Source: http://www.google.com/patents/US8105594?dq=mirroring+data+in+a+remote+data+storage+system
Timestamp: 2015-03-02 15:10:01
Document Index: 715983095

Matched Legal Cases: ['application No. 40075', 'art 2', 'arts 1', 'Application No. 2', 'Application No: 1', 'application No. 2003262458', 'art 1', 'art 4']

Patent US8105594 - Methods for amyloid removal using anti-amyloid antibodies - Google PatentsSearch Images Maps Play YouTube News Gmail Drive More »Sign inAdvanced Patent SearchPatentsMethods and related immunoglobulin peptides and fragments thereof are disclosed that enhance the cell-mediated immune response of a patient to deposits of amyloid fibrils. These methods exploit the opsonizing effect of antibodies directed toward amyloid material or its component parts....http://www.google.com/patents/US8105594?utm_source=gb-gplus-sharePatent US8105594 - Methods for amyloid removal using anti-amyloid antibodiesAdvanced Patent SearchPublication numberUS8105594 B2Publication typeGrantApplication numberUS 12/693,085Publication dateJan 31, 2012Filing dateJan 25, 2010Priority dateMay 21, 1998Also published asUS20030147882, US20100322932Publication number12693085, 693085, US 8105594 B2, US 8105594B2, US-B2-8105594, US8105594 B2, US8105594B2InventorsAlan Solomon, Rudi Hrncic, Jonathan Stuart WallOriginal AssigneeAlan Solomon, Rudi Hrncic, Jonathan Stuart WallExport CitationBiBTeX, EndNote, RefManPatent Citations (100), Non-Patent Citations (319), Classifications (10), Legal Events (2) External Links: USPTO, USPTO Assignment, EspacenetMethods for amyloid removal using anti-amyloid antibodies
Amyloidoses are generally categorized into three groups: major systemic amyloidoses, major localized amyloidoses, and miscellaneous amyloidoses. Major systemic amyloidoses include: chronic inflammatory conditions (e.g., tuberculosis, osteomyelitis, etc.); non-infectious conditions such as juvenile rheumatoid arthritis, ankylosing spondylitis and Crohn's disease, etc.; familial Mediterranean Fever, plasma cell dyscrasia (primary amyloidosis) and various familial polyneuropathies and cardiomyopathies. Major localized amyloidoses include: chronic dialysis usually for greater than 8 years, Alzheimer's disease, Down syndrome, Hereditary cerebral hemorrhage (Dutch), and non-traumatic cerebral hemorrhage of the elderly. Miscellaneous amyloidoses include: familial polyneuropathy (Iowa), familial amyloidosis (Finnish), hereditary cerebral hemorrhage (Icelandic), CJD, Medullary carcinoma of the thyroid, atrial amyloid, and diabetes mellitus (insulinomas). Other amyloidoses include those referenced in Louis W. Heck, �The Amyloid Diseases� in Cecil's Textbook of Medicine 1504-6 (W.B. Saunders & Co., Philadelphia, Pa.; 1996).
Transmissible spongiform encephalopathies which cause CJD and Gerstmann-Str�ssler-Scheinker (GSS) disease are described by B. Chesebro et al., �Transmissible Spongiform Encephalopathies: A Brief Introduction� in FIELD'S VIROLOGY 2845-49 (3rd Edition; Raven Publishers, Philadelphia, Pa.; 1996) and in D. C. Gajdusek, �Infectious amyloids: Subacute Spongiform Encephalopathies as Transmissible Cerebral Amyloidoses,� 2851-2900 in FIELDS VIROLOGY (1996). Many of these diseases are likely mediated by prions, an infectious protein. See S. B. Prusineri, �Prions� in FIELDS VIROLOGY 2901-50 (1996) and the references contained therein. The inherited forms of amyloidoses as described on Online Mendelian Inheritance in Man (OMIM) �www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?� Each of the above is incorporated herein by reference.
FIGS. 1A and 1B are reproduced photographs of a Balb/c mouse just after an injection of amyloid is made (1A) and 14 days after the injection (1B). The injection site was shaved to better illustrate the �hump� caused by the injection of the amyloid material.
The terms �peptide,� �polypeptide� or �protein� are used interchangeably herein. The term �substantial identity,� when referring to polypeptides, indicates that the polypeptide or protein in question is at least about 30% identical to an entire naturally occurring protein or a portion thereof, usually at least about 70% identical, and preferably at least about 95% identical.
As used herein, the terms �isolated,� �substantially pure� and �substantially homogenous� are used interchangeably and describe a protein that has been separated from components which naturally accompany it. A substantially purified protein will typically comprise over about 85% to 90% of a protein sample, more usually about 95%, and preferably will be over about 99% pure. Protein purity or homogeneity may be indicated by a number of means well known in the art, such a polyacrylamide gel electrophoresis of a protein sample, followed by visualizing a single polypeptide band on a polyacrylamide gel upon staining. For certain purposes high resolution will be needed and HPLC or a similar means for purification utilized.
Nucleic acids, as used herein, may be DNA or RNA. When referring to nucleic acids, the term �substantial identity� indicates that the sequences of two nucleic acids, or designated portions thereof, when optimally aligned and compared, are identical, with appropriate nucleotide insertions or deletions, in at least about 80% of the nucleotides, usually at least about 90% to 95%, and more preferably at least about 98% to 99.5% of the nucleotides.
�Substantially complementary� similarly means that one nucleic acid hybridizes selectively to, or is identical to, another nucleic acid. Typically, selective hybridization will occur when there is at least about 55% identity over a stretch of at least 14-25 nucleotides, preferably at least about 65% identity, more preferably at least about 75%, and most preferably at least about 90% identity. See M. Kanehisa Nucleic Acids Res. 12:203 (1984), which is incorporated herein by reference.
�Isolated� or �substantially pure,� when referring to nucleic acids, refer to those that have been purified away from other cellular components or other contaminants, e.g., other cellular nucleic acids or proteins, by standard techniques, including alkaline/SDS treatment, CsCl banding, column chromatography, and others well known in the art. See, F. Ausubel, et al., ed. Current Protocols in Molecular Biology, Greene Publishing and Wiley-Interscience, New York (1987), incorporated herein by reference.
A nucleic acid is �operably linked� when it is placed into a functional relationship with another nucleic acid sequence. For instance, a promoter or enhancer is operably linked to a coding sequence if it affects the transcription of the sequence. Generally, operably linked means that the nucleic acid sequences being linked are contiguous and, where necessary to join two protein coding regions, contiguous and in reading frame.
�Expression vectors,� �cloning vectors,� or �vectors� are often plasmids or other nucleic acid molecules that are able to replicate in a chosen host cell. Expression vectors may replicate autonomously, or they may replicate by being inserted into a genome of the host cell, by methods well known in the art. Vectors that replicate autonomously will have an origin of replication or autonomous replicating sequence (�ARS�) that is functional in the chosen host cell(s). Often, it is desirable for a vector to be usable in more than one host cell, e.g., in E. coli for cloning and construction, and in a mammalian cell for expression.
�Transformation� refers to the introduction of vectors containing the nucleic acids of interest directly into host cells by well-known methods. Transformation methods, which vary depending on the type of host cell, include electroporation; transfection employing calcium chloride, rubidium chloride calcium phosphate, DEAE-dextran, or other substances; microprojectile bombardment; lipofection; infection (where the vector is an infectious agent); and other methods. See generally, Sambrook et al., (1989) op. cit. Reference to cells into which the nucleic acids described above have been introduced is meant to also include the progeny of such cells.
As used herein, �immunoglobulin polypeptide� refers to molecules that are derived from native immunoglobulins (e.g., antibodies) that have specific immunoreactive activity against a particular target, e.g., against amyloid fibrils. Antibodies are typically tetramers of immunoglobulin polypeptides. As used herein, the term �antibody� also refers to a protein consisting of one or more polypeptides substantially encoded by immunoglobulin genes. Immunoglobulin genes include those coding for the light chains, which may be of the kappa or lambda types, and those coding for the heavy chains. Heavy chain types are alpha, gamma, delta, epsilon and mu. The carboxy terminal portions of immunoglobulin heavy and light chains are constant regions, while the amino terminal portions are encoded by the myriad immunoglobulin variable region genes. The variable regions of an immunoglobulin are the portions that provide antigen recognition specificity. In particular, the specificity resides in the complementarity determining regions (�CDRs�), also known as hypervariable regions, of the immunoglobulins.
The immunoglobulins may exist in a variety of fragment forms including, for example, Fv, Fab, F(ab′), F(ab′)2, ScFv and other fragments, as well as single chains (e.g., Huston, et al., Proc. Nat. Acad. Sci. U.S.A., 85:5879-5883 (1988) and Bird, et al., Science 242:423-426 (1988), which are incorporated herein by reference). (See, generally, Hood, et al., �Immunology,� Benjamin, N.Y., 2nd ed. (1984), and Hunkapiller and Hood, Nature, 323:15-16 (1986), which are incorporated herein by reference). Single-chain antibodies, in which genes for a heavy chain and a light chain are combined into a single coding sequence, may also be used. Immunoglobulin polypeptide also encompasses a truncated immunoglobulin chain, for example, a chain containing less constant region domains than in the native polypeptide. Such truncated polypeptides can be produced by standard methods such as introducing a stop codon into the gene sequence 5′ of the domain sequences to be deleted. The truncated polypeptides can then be assembled into truncated antibodies. Antibodies as used herein also include bispecific antibodies which can be produced such as by the methods described in the following references: Glennie et al., J. Immunol., 139:2367-2375 (1987); Segal et al., Biologic Therapy of Cancer Therapy of Cancer Updates 2(4):1-12 (1992); and Shalaby et al., J. Exp. Med. 175:217-225 (1992).
