVEVSLPRFKLEESYDMESVLRNLGMTDAFELGKAD 
               
               
                   
               
               
                 FSGMSQTDLSLSKVVHKSFVEVNEEGTEAAAATAAIMMMRCARFVPRFCADHPF 
               
               
                   
               
               
                 LFFIQHSKTNGILFCGRFSSP 
               
               
                   
               
               
                 SEQ ID No. 45 
                   
               
               
                 SerpinB6 variant 4 (Human) cDNA 
                   
               
               
                 ATGTCT TCAAGGCAAA GAGGAAACTT TAACTACAAA TTGGCATTTA 
               
               
                   
               
               
                 AGTCTGCCATCATGGATGTT CTCGCAGAAG CAAATGGCAC CTTTGCCTTA 
               
               
                   
               
               
                 AACCTTTTGA AAACGCTGGGTAAAGACAAC TCGAAGAATG TGTTTTTCTC 
               
               
                   
               
               
                 ACCCATGAGC ATGTCCTGTG CCCTGGCCATGGTCTACATG GGGGCAAAGG 
               
               
                   
               
               
                 GAAACACCGC TGCACAGATG GCCCAGATAC TTTCTTTCAATAAAAGTGGC 
               
               
                   
               
               
                 GGTGGTGGAG ACATCCACCA GGGCTTCCAG TCTCTTCTCA CCGAAGTGAA 
               
               
                   
               
               
                 CAAGACTGGC ACGCAGTACT TGCTTAGGAT GGCCAACAGG CTCTTTGGGG 
               
               
                   
               
               
                 AAAAGTCTTGTGATTTCCTC TCATCTTTTA GAGATTCCTG CCAAAAATTC 
               
               
                   
               
               
                 TACCAAGCAG AGATGGAGGAGCTTGACTTT ATCAGCGCCG TAGAGAAGTC 
               
               
                   
               
               
                 CAGAAAACAC ATAAACACCT GGGTAGCTGAAAAGACAGAA GGTAAAATTG 
               
               
                   
               
               
                 CGGAGTTGCT CTCTCCGGGC TCAGTGGATC CATTGACAAGGCTGGTTCTG 
               
               
                   
               
               
                 GTGAATGCTG TCTATTTCAG AGGAAACTGG GATGAACAGT TTGACAAGGA 
               
               
                   
               
               
                 GAACACCGAG GAGAGACTGT TTAAAGTCAG CAAGAATGAG GAGAAACCTG 
               
               
                   
               
               
                 TGCAAATGATGTTTAAGCAA TCTACTTTTA AGAAGACCTA TATAGGAGAA 
               
               
                   
               
               
                 ATATTTACCC AAATCTTGGTGCTTCCATAT GTTGGCAAGG AACTGAATAT 
               
               
                   
               
               
                 GATCATCATG CTTCCGGACG AGACCACTGACTTGAGAACG GTGGAGAAAG 
               
               
                   
               
               
                 AACTCACTTA CGAGAAGTTC GTAGAATGGA CGAGGCTGGACATGATGGAT 
               
               
                   
               
               
                 GAAGAGGAGG TGGAAGTGTC CCTCCCGCGG TTTAAACTAG AGGAAAGCTA 
               
               
                   
               
               
                 CGACATGGAG AGTGTCCTGC GCAACCTGGG CATGACTGAT GCCTTCGAGC 
               
               
                   
               
               
                 TGGGCAAGGCAGACTTCTCT GGAATGTCCC AGACAGACCT GTCTCTGTCC 
               
               
                   
               
               
                 AAGGTCGTGC ACAAGTCTTTTGTGGAGGTC AATGAGGAAG GCACGGAGGC 
               
               
                   
               
               
                 TGCAGCCGCC ACAGCTGCCA TCATGATGATGCGGTGTGCC AGATTCGTCC 
               
               
                   
               
               
                 CCCGCTTCTG CGCCGACCAC CCCTTCCTTT TCTTCATCCAGCACAGCAAG 
               
               
                   
               
               
                 ACCAACGGGA TTCTCTTCTG CGGCCGCTTT TCCTCTCCGT GA 
               
               
                   
               
               
                 SEQ ID No. 46 
                   
               
               
                 SerpinB6 variant 5 (Human) Protein 
                   
               
               
                 MDVLAEANGTFALNLLKTLGKDNSKNVFFSPMSMSCALAMVYMGAKGNTAAQ 
               
               
                   
               
               
                 MAQILSFNKSGGGGDIHQGFQSLLTEVNKTGTQYLLRMANRLFGEKSCDFLSSFR 
               
               
                   
               
               
                 DSCQKFYQAEMEELDFISAVEKSRKHINTWVAEKTEGKIAELLSPGSVDPLTR 
               
               
                   
               
               
                 LVLVNAVYFRGNWDEQFDKENTEERLFKVSKNEEKPVQMMFKQSTFKKTYIGEI 
               
               
                   
               
               
                 FTQILVLPYVGKELNMIIMLPDETTDLRTVEKELTYEKFVEWTRLDMMDEEEVEV 
               
               
                   
               
               
                 SLPRFKLEESYDMESVLRNLGMTDAFELGKADFSGMSQTDLSLSKVVHKSFVEV 
               
               
                   
               
               
                 NEEGTEAAAATAAIMMMRCARFVPRFCADHPFLFFIQHSKTNGILFCGRFSSP 
               
               
                   
               
               
                 SEQ ID No. 47 
                   
               
               
                 SerpinB6 variant 5 (Human) cDNA 
                   
               
               
                 ATGGA TGTTCTCGCA GAAGCAAATG GCACCTTTGCCTTAAACCTT 
               
               
                   
               
               
                 TTGAAAACGC TGGGTAAAGA CAACTCGAAG AATGTGTTTT TCTCACCCAT 
               
               
                   
               
               
                 GAGCATGTCC TGTGCCCTGG CCATGGTCTA CATGGGGGCA AAGGGAAACA 
               
               
                   
               
               
                 CCGCTGCACAGATGGCCCAG ATACTTTCTT TCAATAAAAG TGGCGGTGGT 
               
               
                   
               
               
                 GGAGACATCC ACCAGGGCTTCCAGTCTCTT CTCACCGAAG TGAACAAGAC 
               
               
                   
               
               
                 TGGCACGCAG TACTTGCTTA GGATGGCCAACAGGCTCTTT GGGGAAAAGT 
               
               
                   
               
               
                 CTTGTGATTT CCTCTCATCT TTTAGAGATT CCTGCCAAAAATTCTACCAA 
               
               
                   