�Monoclonal antibodies� may be obtained by various techniques familiar to those skilled in the art. Briefly, spleen cells from an animal immunized with a desired antigen are immortalized, commonly by fusion with a myeloma cell (see, Kohler and Milstein, Eur. J. Immunol. 6:511-519 (1976)). Alternative methods of immortalization include transformation with Epstein Barr Virus, oncogenes, or retroviruses, or other methods well known in the art. Colonies arising from single immortalized cells are screened for production of antibodies of the desired specificity and affinity for the antigen, and yield of the monoclonal antibodies produced by such cells may be enhanced by various techniques, including injection into the peritoneal cavity of a vertebrate host.
�Chimeric� antibodies are encoded by immunoglobulin genes that have been genetically engineered so that the light and heavy chain genes are composed of immunoglobulin gene segments belonging to different species. For example, the variable (V) segments of the genes from a mouse monoclonal antibody may be joined to human constant (C) segments. Such a chimeric antibody is likely to be less antigenic to a human than antibodies with mouse constant regions as well as mouse variable regions.
As used herein, the term chimeric antibody also refers to an antibody that includes an immunoglobulin that has a human-like framework and in which any constant region present has at least about 85%-90%, and preferably about 95% polypeptide sequence identity to a human immunoglobulin constant region, a so-called �humanized� immunoglobulin (see, for example, PCT Publication WO 90/07861, which is incorporated herein by reference). Hence, all parts of such a �humanized� immunoglobulin, except possibly the complementarity determining regions (CDRs), are substantially identical to corresponding parts of one or more native human immunoglobulin sequences. Where necessary, framework residues may also be replaced with those within or across species especially if certain framework residues are found to affect the structure of the CDRs. A chimeric antibody may also contain truncated variable or constant regions.
The term �framework region,� as used herein, refers to those portions of immunoglobulin light and heavy chain variable regions that are relatively conserved (i.e., other than the CDRs) among different immunoglobulins in a single species, as defined by Kabat, et al., (1987); Sequences of Proteins of Immunologic Interest, 4th Ed., U.S. Dept. Health and Human Services, which is incorporated herein by reference). As used herein, a �human-like framework region� is a framework region that in each existing chain comprises at least about 70 or more amino acid residues, typically 75 to 85 or more residues, identical to those in a human immunoglobulin.
Human constant region DNA sequences can be isolated in accordance with well-known procedures from a variety of human cells, but preferably from immortalized B-cells. The variable regions or CDRs for producing the chimeric immunoglobulins of the present invention may be similarly derived from monoclonal antibodies capable of binding to the human type amyloid, and will be produced in any convenient mammalian system, including mice, rats, rabbits, human cell lines, or other vertebrates capable of producing antibodies by well-known methods. Variable regions or CDRs may be produced synthetically, by standard recombinant methods, including polymerase chain reaction (�PER�) or through phage-display libraries. For phage display methods, see for example, McCafferty et al., Nature 348:552-554 (1990); Clackson et al., Nature 352:624-628 and Marks et al., Biotechnology 11:1145-1149 (1993). Suitable prokaryotic systems such as bacteria, yeast and phage may be employed.
Suitable source cells for the DNA sequences and host cells for immunoglobulin expression and secretion can be obtained from a number of sources, such as the American Type Culture Collection (�Catalogue of Cell Lines and Hybridomas,� Fifth edition (1985) Rockville, Md., U.S.A., which is incorporated herein by reference).
In addition to the chimeric and �humanized� immunoglobulins specifically described herein, other substantially identical modified immunoglobulins can be readily designed and manufactured utilizing various recombinant DNA techniques well known to those skilled in the art. In general, modifications of the genes may be readily accomplished by a variety of well-known techniques, such as PCR and site-directed mutagenesis (see, Gillman and Smith, Gene 8:81-97 (1979) and S. Roberts et al., Nature 328:731-734 (1987), both of which are incorporated herein by reference).
Immunoglobulin genes, in whole or in part, may also be combined with functional regions from other genes (e.g., enzymes), or with other molecules such as toxins, labels and targeting moieties to produce fusion proteins (e.g., �immunotoxins�) having novel properties. In these cases of gene fusion, the two components are present within the same polypeptide chain. Alternatively, the immunoglobulin or fragment thereof may be chemically bonded to the toxin or label by any of a variety of well-known chemical procedures. For example, when the label or cytotoxic agent is a protein and the second component is an intact immunoglobulin, the linkage may be by way of heterobifunctional cross-linkers, e.g., SPDP, carbodiimide, glutaraldehyde, or the like.
Immunotoxins, including single chain molecules, may also be produced by recombinant means. Production of various immunotoxins is well-known with the art, and methods can be found, for example in �Monoclonal Antibody-Toxin Conjugates: Aiming the Magic Bullet,� Thorpe et al., Monoclonal Antibodies in Clinical Medicine, Academic Press, pp. 168-190 (1982); E. Vitetta, Science (1987) 238:1098-1104; and G. Winter and C. Milstein, Nature (1991) 349:293-299; all incorporated herein by reference.
�Opsonize�, as used herein, refers to the binding of an immunoglobulin polypeptide to a particular target, particularly epitopes found on deposits of amyloid fibrils, such that the antibody and targets together are recognized as �foreign� by the host's cellular immune system. In other words the binding of the immunoglobulin of the present invention enhances the phagocytization of the amyloid fibrils.
�Amyloidosis�, as used herein, is intended to refer to any condition that is characterized by the presence of amyloid material. Such material may be in the form of an amyloidoma or more disperse amyloid deposits or fibrils.
The immunoglobulin polypeptides, as defined herein, are preferably anti-amyloid mAbs directed toward an amyloidoma or components or precursors thereof. The mAbs can be raised against IgLC variable region domains or, preferably, against the IgLC subsets κ1, κ4, λ8, or combinations thereof. The administration to humans of immunoglobulin polypeptides that are substantially non-human may elicit anti-antibody responses. Thus, it may be desirable to prepare anti-IgLC immunoglobulin polypeptides of the present invention which are substantially human. By �substantially human� is meant an antibody or binding fragment thereof comprised of amino acid sequences which are at least about 50% human in origin, at least 70 to 80% more preferred, and about 95-99% or more human most preferred, particularly for repeated administrations over a prolonged period as may be necessary to treat established cases of amyloidosis. As used herein, human antibody is meant to include antibodies of entirely human origin as well as those which are substantially human, unless the context indicates otherwise.
Monoclonal antibodies can also be raised against synthetic amyloid fibrils. Recombinant light chain, variable region peptides are isolated and purified in vitro using standard techniques. Synthetic fibrils are then prepared from the peptides using techniques such as those described by Wall et al., �In vitro Immunoglobulin Light Chain Fibrillogenesis,� METHODS IN ENZYMOLOGY, Vol. 309 (In Press). Antibodies are then raised against the synthetic fibrils using standard immunization techniques, typically in mice or rabbits. Monoclonal cell lines secreting anti-fibril antibodies are produced using standard hybridoma techniques.
As the generation of human anti-amyloid monoclonal antibodies may be difficult with conventional immortalization techniques, it may be desirable to first make non-human antibodies and then transfer via recombinant DNA techniques the antigen binding regions of the non-human antibodies, e.g., the Fab, complementarity determining regions (CDRs) or hypervariable regions, to human constant regions (Fc) or framework regions as appropriate to produce substantially human molecules. Such methods are generally known in the art and are described in, for example, U.S. Pat. No. 4,816,397, PCT publication WO 90/07861, and EP publications 173494 and 239400, wherein each is incorporated herein by reference. However, completely human antibodies can be produced in transgenic animals. The desired human immunoglobulin genes or gene segments can be isolated, for example by PCR from human B cells, the DNA cloned into appropriate vectors for expression in eukaryotic cells and the cloned DNA introduced into animals to produce transgenics. Animals suitable for the production of transgenics expressing human immunoglobulin include mice, rats, rabbits and pigs with rodents of transgenics that express human immunoglobulins should preferably have one or more of their endogenous immunoglobulin loci inactivated or �knocked-out� to facilitate identification and isolation of the human antibodies (See e.g., Lonberg, et al. Nature 368:856-859 (1994)).
The resulting chimeric antibodies or chimeric immunoglobulin polypeptides that bind to human amyloid are also within the scope of the present invention. A typical therapeutic chimeric antibody would be a hybrid protein consisting of the variable (V) or antigen-binding domain from a mouse immunoglobulin specific for a human amyloid antigenic determinant, and the constant (C) or effector domain from a human immunoglobulin, although domains from other mammalian species may be used for both variable and constant domains. As used herein, the therm �chimeric antibody� also refers to antibodies coded for by immunoglobulin genes in which only the CDRs are transferred from the immunoglobulin that specifically recognizes the antigenic determinants, the remainder of the immunoglobulin gene being derived from a human (or other mammalian, as desired) immunoglobulin gene. As discussed before, this type of chimeric antibody is referred to as a �humanized� (in the case of a human immunoglobulin gene being used) antibody. Also considered are recombinant human antibodies that do not contain sequences of another species.