               
               
                 GCAGAGATGG AGGAGCTTGA CTTTATCAGC GCCGTAGAGA AGTCCAGAAA 
               
               
                   
               
               
                 ACACATAAAC ACCTGGGTAG CTGAAAAGAC AGAAGGTAAA ATTGCGGAGT 
               
               
                   
               
               
                 TGCTCTCTCCGGGCTCAGTG GATCCATTGA CAAGGCTGGT TCTGGTGAAT 
               
               
                   
               
               
                 GCTGTCTATT TCAGAGGAAACTGGGATGAA CAGTTTGACA AGGAGAACAC 
               
               
                   
               
               
                 CGAGGAGAGA CTGTTTAAAG TCAGCAAGAA 
               
               
                   
               
               
                 TGAGGAGAAA CCTGTGCAAA TGATGTTTAA GCAATCTACT TTTAAGAAGA 
               
               
                   
               
               
                 CCTATATAGGAGAAATATTT ACCCAAATCT TGGTGCTTCC ATATGTTGGC 
               
               
                   
               
               
                 AAGGAACTGA ATATGATCATCATGCTTCCG GACGAGACCA CTGACTTGAG 
               
               
                   
               
               
                 AACGGTGGAG AAAGAACTCA CTTACGAGAAGTTCGTAGAA TGGACGAGGC 
               
               
                   
               
               
                 TGGACATGAT GGATGAAGAG GAGGTGGAAG TGTCCCTCCCGCGGTTTAAA 
               
               
                   
               
               
                 CTAGAGGAAA GCTACGACAT GGAGAGTGTC CTGCGCAACC TGGGCATGAC 
               
               
                   
               
               
                 TGATGCCTTC GAGCTGGGCA AGGCAGACTT CTCTGGAATG TCCCAGACAG 
               
               
                   
               
               
                 ACCTGTCTCTGTCCAAGGTC GTGCACAAGT CTTTTGTGGA GGTCAATGAG 
               
               
                   
               
               
                 GAAGGCACGG AGGCTGCAGCCGCCACAGCT GCCATCATGA TGATGCGGTG 
               
               
                   
               
               
                 TGCCAGATTC GTCCCCCGCT TCTGCGCCGACCACCCCTTC CTTTTCTTCA 
               
               
                   
               
               
                 TCCAGCACAG CAAGACCAAC GGGATTCTCT TCTGCGGCCGCTTTTCCTCT 
               
               
                   
               
               
                 CCGTGA 
               
               
                   
               
               
                 SEQ ID No. 48 
                   
               
               
                 SerpinB6 variant 6 (Human) Protein 
                   
               
               
                 MDVLAEANGTFALNLLKTLGKDNSKNVFFSPMSMSCALAMVYMGAKGNTAAQ 
               
               
                   
               
               
                 MAQILSFNKSGGGGDIHQGFQSLLTEVNKTGTQYLLRMANRLFGEKSCDF 
               
               
                   
               
               
                 LSSFRDSCQKFYQAEMEELDFISAVEKSRKHINTWVAEKTEGKIAELLSPGSVDPL 
               
               
                   
               
               
                 TRLVLVNAVYFRGNWDEQFDKENTEERLFKVSKNEEKPVQMMFKQSTFKKTYI 
               
               
                   
               
               
                 GEIFTQILVLPYVGKELNMIIMLPDETTDLRTVEKELTYEKFVEWTRLDMMDEEE 
               
               
                   
               
               
                 VEVSLPRFKLEESYDMESVLRNLGMTDAFELGKADFSGMSQTDLSLSKVVHKSF 
               
               
                   
               
               
                 VEVNEEGTEAAAATAAIMMMRCARFVPRFCADHPFLFFIQHSKTNGILFCGRFSS 
               
               
                   
               
               
                 P 
               
               
                   
               
               
                 SEQ ID No. 49 
                   
               
               
                 SerpinB6 variant 6 (Human) cDNA 
                   
               
               
                 ATG GATGTTCTCGCAGAAGCAAA TGGCACCTTT GCCTTAAACC 
               
               
                   
               
               
                 TTTTGAAAAC GCTGGGTAAA GACAACTCGAAGAATGTGTT TTTCTCACCC 
               
               
                   
               
               
                 ATGAGCATGT CCTGTGCCCT GGCCATGGTC TACATGGGGGCAAAGGGAAA 
               
               
                   
               
               
                 CACCGCTGCA CAGATGGCCC AGATACTTTC TTTCAATAAA AGTGGCGGTG 
               
               
                   
               
               
                 GTGGAGACAT CCACCAGGGC TTCCAGTCTC TTCTCACCGA AGTGAACAAG 
               
               
                   
               
               
                 ACTGGCACGCAGTACTTGCT TAGGATGGCC AACAGGCTCT TTGGGGAAAA 
               
               
                   
               
               
                 GTCTTGTGAT TTCCTCTCATCTTTTAGAGA TTCCTGCCAA AAATTCTACC 
               
               
                   
               
               
                 AAGCAGAGAT GGAGGAGCTT GACTTTATCAGCGCCGTAGA GAAGTCCAGA 
               
               
                   
               
               
                 AAACACATAA ACACCTGGGT AGCTGAAAAG ACAGAAGGTAAAATTGCGGA 
               
               
                   
               
               
                 GTTGCTCTCT CCGGGCTCAG TGGATCCATT GACAAGGCTG GTTCTGGTGA 
               
               
                   
               
               
                 ATGCTGTCTA TTTCAGAGGA AACTGGGATG AACAGTTTGA CAAGGAGAAC 
               
               
                   
               
               
                 ACCGAGGAGAGACTGTTTAA AGTCAGCAAG AATGAGGAGA AACCTGTGCA 
               
               
                   
               
               
                 AATGATGTTT AAGCAATCTACTTTTAAGAA GACCTATATA GGAGAAATAT 
               
               
                   
               
               
                 TTACCCAAAT CTTGGTGCTT CCATATGTTGGCAAGGAACT GAATATGATC 
               
               
                   
               
               
                 ATCATGCTTC CGGACGAGAC CACTGACTTG AGAACGGTGGAGAAAGAACT 
               
               
                   
               
               
                 CACTTACGAG AAGTTCGTAG AATGGACGAG GCTGGACATG ATGGATGAAG 
               
               
                   
               
               
                 AGGAGGTGGA AGTGTCCCTC CCGCGGTTTA AACTAGAGGA AAGCTACGAC 
               
               
                   
               
               
                 ATGGAGAGTGTCCTGCGCAA CCTGGGCATG ACTGATGCCT TCGAGCTGGG 
               
               
                   
               
               
                 CAAGGCAGAC TTCTCTGGAATGTCCCAGAC AGACCTGTCT CTGTCCAAGG 
               
               
                   
               
               
                 TCGTGCACAA GTCTTTTGTG GAGGTCAATGAGGAAGGCAC GGAGGCTGCA 
               
               
                   
               
               
                 GCCGCCACAG CTGCCATCAT GATGATGCGG TGTGCCAGATTCGTCCCCCG 
               
               
                   
               
               
                 CTTCTGCGCC GACCACCCCT TCCTTTTCTT CATCCAGCAC AGCAAGACCA 
               
               
                   
               
               
                 ACGGGATTCT CTTCTGCGGC CGCTTTTCCT CTCCGTGA 
               
               
                   
               
               
                 SEQ ID No. 50 
                   
               
               
                 SerpinB6 variant 7 (Human) Protein 
                   
               
               
                 MDVLAEANGTFALNLLKTLGKDNSKNVFFSPMSMSCALAMVYMGAKGNTAAQ 
               
               
                   
               
               
                 MAQILSFNKSGGGGDIHQGFQSLLTEVNKTGTQYLLRMANRLFGEKSCDF 
               
               
                   
               
               
                 LSSFRDSCQKFYQAEMEELDFISAVEKSRKHINTWVAEKTEGKIAELLSPGSVDPL 
               
               
                   
               
               
                 TRLVLVNAVYFRGNWDEQFDKENTEERLFKVSKNEEKPVQMMFKQSTFKKTYI 
               
               
                   
               
               
                 GEIFTQILVLPYVGKELNMIIMLPDETTDLRTVEKELTYEKFVEWTRLDMMDEEE 
               
               
                   
               
               
                 VEVSLPRFKLEESYDMESVLRNLGMTDAFELGKADFSGMSQTDLSLSKVVHKSF 
               
               
                   
               
               
                 VEVNEEGTEAAAATAAIMMMRCARFVPRFCADHPFLFFIQHSKTNGILFCGRFSS 
               
               
                   
               
               
                 P 
               
               
                   
               
               
                 SEQ ID No. 51 
                   
               
               
                 SerpinB6 variant 7 (Human) cDNA 
                   
               
               
                 AT GGATGTTCTC GCAGAAGCAA ATGGCACCTTTGCCTTAAAC 
               
               
                   
               
               
                 CTTTTGAAAA CGCTGGGTAA AGACAACTCG AAGAATGTGT 
               
               
                   
               
               
                 TTTTCTCACCCATGAGCATG TCCTGTGCCC TGGCCATGGT CTACATGGGG 
               
               
                   
               
               
                 GCAAAGGGAA ACACCGCTGCACAGATGGCC CAGATACTTT CTTTCAATAA 
               
               
                   
               
               
                 AAGTGGCGGT GGTGGAGACA TCCACCAGGGCTTCCAGTCT CTTCTCACCG 
               
               
                   
               
               
                 AAGTGAACAA GACTGGCACG CAGTACTTGC TTAGGATGGCCAACAGGCTC 
               
               
                   
               
               
                 TTTGGGGAAA AGTCTTGTGA TTTCCTCTCA TCTTTTAGAG ATTCCTGCCA 
               
               
                   
               
               
                 AAAATTCTAC CAAGCAGAGA TGGAGGAGCT TGACTTTATC AGCGCCGTAG 
               
               
                   
               
               
                 AGAAGTCCAGAAAACACATA AACACCTGGG TAGCTGAAAA GACAGAAGGT 
               
               
                   
               
               
                 AAAATTGCGG AGTTGCTCTCTCCGGGCTCA GTGGATCCAT TGACAAGGCT 
               
               
                   
               
               
                 GGTTCTGGTG AATGCTGTCT ATTTCAGAGGAAACTGGGAT GAACAGTTTG 
               
               
                   
               
               
                 ACAAGGAGAA CACCGAGGAG AGACTGTTTA AAGTCAGCAAGAATGAGGAG 
               
               
                   
               
               
                 AAACCTGTGC AAATGATGTT TAAGCAATCT ACTTTTAAGA AGACCTATAT 
               
               
                   
               
               
                 AGGAGAAATA TTTACCCAAA TCTTGGTGCT TCCATATGTT GGCAAGGAAC 
               
               
                   
               
               
                 TGAATATGATCATCATGCTT CCGGACGAGA CCACTGACTT GAGAACGGTG 
               
               
                   
               
               
                 GAGAAAGAAC TCACTTACGAGAAGTTCGTA GAATGGACGA GGCTGGACAT 
               
               
                   
               
               
                 GATGGATGAA GAGGAGGTGG AAGTGTCCCTCCCGCGGTTT AAACTAGAGG 
               
               
                   
               
               
                 AAAGCTACGA CATGGAGAGT GTCCTGCGCA ACCTGGGCATGACTGATGCC 
               
               
                   
               
               
                 TTCGAGCTGG GCAAGGCAGA CTTCTCTGGA ATGTCCCAGA CAGACCTGTC 
               
               
                   
               
               
                 TCTGTCCAAG GTCGTGCACA AGTCTTTTGT GGAGGTCAAT GAGGAAGGCA 
               
               
                   
               
               
                 CGGAGGCTGCAGCCGCCACA GCTGCCATCA TGATGATGCG GTGTGCCAGA 
               
               
                   
               
               
                 TTCGTCCCCC GCTTCTGCGCCGACCACCCC TTCCTTTTCT TCATCCAGCA 
               
               
                   
               
               
                 CAGCAAGACC AACGGGATTC TCTTCTGCGGCCGCTTTTCC TCTCCGTGA 
               
               
                   
               
               
                 SEQ ID No. 52 
                   
               
               
                 SerpinB6 variant 8 (Human) Protein 
                   
               
               
                 MDVLAEANGTFALNLLKTLGKDNSKNVFFSPMSMSCALAMVYMGAKGNTAAQ 
               
               
                   
               
               
                 MAQILSFNKSGGGGDIHQGFQSLLTEVNKTGTQYLLRMANRLFGEKSCDF 
               
               
                   
               
               
                 LSSFRDSCQKFYQAEMEELDFISAVEKSRKHINTWVAEKTEGKIAELLSPGSVDPL 
               
               
                   
               
               
                 TRLVLVNAVYFRGNWDEQFDKENTEERLFKVSKNEEKPVQMMFKQSTFKKTYI 
               
               
                   