Those skilled in the art will realize that �anti-idiotypic� antibodies can be produced by using a specific immunoglobulin as an immunogen in accordance with standard techniques. For example, infection or immunization with an amyloid fibril or fragment thereof, induces a neutralizing immunoglobulin, which has on its Fab variable region combining site an image of the amyloid that is unique to that particular immunoglobulin, i.e., an idiotype. Immunization with such an anti-amyloid immunoglobulin induces an anti-idiotype antibody, which has a conformation at its combining site that mimics the structure of the original amyloid antigen. These anti-idiotype antibodies may therefore be used instead of the amyloid antigen. See, for example, Nisonoff (1991) J. Immunol. 147:2429-2438, which is incorporated herein by reference.
Human IgLC amyloid was extracted and purified from infected organs obtained during an autopsy. The first experiments involved transplanting 50-200 mg of this amyloid material into a Balb/c mouse. The amyloid mass, or �amyloidoma,� was prepared in sterile PBS by serial sonication and grinding steps in order to produce a fine suspension of amyloid fibrils complete with the accessory molecules found in vivo. This procedure was performed to allow the amyloid to be injected into the mice through a wide-gauge hypodermic needle.
0.1 mg of one of three antibodies�κ1, κ4, or λ8, identified above�was injected into the thigh of a mouse into which amyloid had been introduced in the form of an amyloidoma as described above. The κ1 and κ4 reagents resulted in the complete removal by the host of most amyloid fibril species tested within 7 days (as little as 4 days for certain sources of amyloid). FIG. 4 shows fluoresceinated κ4 mAb binding to human amyloid.
Synthetic amyloid fibrils were prepared in vitro and used as an immunogen in mice to produce a first generation of anti-amyloid fibril mAbs. Briefly, recombinant λ6-light chain, variable region peptides were produced, isolated and purified using a bacterial expression system and standard protein purification techniques. Synthetic fibrils were prepared from these peptides by extended periods of agitation in solution as described, for example, in Wall et al., �In vitro Immunoglobulin Light Chain Fibrillogenesis,� METHODS IN ENZYMOLOGY, Vol. 309 (In Press), which is incorporated herein by reference in its entirety. Fibrils were concentrated by centrifugation at 17,000�g for 20 minutes at room temperature.
Patent CitationsCited PatentFiling datePublication dateApplicantTitleUS4666829May 15, 1985May 19, 1987University Of CaliforniaUse of antibodies and nucleotide probes in diagnosisUS4713366Dec 4, 1985Dec 15, 1987The Ohio State University Research FoundationAntigenic modification of polypeptidesUS5004697Aug 17, 1987Apr 2, 1991Univ. Of CaCationized antibodies for delivery through the blood-brain barrierUS5057540Aug 27, 1990Oct 15, 1991Cambridge Biotech CorporationSaponin adjuvantUS5187153Mar 29, 1990Feb 16, 1993Scios Nova Inc.Methods of treatment using Alzheimer's amyloid polypeptide derivativesUS5192753Apr 23, 1991Mar 9, 1993Mcgeer Patrick LAnti-rheumatoid arthritic drugs in the treatment of dementiaUS5208036Nov 16, 1990May 4, 1993Syntex (U.S.A.) Inc.Complexing a liposomal composition with a quaternary ammonium dietherUS5220013Nov 30, 1989Jun 15, 1993Scios Nova Inc.Use of materials related to amyloid protein depositsUS5231000Jul 22, 1991Jul 27, 1993The Mclean HospitalMonoclonal antibodies for Alzheimer*s diseaseUS5231170Jun 14, 1990Jul 27, 1993Paul AverbackAntiamyloidUS5270165Oct 15, 1991Dec 14, 1993The Reagents Of The University Of CaliforniaMethod of diagnosis of amyloidosesUS5387742Jun 17, 1991Feb 7, 1995Scios Nova Inc.Transgenic mice displaying the amyloid-forming pathology of alzheimer's diseaseUS5434170Dec 23, 1993Jul 18, 1995Andrulis Pharmaceuticals Corp.Administering thalidomide for treatment of Alzheiemer's diseaseUS5441870Oct 26, 1992Aug 15, 1995Athena Neurosciences, Inc.Methods for monitoring cellular processing of β-amyloid precursor proteinUS5464823Jul 26, 1993Nov 7, 1995The Regents Of The University Of CaliforniaMammalian antibiotic peptidesUS5571499Jun 6, 1995Nov 5, 1996Autoimmune, Inc.Treatment of diseases with autoimmune fragments and collagenUS5571500Jun 7, 1995Nov 5, 1996Autoimmune, Inc.Treatment of autoimmune diseases through administration by inhalation of autoantigensUS5583112Jul 2, 1992Dec 10, 1996Cambridge Biotech CorporationEnhancing immune responses in animalsUS5585100Mar 13, 1995Dec 17, 1996Henry Jackson FoundationVaccine; diagnosis, therapy and prevention of diseaseUS5593846May 9, 1995Jan 14, 1997Athena NeurosciencesMethods for the detection of soluble β-amyloid peptideUS5605811May 12, 1995Feb 25, 1997Athena Neurosciences, Inc.Methods and compositions for monitoring cellular processing of beta-amyloid precursor proteinUS5612486Nov 1, 1993Mar 18, 1997Athena Neurosciences, Inc.Transgenic animals harboring APP allele having swedish mutationUS5622701Jun 14, 1994Apr 22, 1997Protein Design Labs, Inc.Provides monoclonal antibodies that have binding site that specifically binds to p-selectin and to e-selectinUS5641473Jun 6, 1995Jun 24, 1997Autoimmune, Inc.Treatment of autoimmune diseases by aerosol administration of autoantigensUS5641474Jun 7, 1995Jun 24, 1997Autoimmune, Inc.Prevention of autoimmune diseases by aerosol administration of autoantigensUS5645820Apr 10, 1995Jul 8, 1997Autoimmune, Inc.Treatment of autoimmune diseases by aerosol administration of autoantigensUS5679348Feb 3, 1992Oct 21, 1997Cedars-Sinai Medical CenterApplying a local therapeutic or prophylactic vaccine for the eye comprising one or more recombinant hsv-1 glycoproteinsUS5688651Dec 16, 1994Nov 18, 1997Ramot University Authority For Applied Research And Development Ltd.Antiagglomerants, monoclonal antibodies, genetic engineered antibody antigens binding fragments and target polypeptides formed by denaturing target polypeptides, mixing, incubation and testingUS5721130May 12, 1995Feb 24, 1998Athena Neurosciences, Inc.Monitoring alzheimer's diseaseUS5733547Jun 2, 1995Mar 31, 1998Autoimmune, Inc.Treatment of autoimmune arthritis by oral administration of type I or type III collagenUS5736142Sep 14, 1994Apr 7, 1998Cytel CorporationAlteration of immune response using pan DR-binding peptidesUS5744368Nov 4, 1993Apr 28, 1998Research Foundation Of State University Of New YorkContacting a sample containing transthyretin with amyloid to form a complex and detecting said complexUS5750349Jan 24, 1994May 12, 1998Takeda Chemical Industries Ltd.Diagnostic composition for alzheimer's diseaseUS5750361Nov 2, 1995May 12, 1998The Regents Of The University Of CaliforniaFormation and use of prion protein (PRP) complexesUS5753624Aug 8, 1996May 19, 1998Milkhaus Laboratory, Inc.Materials and methods for treatment of plaquing diseaseUS5776468Mar 14, 1994Jul 7, 1998Smithkline Beecham Biologicals (S.A.)Vaccine compositions containing 3-0 deacylated monophosphoryl lipid AUS5780587Apr 6, 1995Jul 14, 1998President And Fellows Of Harvard CollegeCompounds and methods for inhibiting β-protein filament formation and neurotoxicityUS5786180Feb 14, 1995Jul 28, 1998Bayer CorporationAntibody specific for peptide derived from amyloid precursor proteinUS5824322Aug 20, 1996Oct 20, 1998Cytrx CorporationCompositions and methods for growth promotionUS5837473May 3, 1995Nov 17, 1998President And Fellows Of Harvard CollegeAlzheimer'sUS5837672Jun 1, 1995Nov 17, 1998Athena Neurosciences, Inc.Methods and compositions for the detection of soluble β-amyloid peptideUS5846533Sep 13, 1996Dec 8, 1998The Regents