               
               
                 GEIFTQILVLPYVGKELNMIIMLPDETTDLRTVEKELTYEKFVEWTRLDMMDEEE 
               
               
                   
               
               
                 VEVSLPRFKLEESYDMESVLRNLGMTDAFELGKADFSGMSQTDLSLSKVVHKSF 
               
               
                   
               
               
                 VEVNEEGTEAAAATAAIMMMRCARFVPRFCADHPFLFFIQHSKTNGILFCGRFSS 
               
               
                   
               
               
                 P 
               
               
                   
               
               
                 SEQ ID No. 53 
                   
               
               
                 SerpinB6 variant 8 (Human) cDNA 
                   
               
               
                 ATGGAT GTTCTCGCAGAAGCAAATGG CACCTTTGCC TTAAACCTTT 
               
               
                   
               
               
                 TGAAAACGCT GGGTAAAGAC AACTCGAAGAATGTGTTTTT CTCACCCATG 
               
               
                   
               
               
                 AGCATGTCCT GTGCCCTGGC CATGGTCTAC ATGGGGGCAAAGGGAAACAC 
               
               
                   
               
               
                 CGCTGCACAG ATGGCCCAGA TACTTTCTTT CAATAAAAGT GGCGGTGGTG 
               
               
                   
               
               
                 GAGACATCCA CCAGGGCTTC CAGTCTCTTC TCACCGAAGT GAACAAGACT 
               
               
                   
               
               
                 GGCACGCAGTACTTGCTTAG GATGGCCAAC AGGCTCTTTG GGGAAAAGTC 
               
               
                   
               
               
                 TTGTGATTTC CTCTCATCTTTTAGAGATTC CTGCCAAAAA TTCTACCAAG 
               
               
                   
               
               
                 CAGAGATGGA GGAGCTTGAC TTTATCAGCGCCGTAGAGAA GTCCAGAAAA 
               
               
                   
               
               
                 CACATAAACA CCTGGGTAGC TGAAAAGACA GAAGGTAAAA 
               
               
                   
               
               
                 TTGCGGAGTT GCTCTCTCCG GGCTCAGTGG ATCCATTGAC AAGGCTGGTT 
               
               
                   
               
               
                 CTGGTGAATGCTGTCTATTT CAGAGGAAAC TGGGATGAAC AGTTTGACAA 
               
               
                   
               
               
                 GGAGAACACC GAGGAGAGACTGTTTAAAGT CAGCAAGAAT GAGGAGAAAC 
               
               
                   
               
               
                 CTGTGCAAAT GATGTTTAAG CAATCTACTTTTAAGAAGAC CTATATAGGA 
               
               
                   
               
               
                 GAAATATTTA CCCAAATCTT GGTGCTTCCA TATGTTGGCAAGGAACTGAA 
               
               
                   
               
               
                 TATGATCATC ATGCTTCCGG ACGAGACCAC TGACTTGAGA ACGGTGGAGA 
               
               
                   
               
               
                 AAGAACTCAC TTACGAGAAG TTCGTAGAAT GGACGAGGCT GGACATGATG 
               
               
                   
               
               
                 GATGAAGAGGAGGTGGAAGT GTCCCTCCCG CGGTTTAAAC TAGAGGAAAG 
               
               
                   
               
               
                 CTACGACATG GAGAGTGTCCTGCGCAACCT GGGCATGACT GATGCCTTCG 
               
               
                   
               
               
                 AGCTGGGCAA GGCAGACTTC TCTGGAATGTCCCAGACAGA CCTGTCTCTG 
               
               
                   
               
               
                 TCCAAGGTCG TGCACAAGTC TTTTGTGGAG GTCAATGAGGAAGGCACGGA 
               
               
                   
               
               
                 GGCTGCAGCC GCCACAGCTG CCATCATGAT GATGCGGTGT 
               
               
                   
               
               
                 GCCAGATTCGTCCCCCGCTT CTGCGCCGAC CACCCCTTCC TTTTCTTCAT 
               
               
                   
               
               
                 CCAGCACAGC AAGACCAACGGGATTCTCTT CTGCGGCCGC TTTTCCTCTC 
               
               
                   
               
               
                 CGTGA 
               
               
                   
               
               
                 SEQ ID No. 54 
                   
               
               
                 SerpinB9 (Human) Protein 
                   
               
               
                 METLSNASGTFAIRLLKILCQDNPSHNVFCSPVSISSALAMVLLGAKGNTATQMA 
               
               
                   
               
               
                 QALSLNTEEDIHRAFQSLLTEVNKAGTQYLLRTANRLFGEKTCQFLSTFKESCLQF 
               
               
                   
               
               
                 YHAELKELSFIRAAEESRKHINTWVSKKTEGKIEELLPGSSIDAETRLVLVNAIYFK 
               
               
                   
               
               
                 GKWNEPFDETYTREMPFKINQEEQRPVQMMYQEATFKLAHVGEVRAQLLE 
               
               
                   
               
               
                 LPYARKELSLLVLLPDDGVELSTVEKSLTFEKLTAWTKPDCMKSTEVEVLLPKFK 
               
               
                   
               
               
                 LQEDVDMESVLRHLGIVDAFQQGKADLSAMSAERDLCLSKFVHKSFVEVNEEGT 
               
               
                   
               
               
                 EAAAASSCFVVAECCMESGPRFCADHPFLFFIRHNRANSILFCGRFSSP 
               
               
                   
               
               
                 SEQ ID No. 55 
                   
               
               
                 SerpinB9 (Human) cDNA 
                   
               
               
                 ATGGAAAC TCTTTCTAAT GCAAGTGGTA CTTTTGCCAT ACGCCTTTTA 
               
               
                   
               
               
                 AAGATACTGTGTCAAGATAA CCCTTCGCAC AACGTGTTCT GTTCTCCTGT 
               
               
                   
               
               
                 GAGCATCTCC TCTGCCCTGGCCATGGTTCT CCTAGGGGCA AAGGGAAACA 
               
               
                   
               
               
                 CCGCAACCCA GATGGCCCAG GCACTGTCTTTAAACACAGA GGAAGACATT 
               
               
                   
               
               
                 CATCGGGCTT TCCAGTCGCT TCTCACTGAA GTGAACAAGGCTGGCACACA 
               
               
                   
               
               
                 GTACCTGCTG AGAACGGCCA ACAGGCTCTT TGGAGAGAAA ACTTGTCAGT 
               
               
                   
               
               
                 TCCTCTCAAC GTTTAAGGAA TCCTGTCTTC AATTCTACCA TGCTGAGCTG 
               
               
                   
               
               
                 AAGGAGCTTTCCTTTATCAG AGCTGCAGAA GAGTCCAGGA AACACATCAA 
               
               
                   
               
               
                 CACCTGGGTC TCAAAAAAGACCGAAGGTAA AATTGAAGAG TTGTTGCCGG 
               
               
                   
               
               
                 GTAGCTCAAT TGATGCAGAA ACCAGGCTGGTTCTTGTCAA TGCCATCTAC 
               
               
                   
               
               
                 TTCAAAGGAA AGTGGAATGA ACCGTTTGAC GAAACATACACAAGGGAAAT 
               
               
                   
               
               
                 GCCCTTTAAA ATAAACCAGG AGGAGCAAAG GCCAGTGCAG ATGATGTATC 
               
               
                   
               
               
                 AGGAGGCCAC GTTTAAGCTC GCCCACGTGG GCGAGGTGCG CGCGCAGCTG 
               
               
                   
               
               
                 CTGGAGCTGCCCTACGCCAG GAAGGAGCTG AGCCTGCTGG TGCTGCTGCC 
               
               
                   
               
               
                 TGACGACGGC GTGGAGCTCAGCACGGTGGA AAAAAGTCTC ACTTTTGAGA 
               
               
                   
               
               
                 AACTCACAGC CTGGACCAAG CCAGACTGTATGAAGAGTAC TGAGGTTGAA 
               
               
                   
               
               
                 GTTCTCCTTC CAAAATTTAA ACTACAAGAG GATTATGACATGGAATCTGT 
               
               
                   
               
               
                 GCTTCGGCAT TTGGGAATTG TTGATGCCTT CCAACAGGGC AAGGCTGACT 
               
               
                   
               
               
                 TGTCGGCAAT GTCAGCGGAG AGAGACCTGT GTCTGTCCAA GTTCGTGCAC 
               
               
                   
               
               
                 AAGAGTTTTGTGGAGGTGAA TGAAGAAGGC ACCGAGGCAG CGGCAGCGTC 
               
               
                   
               
               
                 GAGCTGCTTT GTAGTTGCAGAGTGCTGCAT GGAATCTGGC CCCAGGTTCT 
               
               
                   
               
               
                 GTGCTGACCA CCCTTTCCTT TTCTTCATCAGGCACAACAG AGCCAACAGC 
               
               
                   
               
               
                 ATTCTGTTCT GTGGCAGGTT CTCATCGCCA TAA 
               
               
                   
               
               
                 SEQ ID No. 56 
                   
               
               
                 Serping1 variant 1 (Human) Protein 
                   
               
               
                 MASRLTLLTLLLLLLAGDRASSNPNATSSSSQDPESLQDRGEGKVATTVISKMLF 
               
               
                   
               
               
                 VEPILEVSSLPTTNSTTNSATKITANTTDEPTTQPTTEPTTQPTIQPTQPTTQLPTDSP 
               
               
                   
               
               
                 TQPTTGSFCPGPVTLCSDLESHSTEAVLGDALVDFSLKLYHAFSAMKKVETNMA 
               
               
                   
               
               
                 FSPFSIASLLTQVLLGAGENTKTNLESILSYPKDFTCVHQALKGFTTKGVTSVSQIF 
               
               
                   
               
               
                 HSPDLAIRDTFVNASRTLYSSSPRVLSNNSDANLELINTWVAKNTNNKISRLLDSL 
               
               
                   
               
               
                 PSDTRLVLLNAIYLSAKWKTTFDPKKTRMEPFHFKNSVIKVPMMNSKKYPVAH 
               
               
                   
               
               
                 FIDQTLKAKVGQLQLSHNLSLVILVPQNLKHRLEDMEQALSPSVFKAIMEKLEMS 
               
               
                   
               
               
                 KFQPTLLTLPRIKVTTSQDMLSIMEKLEFFDFSYDLNLCGLTEDPDLQVSAMQHQ 
               
               
                   
               
               
                 TVLELTETGVEAAAASAISVARTLLVFEVQQPFLFVLWDQQHKFPVFMGRVYDP 
               
               
                   
               
               
                 RA 
               
               
                   
               
               
                 SEQ ID No. 57 
                   
               
               
                 Serping1 variant 1 (Human) cDNA 
                   
               
               
                 ATGGCCTCC AGGCTGACCC TGCTGACCCT CCTGCTGCTG CTGCTGGCTG 
               
               
                   
               
               
                 GGGATAGAGC CTCCTCAAAT CCAAATGCTA CCAGCTCCAG CTCCCAGGAT 
               
               
                   
               
               
                 CCAGAGAGTTTGCAAGACAG AGGCGAAGGG AAGGTCGCAA CAACAGTTAT 
               
               
                   
               
               
                 CTCCAAGATG CTATTCGTTGAACCCATCCT GGAGGTTTCC AGCTTGCCGA 
               
               
                   
               
               
                 CAACCAACTC AACAACCAAT TCAGCCACCAAAATAACAGC TAATACCACT 
               
               
                   
               
               
                 GATGAACCCA CCACACAACC CACCACAGAG CCCACCACCCAACCCACCAT 
               
               
                   
               
               
                 CCAACCCACC CAACCAACTA CCCAGCTCCC AACAGATTCT CCTACCCAGC 
               
               
                   
               
               
                 CCACTACTGG GTCCTTCTGC CCAGGACCTG TTACTCTCTG CTCTGACTTG 
               
               
                   
               
               
                 GAGAGTCATTCAACAGAGGC CGTGTTGGGG GATGCTTTGG TAGATTTCTC 
               
               
                   
               
               
                 CCTGAAGCTC TACCACGCCTTCTCAGCAAT GAAGAAGGTG GAGACCAACA 
               
               
                   
               
               
                 TGGCCTTTTC CCCATTCAGC ATCGCCAGCCTCCTTACCCA GGTCCTGCTC 
               
               
                   
               
               
                 GGGGCTGGGG AGAACACCAA AACAAACCTG GAGAGCATCC 
               
               
                   
               
               
                 TCTCTTACCC CAAGGACTTC ACCTGTGTCC ACCAGGCCCT GAAGGGCTTC 
               
               
                   
               
               
                 ACGACCAAAGGTGTCACCTC AGTCTCTCAG ATCTTCCACA GCCCAGACCT 
               
               
                   
               
               
                 GGCCATAAGG GACACCTTTGTGAATGCCTC TCGGACCCTG TACAGCAGCA 
               
               
                   