Of The University Of CaliforniaAntibodies specific for native PrPScUS5849298Aug 10, 1993Dec 15, 1998Autoimmune Inc.Treatment of multiple sclerosis by oral administration of bovine myelinUS5851996Feb 13, 1998Dec 22, 1998Milkhaus Laboratory, Inc.Materials and methods for treatment of plaquing diseasesUS5854204Mar 14, 1996Dec 29, 1998Praecis Pharmaceuticals, Inc.Aβ peptides that modulate β-amyloid aggregationUS5869054May 31, 1995Feb 9, 1999Autoimmune Inc.Treatment of multiple sclerosis by oral administration of autoantigensUS5869093Oct 24, 1994Feb 9, 1999Autoimmune Inc.Treatment of immune diseases by oral administration of autoantigensUS5877399Jun 17, 1996Mar 2, 1999Johns Hopkins UniversityTransgenic mice expressing APP-Swedish mutation develop progressive neurologic diseaseUS5935927Feb 2, 1995Aug 10, 1999The Picower Institute For Medical ResearchAlzheimer*s disease, diabetes; removal amyloid from brain, pancreasUS5955079Jun 6, 1995Sep 21, 1999Henry Jackson Foundation For The Advancement Of Military MedicineComposition comprising high molecular weight primary carrier, secondary carrier comprising t-dependent antigen conjugated to primary carrier, having enhanced antibody response to both carriersUS5955317Dec 8, 1997Sep 21, 1999Takeda Chemical Industries, Ltd.Antibodies to β-amyloids or their derivatives and use thereofUS5958883Jun 5, 1995Sep 28, 1999Board Of Regents Of The University Of Washington Office Of TechnologyFor preventing or treating alzheimer's disease, comprising administering to a subject in need thereof a peptide within an amyloid protein associated with alzheimer's diseaseUS5989566Jun 28, 1996Nov 23, 1999American Cyanamid CompanyStable vaccine compositions for parenteral administration, a method for their use, and a process for their preparationUS6057367May 7, 1997May 2, 2000Duke UniversityManipulating nitrosative stress to kill pathologic microbes, pathologic helminths and pathologically proliferating cells or to upregulate nitrosative stress defensesUS6114133Nov 14, 1994Sep 5, 2000Elan Pharmaceuticals, Inc.Detection of nervous system disorder by monitoring amino acid sequence fragments in cerebrospinal fluid and contrasting with standardUS6150091Mar 6, 1996Nov 21, 2000Baylor College Of MedicineDirect molecular diagnosis of Friedreich ataxiaUS6170226Jul 15, 1998Jan 9, 2001William ChangCapsule filling apparatusUS6262335Feb 6, 1998Jul 17, 2001Johns Hopkins UniversityTransgenic mice expressing APP mutant at amino acids 717, 721 and 722US6284221Oct 18, 1996Sep 4, 2001Elan Pharmaceuticals, Inc.Method for identifying β-amyloid peptide production inhibitorsUS6284533May 1, 1997Sep 4, 2001Avant Immunotherapeutics, Inc.Plasmid-based vaccine for treating atherosclerosisUS6294171Jan 31, 2001Sep 25, 2001Milkhaus Laboratory, Inc.Methods for treating disease states comprising administration of low levels of antibodiesUS6399314Dec 29, 1999Jun 4, 2002American Cyanamid CompanyMethods of detection of amyloidogenic proteinsUS6417178Nov 6, 1997Jul 9, 2002University Of PittsburghAmyloid binding nitrogen-linked compounds for the antemortem diagnosis of alzheimer's disease, in vivo imaging and prevention of amyloid depositsUS6743427Nov 28, 2000Jun 1, 2004Neuralab LimitedPrevention and treatment of amyloidogenic diseaseUS6750324Nov 28, 2000Jun 15, 2004Neuralab LimitedAgents and methods for treatment of diseases associated with amyloid deposits of a beta in the brain such as alzheimer's disease; entail administering agents that induce a beneficial immunogenic response against the amyloid depositUS6761888May 26, 2000Jul 13, 2004Neuralab LimitedPassive immunization treatment of Alzheimer's diseaseUS6787138Nov 28, 2000Sep 7, 2004Neuralab LimitedPrevention and treatment of amyloidogenic diseaseUS6787139Nov 28, 2000Sep 7, 2004Neuralab LimitedPrevention and treatment of amyloidogenic diseaseUS6787140Nov 28, 2000Sep 7, 2004Neuralab LimitedPrevention and treatment of amyloidogenic diseaseUS6787143Nov 28, 2000Sep 7, 2004Neuralab LimitedPrevention and treatment of amyloidogenic diseaseUS6787144Nov 28, 2000Sep 7, 2004Neuralab LimitedPrevention and treatment of amyloidogenic diseaseUS6787523Nov 30, 1998Sep 7, 2004Neuralab LimitedAlzheimer's disease, administering an a beta peptide and an adjuvant in a regime effective to induce an immune response comprising antibodies to the a beta peptide, the adjuvant enhancing the immune response to the a beta peptide,US6787637Nov 28, 2000Sep 7, 2004Neuralab LimitedComprises administering agents that induce beneficialUS6808712Mar 31, 2004Oct 26, 2004Neuralab LimitedImunogenic a beta fragment linked to immunoglobulin carrier to form conjugate; adjuvant comprising antibodies to a beta fragment enhances immune response; alzheimer*s disease treatmentUS6838592Apr 28, 2000Jan 4, 2005Nathan S. Kline Institute For Psychiatric ResearchUsing modulators of endocytic activity to treat neuodegenerative diseasesUS20010018053Jan 31, 2001Aug 30, 2001Mcmichael JohnMethods for treating disease states comprising administration of low levels of antibodiesUS20010021769Apr 9, 2001Sep 13, 2001Prusiner Stanley B.Cell culture productUS20020009445Jun 19, 2001Jan 24, 2002Yansheng DuPufification of human immunoglobulin using chromatographyUS20020077288May 22, 2001Jun 20, 2002New York UniversitySynthetic immunogenic but non-amyloidogenic peptides homologous to amyloid beta for induction of an immune response to amyloid beta and amyloid depositsUS20020086847Oct 15, 2001Jul 4, 2002Mindset Biopharmaceuticals (Usa)DNA encoding a recombinant antibody molecule end-specific for an amyloid-beta peptide for preventing or inhibiting progression of Alzheimer's DiseaseUS20020094335May 29, 2001Jul 18, 2002Robert ChalifourTreating amyloid-related disease in subject by administering antigenic amount of all-D peptide, wherein peptide elicits production of antibodies against peptide and induces an immune responseUS20020102261Nov 6, 2001Aug 1, 2002Boston Biomedical Research InstituteImmunological control of beta-amyloid levels in vivoUS20020132268Dec 19, 2001Sep 19, 2002Jui-Yoa ChangPrion isomers, methods of making, methods of using, and compositions and products comprising prion isomersUS20020133001Nov 27, 2001Sep 19, 2002Praecis Pharmaceuticals Inc.Therapeutic agents and methods of use thereof for treating an amyloidogenic diseaseUS20020136718Nov 6, 2001Sep 26, 2002Boston Biomedical Research InstituteUsing antibody which catalyzes hydrolysis of beta-amyloid at a predetermined amide linkageUS20020160394Jan 11, 2002Oct 31, 2002Bayer CorporationRegulation of transthyretin to treat obesityUS20020162129Jul 9, 2001Oct 31, 2002Lars LannfeltPrevention and treatment of alzheimer's diseaseUS20020168377Apr 5, 2002Nov 14, 2002Hermann SchaetzlPrion protein dimers useful for vaccinationUS20020187157Feb 20, 2001Dec 12, 2002Jensen Martin RolandAdministering an amyloidogenic polypeptide or subsequence thereof to induces production of antibodies against the amyloidogenic polypeptide; treatment of Alzheimer's diseaseUS20020197258Jun 24, 2002Dec 26, 2002Ghanbari Hossein A.Compositions and methods for preventing protein aggregation in neurodegenerative diseasesUS20030068325May 25, 2001Apr 10, 2003Wang Chang YiA peptide immunogen of about 20 to 100 amino acids long comprising: a helper T cell (Th) epitope, an N-terminal fragment of A beta 1-42 peptide, consisting from 10-28 amino acid residuesUS20030073655Feb 28, 2002Apr 17, 2003Chain Daniel G.Alzheimer's diseaseUS20030147882May 21, 1999Aug 7, 2003Alan SolomonAdministering to the patient an effective dose of an immunoglobulin polypeptide or fragment which binds to an amyloid fibril, thus