               
               
                 GCCCCAGAGT CCTAAGCAAC AACAGTGACGCCAACTTGGA GCTCATCAAC 
               
               
                   
               
               
                 ACCTGGGTGG CCAAGAACAC CAACAACAAG ATCAGCCGGCTGCTAGACAG 
               
               
                   
               
               
                 TCTGCCCTCC GATACCCGCC TTGTCCTCCT CAATGCTATC TACCTGAGTG 
               
               
                   
               
               
                 CCAAGTGGAA GACAACATTT GATCCCAAGA AAACCAGAAT GGAACCCTTT 
               
               
                   
               
               
                 CACTTCAAAAACTCAGTTAT AAAAGTGCCC ATGATGAATA GCAAGAAGTA 
               
               
                   
               
               
                 CCCTGTGGCC CATTTCATTGACCAAACTTT GAAAGCCAAG GTGGGGCAGC 
               
               
                   
               
               
                 TGCAGCTCTC CCACAATCTG AGTTTGGTGATCCTGGTACC CCAGAACCTG 
               
               
                   
               
               
                 AAACATCGTC TTGAAGACAT GGAACAGGCT CTCAGCCCTTCTGTTTTCAA 
               
               
                   
               
               
                 GGCCATCATG GAGAAACTGG AGATGTCCAA GTTCCAGCCC ACTCTCCTAA 
               
               
                   
               
               
                 CACTACCCCG CATCAAAGTG ACGACCAGCC AGGATATGCT CTCAATCATG 
               
               
                   
               
               
                 GAGAAATTGGAATTCTTCGA TTTTTCTTAT GACCTTAACC TGTGTGGGCT 
               
               
                   
               
               
                 GACAGAGGAC CCAGATCTTCAGGTTTCTGC GATGCAGCAC CAGACAGTGC 
               
               
                   
               
               
                 TGGAACTGAC AGAGACTGGG GTGGAGGCGGCTGCAGCCTC CGCCATCTCT 
               
               
                   
               
               
                 GTGGCCCGCA CCCTGCTGGT CTTTGAAGTG CAGCAGCCCTTCCTCTTCGT 
               
               
                   
               
               
                 GCTCTGGGAC CAGCAGCACA AGTTCCCTGT CTTCATGGGG CGAGTATATG 
               
               
                   
               
               
                 ACCCCAGGGC CTGA 
               
               
                   
               
               
                 SEQ ID No. 58 
                   
               
               
                 Serping1 variant 2 (Human) Protein 
                   
               
               
                 MASRLTLLTLLLLLLAGDRASSNPNATSSSSQDPESLQDRGEGKVATTVISKMLF 
               
               
                   
               
               
                 VEPILEVSSLPTTNSTTNSATKITANTTDEPTTQPTTEPTTQPTIQPTQPTTQLPTDSP 
               
               
                   
               
               
                 TQPTTGSFCPGPVTLCSDLESHSTEAVLGDALVDFSLKLYHAFSAMKKVETNMA 
               
               
                   
               
               
                 FSPFSIASLLTQVLLGAGENTKTNLESILSYPKDFTCVHQALKGFTTKGVTSVSQIF 
               
               
                   
               
               
                 HSPDLAIRDTFVNASRTLYSSSPRVLSNNSDANLELINTWVAKNTNNKISRLLDSL 
               
               
                   
               
               
                 PSDTRLVLLNAIYLSAKWKTTFDPKKTRMEPFHFKNSVIKVPMMNSKKYPVAH 
               
               
                   
               
               
                 FIDQTLKAKVGQLQLSHNLSLVILVPQNLKHRLEDMEQALSPSVFKAIMEKLEMS 
               
               
                   
               
               
                 KFQPTLLTLPRIKVTTSQDMLSIMEKLEFFDFSYDLNLCGLTEDPDLQVSAMQHQ 
               
               
                   
               
               
                 TVLELTETGVEAAAASAISVARTLLVFEVQQPFLFVLWDQQHKFPVFMGRVYDP 
               
               
                   
               
               
                 RA 
               
               
                   
               
               
                 SEQ ID No. 59 
                   
               
               
                 Serping1 variant 2 (Human) cDNA 
                   
               
               
                 A TGGCCTCCAG GCTGACCCTGCTGACCCTCC TGCTGCTGCT GCTGGCTGGG 
               
               
                   
               
               
                 GATAGAGCCT CCTCAAATCC AAATGCTACCAGCTCCAGCT CCCAGGATCC 
               
               
                   
               
               
                 AGAGAGTTTG CAAGACAGAG GCGAAGGGAA GGTCGCAACAACAGTTATCT 
               
               
                   
               
               
                 CCAAGATGCT ATTCGTTGAA CCCATCCTGG AGGTTTCCAG CTTGCCGACA 
               
               
                   
               
               
                 ACCAACTCAA CAACCAATTC AGCCACCAAA ATAACAGCTA ATACCACTGA 
               
               
                   
               
               
                 TGAACCCACCACACAACCCA CCACAGAGCC CACCACCCAA CCCACCATCC 
               
               
                   
               
               
                 AACCCACCCA ACCAACTACCCAGCTCCCAA CAGATTCTCC TACCCAGCCC 
               
               
                   
               
               
                 ACTACTGGGT CCTTCTGCCC AGGACCTGTTACTCTCTGCT CTGACTTGGA 
               
               
                   
               
               
                 GAGTCATTCA ACAGAGGCCG TGTTGGGGGA TGCTTTGGTAGATTTCTCCC 
               
               
                   
               
               
                 TGAAGCTCTA CCACGCCTTC TCAGCAATGA AGAAGGTGGA GACCAACATG 
               
               
                   
               
               
                 GCCTTTTCCC CATTCAGCAT CGCCAGCCTC CTTACCCAGG TCCTGCTCGG 
               
               
                   
               
               
                 GGCTGGGGAGAACACCAAAA CAAACCTGGA GAGCATCCTC TCTTACCCCA 
               
               
                   
               
               
                 AGGACTTCAC CTGTGTCCACCAGGCCCTGA AGGGCTTCAC GACCAAAGGT 
               
               
                   
               
               
                 GTCACCTCAG TCTCTCAGAT CTTCCACAGCCCAGACCTGG CCATAAGGGA 
               
               
                   
               
               
                 CACCTTTGTG AATGCCTCTC GGACCCTGTA CAGCAGCAGCCCCAGAGTCC 
               
               
                   
               
               
                 TAAGCAACAA CAGTGACGCC AACTTGGAGC TCATCAACAC CTGGGTGGCC 
               
               
                   
               
               
                 AAGAACACCA ACAACAAGAT CAGCCGGCTG CTAGACAGTC TGCCCTCCGA 
               
               
                   
               
               
                 TACCCGCCTTGTCCTCCTCA ATGCTATCTA CCTGAGTGCC AAGTGGAAGA 
               
               
                   
               
               
                 CAACATTTGA TCCCAAGAAAACCAGAATGG AACCCTTTCA CTTCAAAAAC 
               
               
                   
               
               
                 TCAGTTATAA AAGTGCCCAT GATGAATAGCAAGAAGTACC CTGTGGCCCA 
               
               
                   
               
               
                 TTTCATTGAC CAAACTTTGA AAGCCAAGGT GGGGCAGCTGCAGCTCTCCC 
               
               
                   
               
               
                 ACAATCTGAG TTTGGTGATC CTGGTACCCC AGAACCTGAA ACATCGTCTT 
               
               
                   
               
               
                 GAAGACATGG AACAGGCTCT CAGCCCTTCT GTTTTCAAGG CCATCATGGA 
               
               
                   
               
               
                 GAAACTGGAGATGTCCAAGT TCCAGCCCAC TCTCCTAACA CTACCCCGCA 
               
               
                   
               
               
                 TCAAAGTGAC GACCAGCCAGGATATGCTCT CAATCATGGA GAAATTGGAA 
               
               
                   
               
               
                 TTCTTCGATT TTTCTTATGA CCTTAACCTGTGTGGGCTGA CAGAGGACCC 
               
               
                   
               
               
                 AGATCTTCAG GTTTCTGCGA TGCAGCACCA GACAGTGCTGGAACTGACAG 
               
               
                   
               
               
                 AGACTGGGGT GGAGGCGGCT GCAGCCTCCG CCATCTCTGT GGCCCGCACC 
               
               
                   
               
               
                 CTGCTGGTCT TTGAAGTGCA GCAGCCCTTC CTCTTCGTGC TCTGGGACCA 
               
               
                   
               
               
                 GCAGCACAAGTTCCCTGTCT TCATGGGGCG AGTATATGAC CCCAGGGCCT 
               
               
                   
               
               
                 GA 
               
               
                   
               
               
                 SEQ ID No. 60 
                   
               
               
                 Serpini1 variant 1 (Human) Protein 
                   
               
               
                 MAFLGLFSLLVLQSMATGATFPEEAIADLSVNMYNRLRATGEDENILFSPLSIALA 
               
               
                   
               
               
                 MGMMELGAQGSTQKEIRHSMGYDSLKNGEEFSFLKEFSNMVTAKESQYVMKIA 
               
               
                   
               
               
                 NSLFVQNGFHVNEEFLQMMKKYFNAAVNHVDFSQNVAVANYINKWVENNTN 
               
               
                   
               
               
                 NLVKDLVSPRDFDAATYLALINAVYFKGNWKSQFRPENTRTFSFTKDDESEVQIP 
               
               
                   
               
               
                 MMYQQGEFYYGEFSDGSNEAGGIYQVLEIPYEGDEISMMLVLSRQEVPLATLEPL 
               
               
                   
               
               
                 VKAQLVEEWANSVKKQKVEVYLPRFTVEQEIDLKDVLKALGITEIFIKDANLTGL 
               
               
                   
               
               
                 SDNKEIFLSKAIHKSFLEVNEEGSEAAAVSGMIAISRMAVLYPQVIVDHPFFFLIRN 
               
               
                   
               
               
                 RRTGTILFMGRVMHPETMNTSGHDFEEL 
               
               
                   
               
               
                 SEQ ID No. 61 
                   
               
               
                 Serpini1 variant 1 (Human) cDNA 
                   
               
               
                 ATGGCTTTC CTTGGACTCT TCTCTTTGCT GGTTCTGCAA AGTATGGCTA 
               
               
                   
               
               
                 CAGGGGCCAC TTTCCCTGAG GAAGCCATTG CTGACTTGTC AGTGAATATG 
               
               
                   
               
               
                 TATAATCGTCTTAGAGCCAC TGGTGAAGAT GAAAATATTC TCTTCTCTCC 
               
               
                   
               
               
                 ATTGAGTATT GCTCTTGCAATGGGAATGAT GGAACTTGGG GCCCAAGGAT 
               
               
                   
               
               
                 CTACCCAGAA AGAAATCCGC CACTCAATGGGATATGACAG CCTAAAAAAT 
               
               
                   
               
               
                 GGTGAAGAAT TTTCTTTCTT GAAGGAGTTT TCAAACATGGTAACTGCTAA 
               
               
                   
               
               
                 AGAGAGCCAA TATGTGATGA AAATTGCCAA TTCCTTGTTT GTGCAAAATG 
               
               
                   
               
               
                 GATTTCATGT CAATGAGGAG TTTTTGCAAA TGATGAAAAA ATATTTTAAT 
               
               
                   
               
               
                 GCAGCAGTAAATCATGTGGA CTTCAGTCAA AATGTAGCCG TGGCCAACTA 
               
               
                   
               
               
                 CATCAATAAG TGGGTGGAGAATAACACAAA CAATCTGGTG AAAGATTTGG 
               
               
                   
               
               
                 TATCCCCAAG GGATTTTGAT GCTGCCACTTATCTGGCCCT CATTAATGCT 
               
               
                   
               
               
                 GTCTATTTCA AGGGGAACTG GAAGTCGCAG TTTAGGCCTGAAAATACTAG 
               
               
                   
               
               
                 AACCTTTTCT TTCACTAAAG ATGATGAAAG TGAAGTCCAA ATTCCAATGA 
               
               
                   
               
               
                 TGTATCAGCA AGGAGAATTT TATTATGGGG AATTTAGTGA TGGCTCCAAT 
               
               
                   
               
               
                 GAAGCTGGTGGTATCTACCA AGTCCTAGAA ATACCATATG AAGGAGATGA 
               
               
                   
               
               
                 AATAAGCATG ATGCTGGTGCTGTCCAGACA GGAAGTTCCT CTTGCTACTC 
               
               
                   
               
               
                 TGGAGCCATT AGTCAAAGCA CAGCTGGTTGAAGAATGGGC AAACTCTGTG 
               
               
                   
               
               
                 AAGAAGCAAA AAGTAGAAGT ATACCTGCCC AGGTTCACAGTGGAACAGGA 
               
               
                   
               
               