enhance cellular immune response of a patient to remove diseased amyloid fibril depositUS20030165496Dec 6, 2001Sep 4, 2003Elan Pharmaceuticals, Inc.Alzheimer's diseaseUS20040071816Dec 10, 2002Apr 15, 2004Robert RickValve pin cross over nozzleUS20040081657May 2, 2003Apr 29, 2004Neuralab LimitedPrevention and treatment of amyloidogenic diseaseUS20040087777Mar 12, 2003May 6, 2004Elan Pharmaceuticals, Inc.Humanized antibodies that recognize beta amyloid peptideUS20040136993Oct 31, 2003Jul 15, 2004Schenk Dale B.inducing an immunogenic response against alpha-SNUS20040146521Oct 31, 2003Jul 29, 2004Schenk Dale B.Prevention and treatment of synucleinopathic diseaseUS20040219146 *Apr 19, 2004Nov 4, 2004Neuralab LimitedPrevention and treatment of amyloidogenic disease* Cited by examinerNon-Patent CitationsReference1"Decision on Rejection," 3 pages, China patent appl. No. 200410063651.1, The Patent Office of the State Intellectual Property Office of the People's Republic of China (Jul. 10, 2009) with 4 page translation.2"Memo Concerning the Official Action reported in the Covering Letter," Mexican Patent Appln. No. 011348, 1 page, received from foreign patent counsel (Feb. 15, 2006) redacted.3"Memo Concerning the Official Action reported in the Covering Letter," Mexican Patent Appln. No. 011348, 1 page, received from foreign patent counsel (Jul. 27, 2010) redacted.4"Memo Concerning the Official Action reported in the Covering Letter," Mexican Patent Appln. No. 011348, 1 page, received from foreign patent counsel (Nov. 26, 2009) redacted.5"Memo Concerning the Official Action reported in the Covering Letter," Mexican Patent Appln. No. 011348, 2 pages, received from foreign patent counsel (Sep. 12, 2008) redacted.6"Notice on Office Action," 4 pages, China patent appl. No. 200410063651.1, The Patent Office of the State Intellectual Property Office of the People's Republic of China (Nov. 11, 2005) with 6 page translation.7"Official Action" 3 pages, Russia patent appl. No. 2000132207/14, Russian Patent and Trademark Agency (Jan. 8, 2003) with 2 page translation.8"The First Office Action," 4 pages, China Patent Appl. No. 99808844.7, The Patent Office of the State Intellectual Property Office of the People's Republic of China, Beijing, China (Dec. 26, 2003) with English translation.9"The Second Office Action," 4 pages, China patent appl. No. 200410063651.1, The Patent Office of the State Intellectual Property Office of the People's Republic of China (Jan. 19, 2007) with 5 page translation.10"The Third Office Action," 3 pages, China patent appl. No. 200410063651.1, The Patent Office of the State Intellectual Property Office of the People's Republic of China (Sep. 12, 2008) with 4 page translation.11Abe et al., "Production and lmmunodiagnostic Applications of Antihuman Light Chain Monoclonal Antibodies," Am. J. Clin. Pathol. 100(1):67-74 (1993).12Aguizzi, et al., Nature, vol. 389, Oct. 1997,795-798.13Akiyama, et al., GLIA, 25:324-331 (1999).14Akiyama, et al., Neurobiology of Aging, 21 (2000) 383-421.15Andersen et al., Neurology, vol. 45, Aug. 1995, 1441-1445.16Ando et al., "Down regulation of a harmful variant protein by replacement of its normal protein," Biochim. Biophys. Acta 1362:39-46 (1997).17Ballard, "Office Action Summary," 15 pages, U.S. Appl, No. 09/316,387, United States Patent and Trademark Office, Alexandria, Virginia, USA (mailed Sep. 10, 2007).18Bard, et al., Nature Medicine, vol. 6, No. 8, Aug. 2000, 916-919.19Bauer et al., Federation of European Biochemical Societies, vol. 285, No. 1, 111-114.20Bellottii et al., "Application of Monoclonal Anti-idiotypes in the Study of AL Amyloidosis: Therapeutic Implications," Ren. Fail. 15(3):365-371 (1993).21Bellottii et al., "Use of Anti-Idiotypic Monoclonal Antibody in Studying Amyloidogenic light Chains in Cells, Urine and Fibrils: Pathophysiology and Clinical Implications," Scand. J. Immunol. 36(4):607-615 (1992).22Benjamini, et al., Immunology a Short Course, Benjamini & Leskowitz Ed., Wiley-Liss, Inc., New York, NY, 49-65, 1991.23Benjamini, et al.,Immunology: a short course, Benjamin & Leskowitz Ed., Wiley-Liss, Inc., New York, NY, p. 142.24Bercovici, et al., Eur. J. Immunol. (1999),29:345-354.25Bickel et al., "Development and in Vitro Characterization of a Cationized Monoclonal Antibody against BetaA4 Protein: A Potential Probe for Alzheimer's Disease," Bioconjugate Chem. 5(2):119-125 (1994).26Bickel et al., "Site Protected, Cationized Monoclonal Antibody Against Beta Amyloid As a Potential Diagnostic Imaging Technique for Alzheimer's Disease," Society for Neuroscience, Abstracts (325.6) vol. 18, 1992, 764.27Blass, The New England Journal of Medicine, Nov. 25, 1999, 1694-1695.28Bodmer et al., Biochemical and Biophysical Research Communications, vol. 171, No. 2, Sep. 14, 1990, 890-897.29Borchelt et al., Neuron, vol. 19, Oct. 1997, 939-945.30Boris-Lawrie et al., Current Opinion in Genetics and Development, 1993, 3:102-109.31Borrow, et al., J. Mol. Biol. (1992) 225,1075-1093.32Brugge, et al., Neurology, 44, Feb. 1994, 232-238.33Bryce, "Examiner's first report on patent application No. 40075/99," 2 pages, Australia patent appl. No. 40075/99, Australia Patent Office, Woden, Australia (mailed Mar. 5, 2002).34Cameron, Molecular Biotechnology, vol. 7, 1997, 253-265.35Caputo et al., Clin. Neuropharm, vol. 15, Suppl. 1, Pt. A., 1992, 414A-415A.36CBER, U.S.F.D.A., Thimerosal in Vaccines, http://www.fda.gov/cber/vaccine/thimerosol.htm, May 28, 2002.37Chao et al., Abstract No. 513.7, Society for Neuroscience, Abstracts, vol. 19, Part 2, Nov. 1993.38Chapman, Nature, vol. 408, 21/28 Dec. 2000, 915-916.39Check, Nature, vol. 422, Mar. 27, 2003, 370-372.40Chem. Abstract Database, 1971 :417711.41Chen et al., Nature, vol. 408, Dec. 2000, 975-979.42Chen et al., Neuroscience Letters, 125:223-226 (1991).43Chen et al., Progress in Brain Research, vol. 117,327-334 (1998).44Chung, et al.,. The Journal of Biological Chemistry, vol. 274, No. 45, Nov. 5, 1999, 32301-32308.45Coloma et al., Pharmaceutical Research, vol. 17, No. 3, 2000, 266-274.46Conway et al., Proc. Natl. Acad. Sci., Jan. 18, 2000, vol. 97, No. 2, 571-576.47Cordell Annu. Rev. Pharmacol. Toxicol. 1994, 34: 69.48Costa et al., Scand. J. Immunol. 38,177-182,1993.49Daly IV et al., Life Sciences, 1998, vol. 63, No. 23. 2121-2131.50Deena Beasley, Alzheimer's Traced to Proteins Caused by Aging, Reuters, The New York Times, Apr. 20, 2001.51Demattos et al., "Peripheral anti-Abeta antibody alters CNS and plasma Abeta clearance and decreases brain Abeta burden in a mouse model of Alzheimer's disease," Proc. Natl. Acad. Sci. 98(15):8850-8855 (published online Jul. 3, 2001).52Demattos et al., "Peripheral anti-Aβ antibody alters CNS and plasma Aβ clearance and decreases brain Aβ burden in a mouse model of Alzheimer's disease," Proc. Natl. Acad. Sci. 98(15):8850-8855 (published online Jul. 3, 2001).53Dialog/Derwent Abstract, WPI Acc No. 1997-054436/199706.54Diomede, et al., Biochem. J. (1996) 320, 563-570.55Dodart, et al., Trends in Molecular Medicine, vol. 9, No. 3, Mar. 2003, 85-87.56Du et al., Neurology, 57, Sep. (1 of 2) 2001, 801-805.57Duff et al., Nature, vol. 373, Feb. 9, 1995, 476-477.58Dumery et al., Pathol. Biol., 2001: 49: 72-85.59Elan: News, Elan and AHP Provide an Update on the Phase 2A Clinical Trial of AN-1792, Jan. 18, 2002.60Elan: News, Elan and Syeth provide update on status of Alzheimer's collaboration, Mar. 1, 2002.61Elizan et al., Journal of Neurological Sciences, 1983, 59: 341-347.62Emch, "Office Action Summary," 12 pages, U.S. Appl. No. 09/316,387, United States Patent and Trademark Office, Alexandria, Virginia, USA (mailed Apr. 23, 2002).63Emch, "Office Action Summary," 13 pages, U.S. Appl. No. 09/316,387, United States Patent and Trademark Office, Alexandria, Virginia, USA (mailed Feb. 7, 2008).64Emch, "Office Action Summary," 17 pages, U.S. Appl. No. 09/316,387, United States Patent and Trademark Office, Alexandria, Virginia, USA (mailed Dec. 24, 2008).65Falk et al., "The Systemic Amyloidoses", The New England Journal of Medicine, vol. 337, No. 13, Sep. 25, 1997, pp. 898-908.66Felsenstein et al., Neuroscience Letters, 1993, 152: 185-189.67Felsenstein, et al., Alzheimer's and Parkinson's Diseases, 401-409, 1995.68Finch et al., Neurobiol. Aging, 1996, 17(5): 809-815.69Fisher et al., Proc. Natl. Acad. Sci. USA., vol. 88, pp. 1779-1782, Mar. 1991.70Flanders et al., Neurology, 1995, 45: 1561-1569.71Frautschy, et al., Proc. Natl. Acad. Sci USA,vol. 88, 8362-8366, Oct. 1991.72Frenkel et al., Journal of Neuroimmunology 88 (1998) 85-90.73Frenkel et al., Journal of Neuroimmunology 95 (1999) 136-142.74Frenkel et al., Journal of Neuroimmunology, 106 (2000) 23-31.75Frenkel et al., PNAS, 2000, vol. 97, No. 21, 11455-11459.76Frenkel et al., Vaccine, 19 (2001), 2615-2619.77Friedland et al., Annals New York Academy of Sciences, 1997, 242-247.78Friedland et al., Molecular Neurobiology, vol. 9, 1994, 107-113.79Furlan et al., Brain (2003), 126, 285-291.80Gallo et al., "Potential Role of Apolipoprotein-E in Fibrillogenesis," Am. J. Pathol. 145(3):526-530 (1994).81Games et al., Letters to Nature, vol. 373-Feb. 9, 1995, 523-527.82Games et al., Letters to Nature, vol. 373�Feb. 9, 1995, 523-527.83Games, et al., Annals New York Academy of Sciences, 920:274-284 (2000).84Gandy et al., Tips, Mar. 1992, vol. 13, pp. 108-113.85Gardella et al., Biochemical and Biophysical Research Communications, vol. 173, No. 3, 1990, 1292-1298.86Gaskin et al., J. Exp. Med. vol. 177, Apr. 1993, 1181-1186.87Gearing et al., Annals of Neurology, vol. 39, No. 3, 1996, pp. 395-399.88Geddes et al., Neurobiology of Aging, 20 (1999) 75-79.89Gillmore and Hawkins, "Drug Insight: emerging therapies for amyloidosis," Nature Clin. Practice 2(5):263-270 (2006).90Girvan, "Examination Report," 2 pages, New Zealand patent appl. No. 507727, Intellectual Property Office of New Zealand (Apr. 22, 2002).91Giulian et al., The Journal of Biological Chemistry, vol. 273, No. 45, Nov. 6, 1998, 29719-29726.92Glenn et al., Nature, vol. 391, Feb. 26, 1998, pp. 851.93Glenner et al., Biochemical and Biophysical Research Communications, vol. 120, No. 3, May 16, 1984, pp. 885-890.94Glenner et al., Biochemical and Biophysical Research Communications, vol. 122, No. 3, Aug. 16, 1984, pp. 1131-1135.95Goate et al., Nature, vol. 349, Feb. 21, 1991, 704-706.96Goldfarb et al., Annu. Rev. Med. 1993, 46:57-65.97Goldsteins et al., Proc. Natl. Acad. Sci. USA, vol. 96 3108-3113, Mar. 1999.98Gonzalez-Fernandez et al., Immunology, 1998, 93, 149-153.99Gortner, et al., Outlines of Biochemistry, Third Edition, 322-323, John Wiley & Sons, Inc. New York, 1999.100Gozes et al., Proc. Natl. Acad. Sci. USA, vol. 93, pp. 427-432, Jan. 1996.101Gravina, et al., The American Society for Biochemistry and Molecular Biology, Inc., vol. 270, No. 13, Mar. 31, 1995, 7013-7016.102Grubeck-Loebenstein et al., "Immunization with beta-amyloid: could T-cell activation have a harmful effect?" TINS, vol. 23, No. 3, 2000, pp. 11.103Grubeck-Loebenstein et al., "Immunization with β-amyloid: could T-cell activation have a harmful effect?" TINS, vol. 23, No. 3, 2000, pp. 11.104Gupta et al., Vaccine, vol. 15, 12/13, pp. 1341-1343, 1997.105Gustafsson/Els, "International Search Report," 5 pages, PCT Appl. No. PCT/US99/11200, European Patent Office, Rijswijk, The Netherlands (mailed Oct. 7, 1999).106Haass et al., Nature, vol. 359, Sep. 24, 1992, 322-325.107Hanan et al., Amyloid: Int. J. Exp. Clin. Invest. 3, 130-133 (1996).108Hanes et al., Advanced Drug Delivery Reviews, 28 (1997) 97-119.109Haqa et al., Brain Research, 601 (1993) 88-94.110Hardy, The Finnish Medical Society DUODECIM, Ann Med 28, 255-258, 1996.111Hardy, TINS, vol. 20, No. 4, 1997, 154-159.112Harigaya et al., Biochemical and Biophysical Research Communications, vol. 211, No. 3, 1995, Jun. 26, 1995, 1015-1022.113Harrington, et al., Biochem. Biophysica Acta, 1158(1993) 120-128.114Hazama, et al., Immunology, 1993, 78, 643-649.115Helmuth, Science, vol. 289, Jul. 21, 2000, 375.116Hilbich, et al., Eur. J. Biochem. 201, 61-69 (1991).117Holmgren et al., Lancet, vol. 341, May 1, 1993, pp. 1113-1116.118Honda, et al., Journal of Clinical Laboratory Analysis 12:172-178 (1998).119Hrncic et al., "Antibody-Mediated Resolution of Ligh Chain-Associated Amyloid Deposits," Am. J. Pathol. 157(4): 1239-1246 (2000).120Hsiao et al., Science, vol. 274, Oct. 4, 1996, 99-102.121Human Immunology and Cancer Program, The University of Tennessee Medical Center/Graduate School of Medicine, Knoxville, 21 pages (publication location and date unknown).122Hyman et al., The New England Journal of Medicine, vol. 33, No. 19, 1283-1284, Nov. 9, 1995.123Hyman, Down Syndrome and Alzheimer Disease, 123-142, Wiley-Liss, Inc.,1992.124Ida, et al., The Journal of Biochemical Chemistry, vol. 271, No. 37, Sep. 13, 1996, pp. 22908-22914.125Ikeda et al., Laboratory Investigation, 1987, vol. 57 No. 4, 446-449.126Itagaki et al., Journal of Neuroimmunology, 24 (1989) 173-182.127Iwatsubo, et al., Neuron, vol. 13, Jul. 1994, 45-53.128J�ger, Clinical Immunolology and Allergology, Meditsina 1:266 (1990).129Jakes, et al., Alzheimer Disease and Associated Disorders, 1995, vol. 9, No. 1, 47-51.130Jansen et al., Immunological Rev. (1982) vol. 62,185-216.131Janus, et al., Nature, vol. 408, Dec. 2000, 979-982.132Jelic et al., Acta Neuroloqica Scandinavica 2003: 107 (Suppl. 179): 83-93.133Jen, et al., Brain Research Protocols, 2 (1997) 23-30.134Joachim et al., American Journal of Pathology, vol. 138, No. 2, Feb. 1991, 373-384.135Jobling et al., Molecular Microbiology (1991) (7), 1755-1767.136Johnson-Wood et al., Proc. Natl. Acad. Sci USA, Feb. 1997, 94, 1550-1555.137Johnstone et al., Biochemical and Biophysical Research Communications 220, 710-718 (1996).138Jorbeck et al., Infection and Immunity, May 1981, 497-502.139Kalaria, Research in Immunology, 1992, 143:637-641.140Kametani et al., "A monoclonal antibody Hy20-54-16-3L to lambda light chain of human immunoglobulin reacts with amyloid in Alzheimer's disease brain," Neurosci. Lett. 117:62-67 (1990).141Katzav-Gozansky, et al., Biotechnol. Appl. Biochem., (1996) 23:227-230.142Kawabata, Nature, vol. 354, Dec. 12, 1991, 476-478.143Kida, et al., Neuroscience Letters, 193 (1995) 105-108.144Kim, et al., Neuroscience Research Communications vol. 2, No. 3, 121-130, 1988.145Kisilevsky, "Anti-Amyloid Drugs�Potential in the Treatment of Diseases Associated with Aging", Drugs & Aging, vol. 8, No. 2, Feb. 1996, pp. 75-83.146Knudsen et al., "Summons to attend oral proceedings pursuant to Rule 115(1) EPC,"6 pages, Europe Patent Appl. No. 99923260.6, European Patent Office, Munich, Germany (Sep. 14, 2007).147Knudsen, "Communication pursuant to Article 96(2) EPC,"4 pages, Europe Patent Appl. No. 99923260.6, European Patent Office, Munich, Germany (May 18, 2005).148Knudsen, "Communication pursuant to Article 96(2) EPC,"5 pages, Europe Patent Appl. No. 99923260.6, European Patent Office, Munich, Germany (May 16, 2006).149Knudsen, "Communication pursuant to Article 96(2) EPC,"5 pages, Europe Patent Appl. No. 99923260.6, European Patent Office, Munich, Germany (Sep. 14, 2007).150Knudsen, "Consultation by telephone with the applicant / representative," 1 page, Europe Patent Appl. No. 99923260.6, European Patent Office, Munich, Germany (Apr. 20, 2009).151Knudsen, "International Preliminary Examination Report," 8 pages, PCT Appl. No. PCT/US99/11200, European Patent Office, Munich, Germany (completed Jul. 11, 2000).152Knudsen, "Written Opinion," 7 pages, PCT Appl. No. PCT/US99/11200, European Patent Office, Munich, Germany (mailed Feb. 29, 2000).153Konig, et al., Annals New York Academy of Sciences, vol. 777, Jan. 1996, 344-355.154Kovacs, et al., J. Neurol (2002) 249:1567-1582.155Kowall et al., "An in vivo model for the neurodegenerative effects of beta amyloid and protection by substance P," Proc. Natl. Acad. Sci. USA. Aug. 15, 1991; 88(16):7247-7251.156Kuo et al., "Water-soluble Aβ (N-40, N-42) Oligomers in Normal and Alzheimer Disease Brains," The Journal of Biological Chemistry, vol. 271, No. 8, Feb. 23, 1996, pp. 4077-4081.157Lampert-Etchells et al., Neurodegeneration, vol. 2, pp. 111-121 (1993).158Langer, Science, vol. 249, Sep. 28, 1990, 1527-1533.159Lannfelt et al., Behavioral Brain Research, 57 (1993) 207-213.160Lansbury, Jr., Current Opinion in Chemical Biology, 1997,260-267.161Lee, "Aβ immunization: Moving Aβ peptide from brain to blood", PNAS, vol. 98, No. 16, Jul. 31, 2001, pp. 8931-8932.162Lemere et al., Abstract No. 519.6, Soc. for Neurosciences Abstracts, vol. 25, Parts 1 & 2, 29th Annual Mtg., Oct. 23-28, 1999.163Lemere et al., Annals New York Academy of Sciences, 920, 328-331 (2001).164Li et al., Biochemistry and Molecular Biology International, vol. 43, No. 3, Oct. 1997, 601-611.165Li et al., Laboratory Investigation, 1998, vol. 78, No. 4, pp. 461-469.166Liang et al., Biochemical and Biophysical Research Communications, 219, 962-967 (1996).167Lim, Official Action, 2 pages, from Korea Patent appl. No. 10-2000-7013040, Korea Patent Office (Feb. 28, 2006) with 2 page translation.168Livingston et al,, The Journal of Immunology, 1997, 1383-1392.169Lomakin et al., "Kinetic Theory of fibrillogenesis of Amyloid β-Protein," Proc. Natl. Acad. Sci. USA 94:7942-7947 (1997).170Majocha, et al., The Journal of Nuclear Medicine, vol. 33, No. 12, Dec. 1992, 2184-2189.171Mak et al., Brain Research, 667 (1994) 138-142.172Mann et al., Annals of Neurology, vol. 40, No. 2, Aug. 1996,149-156.173Mann et al., Neuroscience Letters, 196 (1995) 105-108.174Margaret M. Esiri, Trends in Pharmacological Sciences, vol. 22 No. 1, Jan. 2001, 2-3.175Masliah et al., PNAS, Oct. 9, 2001, vol. 98, No. 21, 12245-12250.176Masters et al., Proc. Natl. Acad. Sci USA, vol. 82, Jun. 1985, 4245-4249.177Mattson, Physological Reviews, vol. 77, No. 4, Oct. 1997, 1081-1132.178McGee et al., J. Microencapsulation, 1997. vol. 14, No. 2, 197-210.179McGeer et al., Journal of Neuroscience Research, 31: 428-442 (1992).180McNeal et al., Virology, 243, 158-166 (1998).181Meda et al., Nature, vol. 374, Apr. 13, 1995, 647-650.182Meduzzi et al., Advances in Clinical Pathology, 2004, 4, 77-85.183Mena et al., Acta Neuropathol (1995) 89:50-56.184Mihara, Official Action, 5 pages, from Japan Patent appl. No. 2000-549642, Japan Patent Office (Apr. 21, 2009) with 4 page translation.185Miller et al., J. Exp. Med., vol. 174, Oct. 1991, 791-798.186Mizuno et al., Biochemica et Biophysica Acta, 1373 (1998) 119-130.187Moll et al., Journal of Neurology, Neurosurgery, and Psychiatry, 1993; 56:112-115.188Monsonego et al., PNAS, Aug. 28, 2001, vol. 98, No. 18, 10273-10278.189Morgan et al., Nature, vol. 408, Dec. 2000, 983-985.190Mori et al., The Journal of Biological Chemistry, vol. 267, No. 24, Aug. 25, 1992, 17082-17086.191Morris et al., Neurology, Sep. 1969, 39, 1159-1165.192Munch et al., J. Neural. Transm. (2002) 109: 1081-1087.193Munson, Principles of Pharmacology�Basic Concepts & Clinical Applications, Chapman & Hall, 1995, pp. 47-48.194Murphy et al., American Journal of Pathology, vol. 144, No. 5, May 1994, 1082-1088.195Mutschler et al., Drug Actions�Basic Principles and Therapeutic Aspects, Scientific Publishers; 1995, pp. 7, 11, 12.196Nakamura et al., Exp. Anim. 43(5), 711-718, 1995.197Nakamura et al., Journal of Medical Primatology, 1998,27:244-252.198Nakamura et al., Neuroscience Letters, 201 (1995) 151-154.199Nathanson et al., American Journal of Epidemiology, vol. 145, No. 11, 1997, 959-969.200Neiman, Transgenic Research 7, 73-75 (1998).201Newcombe, et al., Biochemica et Biophysica Acta. 104 (1963) 480-486.202Nicoll et al., Nature Medicine, vol. 9, No. 4, Apr. 2003, 448-452.203Noguchi "Theory and Clinical Application of Chimera Antibody and Humanized Antibody," Journal of Clinical and Experimental Medicine 167: 457-462 (1993).204Office Action dated Aug. 1, 2011 for Canadian Patent Application No. 2,325,600.205Office Action dated Sep. 13, 2011 for U.S. Appl. No. 11/911,506.206Official Action, 6 pages, Russia patent appl. No. 2004107695/14, Russian Patent and Trademark Agency (Nov. 29, 2007) with 5 page translation.207Official Action, 7 pages, Russia patent appl. No. 2004107695/14, Russian Patent and Trademark Agency (Jan. 2009) with 5 page translation.208Pahla et al., J. Mol. Med (2001) 78:703-707.209Pan et al., β-Amyloid and the BBB, 2002, 609-615.210Pardridge et al., Biochemical and Biophysical Research Communications, vol. 146, No. 1, 1987, Jul. 15, 1987, 307-313.211Paresce et al., Neuron, vol. 17,553-565, Sep. 1996.212Parsons, Peptide Hormones, Jun. 1976, J. Rudinger, Characteristics of the Amino Acids As Components of a Peptide Hormone Sequencein Peptide Hormones, 1-7, edited by Parsons, JA, et al., 1976.213Paul et al., Eur. J. Immunol. 1995,25:3521-3524.214Perutz, et al., PNAS, Apr. 16, 2002, vol. 99, No. 8, 5591-5595.215Peterson, Laboratory of Animal Science, vol. 46, No. 1, Feb. 1996, 8-14.216Philippe, et al., Journal of Neuroscience Research 46:709-719 (1996).217Prieela et al., Abstract No. 120:86406t, Chemical Abstracts, ACS, vol. 120, 1994, 652.218Prusiner et al., Proc. Natl. Acad. Sci. USA, vol. 90, 10608-10612, Nov. 1993.219Quon et al., Nature, vol. 352, Jul. 18, 1991, 239-241.220Rabin, Acta Neurol Scand 1991: 84: 441-444.221Raso, "Immunotherapy of Alzheimer's Disease," Grant Application No: 1 R43 AG15746-01, 25 pages (publication date unknown).222Raso, Immunotherapy Weekly, Abstract, Apr. 2, 1998.223Rogers et al., Proc. Natl. Acad. Sci. USA., vol. 89 (1992) 1-5.224Rohr et al., "Treatment of Crohn's Disease and Ulcerative Colitis with 7S-Immunoglobulin," Lancet 1(8525):170 (1987).225Rossor et al., Annals of the New York Academy of Sciences. vol. 695, 1993, 198-202.226Saido et al., The Journal of Biological Chemistry, 69, No. 21, Issue of May 27, 1994, 15253-15257.227Saido et al., The Journal of Biological Chemistry, vol. No. 33, Nov. 25, 1993, 25239-25243.228Saito et al., Proc. Natl. Acad. Sci USA, vol. 92, Oct. 1995, 10227-10231.229Saitoh et al., Immunological Analysis of Alzheimer's Disease Using Anti-β-Protein Monoclonal Antibodies, 60 (3) 309-320 (1991).230Sasaki et al., Brain Research, 755 (1997) 193-201.231Schehr, "Therapeutic Approaches to Alzheimer's Disease," Bio/Technology, vol. 12, Feb. 1994, pp. 140-144.232Schenk et al., Arch Neurol, vol. 57, Jul. 2000, 934-936.233Schenk et al., DNA and Cell Biology, vol. 20, No. 11, 2001, 679-681.234Schenk et al., Journal of Medicinal Chemistry, vol. 38, No. 21, Oct. 13, 1995, 4141-4154.235Schenk et al., Nature, vol. 400, Jul. 8, 1999, 173-177.236Selkoe, Imaging Alzheimer's Amyloid, Nature Biotechnology, vol. 18, Aug. 2000, 823-824.237Selkoe, Journal of Neuropathology and Experiments, vol. 53, No. 5, Sep. 1994, pp. 438-447.238Selkoe, Nature, vol. 354, Dec. 12, 1991, 432-433.239Selkoe, Neuron, vol. 6, Apr. 1991, 487-498.240Selkoe, Science, vol. 275, Jan. 31, 1997, 630-631.241Selkoe, Scientific American, Nov. 1991, 68-75.242Selkoe, Trends in Cell Biology vol. 8, Nov. 1998, 447-453.243Selkoe, Trends in Neurosciences, vol. 16, No. 10, Oct. 1993, 409-414.244Sette et al., "Disclaimer, Alteration of Immune Response Using Pan Dr-Binding Peptides," Official Gazette, Jul. 29, 1999, 1 page.245Seubert et al., Nature, vol. 359, Sep. 24, 1992, 325-327.246Shalit et al., Journal of Neuroimmunology, 52 (1994) 147-152.247Shenk et al., "Immunization with amyloid-β attenuates Alzheimer-disease-like pathology in the PDAPP mouse," Nature, vol. 400, Jul. 8, 1999, pp. 173-177.248Shiosaka, Neuroscience Research, 13 (1992), 237-255.249Sigmund, Arteriorscler. Thromb. Vasc. Biol. Jun. 2000, 1425-1429.250Sigurdsson et al., Journal of Neuropathology and Experimental Neurology, vol. 59, No. 1, Jan. 2000, 11-17.251Sigurdsson et al., Neuroscience Letters 336 (2003) 185-187.252Sinha et al., Annals New York Academy of Sciences, 920:206-208 (2000).253Sipe, Ann. Rev. Biochem. 