                 AATTGATTTA AAAGATGTTT TGAAGGCTCT TGGAATAACT GAAATTTTCA 
               
               
                   
               
               
                 TCAAAGATGC AAATTTGACA GGCCTCTCTG ATAATAAGGA GATTTTTCTT 
               
               
                   
               
               
                 TCCAAAGCAATTCACAAGTC CTTCCTAGAG GTTAATGAAG AAGGCTCAGA 
               
               
                   
               
               
                 AGCTGCTGCT GTCTCAGGAATGATTGCAAT TAGTAGGATG GCTGTGCTGT 
               
               
                   
               
               
                 ATCCTCAAGT TATTGTCGAC CATCCATTTTTCTTTCTTAT CAGAAACAGG 
               
               
                   
               
               
                 AGAACTGGTA CAATTCTATT CATGGGACGA GTCATGCATCCTGAAACAAT 
               
               
                   
               
               
                 GAACACAAGT GGACATGATT TCGAAGAACT TTAA 
               
               
                   
               
               
                 SEQ ID No. 62 
                   
               
               
                 Serpini1 variant 2 (Human) Protein 
                   
               
               
                 MAFLGLFSLLVLQSMATGATFPEEAIADLSVNMYNRLRATGEDENILFSPLSIALA 
               
               
                   
               
               
                 MGMMELGAQGSTQKEIRHSMGYDSLKNGEEFSFLKEFSNMVTAKESQYVMKIA 
               
               
                   
               
               
                 NSLFVQNGFHVNEEFLQMMKKYFNAAVNHVDFSQNVAVANYINKWVENNTN 
               
               
                   
               
               
                 NLVKDLVSPRDFDAATYLALINAVYFKGNWKSQFRPENTRTFSFTKDDESEVQIP 
               
               
                   
               
               
                 MMYQQGEFYYGEFSDGSNEAGGIYQVLEIPYEGDEISMMLVLSRQEVPLATLEPL 
               
               
                   
               
               
                 VKAQLVEEWANSVKKQKVEVYLPRFTVEQEIDLKDVLKALGITEIFIKDANLTGL 
               
               
                   
               
               
                 SDNKEIFLSKAIHKSFLEVNEEGSEAAAVSGMIAISRMAVLYPQVIVDHPFFFLIRN 
               
               
                   
               
               
                 RRTGTILFMGRVMHPETMNTSGHDFEEL 
               
               
                   
               
               
                 SEQ ID No. 63 
                   
               
               
                 Serpini1 variant 2 (Human) cDNA 
                   
               
               
                 AT GGCTTTCCTT GGACTCTTCT CTTTGCTGGT TCTGCAAAGTATGGCTACAG 
               
               
                   
               
               
                 GGGCCACTTT CCCTGAGGAA GCCATTGCTG ACTTGTCAGT GAATATGTAT 
               
               
                   
               
               
                 AATCGTCTTA GAGCCACTGG TGAAGATGAA AATATTCTCT TCTCTCCATT 
               
               
                   
               
               
                 GAGTATTGCTCTTGCAATGG GAATGATGGA ACTTGGGGCC CAAGGATCTA 
               
               
                   
               
               
                 CCCAGAAAGA AATCCGCCACTCAATGGGAT ATGACAGCCT AAAAAATGGT 
               
               
                   
               
               
                 GAAGAATTTT CTTTCTTGAA GGAGTTTTCAAACATGGTAA CTGCTAAAGA 
               
               
                   
               
               
                 GAGCCAATAT GTGATGAAAA TTGCCAATTC CTTGTTTGTGCAAAATGGAT 
               
               
                   
               
               
                 TTCATGTCAA TGAGGAGTTT TTGCAAATGA TGAAAAAATA TTTTAATGCA 
               
               
                   
               
               
                 GCAGTAAATC ATGTGGACTT CAGTCAAAAT GTAGCCGTGG CCAACTACAT 
               
               
                   
               
               
                 CAATAAGTGGGTGGAGAATA ACACAAACAA TCTGGTGAAA GATTTGGTAT 
               
               
                   
               
               
                 CCCCAAGGGA TTTTGATGCTGCCACTTATC TGGCCCTCAT TAATGCTGTC 
               
               
                   
               
               
                 TATTTCAAGG GGAACTGGAA GTCGCAGTTTAGGCCTGAAA ATACTAGAAC 
               
               
                   
               
               
                 CTTTTCTTTC ACTAAAGATG ATGAAAGTGA AGTCCAAATTCCAATGATGT 
               
               
                   
               
               
                 ATCAGCAAGG AGAATTTTAT TATGGGGAAT TTAGTGATGG CTCCAATGAA 
               
               
                   
               
               
                 GCTGGTGGTA TCTACCAAGT CCTAGAAATA CCATATGAAG GAGATGAAAT 
               
               
                   
               
               
                 AAGCATGATGCTGGTGCTGT CCAGACAGGA AGTTCCTCTT GCTACTCTGG 
               
               
                   
               
               
                 AGCCATTAGT CAAAGCACAGCTGGTTGAAG AATGGGCAAA CTCTGTGAAG 
               
               
                   
               
               
                 AAGCAAAAAG TAGAAGTATA CCTGCCCAGGTTCACAGTGG AACAGGAAAT 
               
               
                   
               
               
                 TGATTTAAAA GATGTTTTGA AGGCTCTTGG AATAACTGAAATTTTCATCA 
               
               
                   
               
               
                 AAGATGCAAA TTTGACAGGC CTCTCTGATA ATAAGGAGAT 
               
               
                   
               
               
                 TTTTCTTTCCAAAGCAATTC ACAAGTCCTT CCTAGAGGTT AATGAAGAAG 
               
               
                   
               
               
                 GCTCAGAAGC TGCTGCTGTCTCAGGAATGA TTGCAATTAG TAGGATGGCT 
               
               
                   
               
               
                 GTGCTGTATC CTCAAGTTAT TGTCGACCATCCATTTTTCT TTCTTATCAG 
               
               
                   
               
               
                 AAACAGGAGA ACTGGTACAA TTCTATTCAT GGGACGAGTCATGCATCCTG 
               
               
                   
               
               
                 AAACAATGAA CACAAGTGGA CATGATTTCG AAGAACTTTA A 
               
            
           
         
       
     
     All publications and patent documents disclosed or referred to herein are incorporated by reference in their entirety. The foregoing description has been presented only for purposes of illustration and description. This description is not intended to limit the invention to the precise form disclosed. It is intended that the scope of the invention be defined by the claims appended hereto.