1992, 61: 947-975.254Siqurdsson et al., American Journal of Pathology, vol. 161, No. 1, Jul. 2002, 13-17.255Siqurdsson et al., Neurobiology of Aging, 23 (2002) 1001-1008.256Skolnick et al., Trends in Biotech, 18(1), 34-39, 2000.257Small et al., Nat. Rev. Neuroscience, vol. 2, (8):595-598 (2001).258Smits et al., The Veterinary Quarterly, vol. 19, No. 3, Sep. 1997, 101-105.259Solomon et al. Proc. Natl. Acad. Sci. USA, Apr. 1997, vol. 94, 4109-4112.260Solomon et al., Advances in Molecular and Cell Biology, vol. 15A, 1996, 33-45.261Solomon et al., Proc. Natl. Acad. Sci. USA, Jan. 1996, vol. 93, 452-455.262Solomon, "New Approach Towards Fast Induction of Anti β-Amyloid Peptide Immune Response," Dept. of Mol. Microbiology & Biotechnology, Tel-Aviv University, Ramat Aviv, Tel-Aviv, Israel, p. 182 (publication location and date unknown).263Solomon, "Pro-Rx (Protein Therapeutics)," "Pro-Dx, (Protein Diagnostics)," and "BioBank (Human Myeloma and Amyloid Protein, Cell, & Antibody Resource," 5 pages, University of Tennessee Medical Center (publication location and date unknown).264Solomon, et al., "Activity of Monoclonal Antibodies in Prevention of In Vitro Aggregation of Their Antigens," Immunotechnology, vol. 2, No. 4, Nov. 1996 , p. 305, Abstract.265Soto et al., Nat. Med. 4(7), 822-826, 1998.266Southwick et al., "Assessment of Amyloid β Protein in Cerebrospinal Fluid as an Aid in the Diagnosis of Alzheimer's Disease," Journal of Neurochemistry, vol. 66, No. 1, 1996, 259-265.267Spooner et al., Vaccine, 21 (2002) 290-297.268St. George-Hyslop et al., Nature, vol. 400, Jul. 8, 1999, 116-117.269Stein et al., The Journal of Neuroscience, Sep. 1, 2002, 22(17):7380-7388.270Stoute et al., The New England Journal of Medicine, Jan. 9, 1997, 86-91.271Strawman Limited, "Notice of opposition to a European patent," 40 pages, Europe Patent Appl. No. 99923260.6, European Patent Office, Munich, Germany (Jan. 21, 2011).272Sturchler-Pierrat, et al., Proc. Natl. Acad. Sci, USA, Nov. 1997�vol. 94, 13287-13292.273Su et al., Brain Research, 818(1) (1999) 105-117.274Su et al., Journal of Neuroscience Research, 53:177-186 (1998).275Suzuki et al., American Journal of Pathology, vol. 145, No. 2, Aug. 1994, 452-460.276Suzuki et al., Science, vol. 264, May 27, 1994, 1336-1340.277Szendrei et al., International Journal Peptide Protein Research, 47, 1996, 289-296.278Tal et al., Journal of Neuroscience Research 71:286-290 (2003).279Tan et al., Histopathology, 1994, 25:403-414.280Tan, Official Action, 3 pages, Canada Patent Appl. No. 2,325,600, Canada Intellectual Property Office, Gatineau, Quebec, Canada (Feb. 11, 2009).281Tan, Official Action, 5 pages, Canada Patent Appl. No. 2,325,600, Canada Intellectual Property Office, Gatineau, Quebec, Canada (Jan. 3, 2008).282Tanaka et al., European Journal of Pharmacology 352 (1998), 135-142.283Tekirian et al., Journal of Neuropathology and Experimental Neurology,vol. 57, No. 1, Jan. 1998, pp. 76-94.284Tennent et al.,. Proc. Natl. Acad. Sci. USA, vol. 92, May 1995, 4299-4303.285The Boston Globe, "Immune cells may promote Alzheimer's, a study finds," Associated Press, Apr. 17, 1994, Wednesday AM cycle.286The New York Times, "Anti-Inflammatory Drugs May Impede Alzheimer's," Feb. 20, 1994.287Thorsett et al., Current Opinion in Chemical Biology, 2000, 4:377-382.288Tillott, "Examiner's first report on patent application No. 2003262458," 3 pages, Australia patent appl. No. 2003262458, Australia Patent Office (Sep. 6, 2006).289Tjernberg et al., "Arrest of β-Amyloid Fibril Formation by a Pentapeptide Ligand", The Journal of Biological Chemistry, vol. 271, No. 15, Apr. 12, 1996, pp. 8545-8548.290Trieb et al., Immunobiology, vol. 191, No. 2-3, 1994, 114-115.291Tsuzuki et al., Neuroscience Letters 202 (1995) 77-80.292Turner, "Office Action Summary," 17 pages, U.S. Appl. No. 09/316,387, United States Patent and Trademark Office, Alexandria, Virginia, USA (mailed Sep. 30, 2003).293Turner, "Office Action Summary," 22 pages, U.S. Appl. No. 09/316,387, United States Patent and Trademark Office, Alexandria, Virginia, USA (mailed Jun. 14, 2004).294Turner, "Office Action Summary," 29 pages, U.S. Appl. No. 09/316,387, United States Patent and Trademark Office, Alexandria, Virginia, USA (mailed Jun. 20, 2005).295Turner, "Office Action Summary," 35 pages, U.S. Appl. No. 09/316,387, United States Patent and Trademark Office, Alexandria, Virginia, USA (mailed May 9, 2006).296Turner, "Office Action Summary," 9 pages, U.S. Appl. No. 09/316,387, United States Patent and Trademark Office, Alexandria, Virginia, USA (mailed Jan. 18, 2001).297Van Gool et al., Neuroscience Letters 172 (1994) 122-124.298Vehmas et al., DNA and Cell Biology, vol. 20, No. 11, 2001, 713-721.299Walker et al., "Labeling of Cerebral Amyloid in Vivo with a Monoclonal Antibody," J. Neuropath. Exp. Neurol. 53(4):377-383 (1994).300Wall et al., "In vitro immunoglobulin light chain fibrillogenesis," Meth. Enzymol. 309:204-217 (1999).301Wang, et al., The Journal of Biological Chemistry, Dec. 13, 1996, vol. 271, No. 50, pp. 31894-31902.302Weiner et al., Annals of Neurology, vol. 48, No. 4, Oct. 2000, 567-579.303Weiner et al., Annual Rev. Immunol. 1994, 809-837.304Weissmann et al., Current Opinion in Neurobiology 1997, 7:695-700.305Weldon et al., "Neurotoxicity of Aβ Peptide: Confocal Imaging of Cellular Changes Induced by β-Amyloid in Rat CNS in Vivo," Society for Neuroscience Abstracts, vol. 22, Part 1, p. 193, Abs. No. 81.6 (1996).306Wen, Journal of Food and Drug Analysis, 1998, 6(2):465-476.307Wengenack et al., Nature Biotechnology, Aug. 2000, vol. 18, 868-872.308Werbeek et al., AJP Jan. 1994, vol. 144, No. 1, 104-116.309Wisconsin Alumni Research Foundation, Final Report, Contract No. Ph 43-67-684, Jun. 19,1969, 1-130.310Wisniewski et al., Biochemical Society Transactions, (2002) vol. 30, Part 4, 574-578.311Wong et al., Proc. Natl. Acad. Sci. USA 82 (1985) 8729-8732.312Wrightham et al., Blood 69(3):919-23 (1987).313Wu et al., J. Clin. Invest. vol. 100, No. 7, Oct. 1997, 1804-1812.314Yamada et al., "Further Characterization of a Monoclonal Antibody Recognizing Apolipoprotein E Peptides in Amyloid Deposits," Annals Clin. Lab. Sci. 27(4):276-281 (1997).315Yamaguchi et al., Acta Neuropathol. (1998) 95: 217-222.316Yanagisawa et al., Neurolobiology of Aging, 1998, vol. 19, No. 15, 565-567.317Yoshigoe, Official Action, 3 pages, from Japan Patent appl. No. 2000-549642, Japan Patent Office (Nov. 24, 2009) with 3 page translation.318Younkin, Nature Medicine, vol. 7, No. 1, Jan. 2001, 18-19.319Yu et al., "Peptide-Antibody Conjugates for Tumour Therapy: A MHC-Class-II-Restricted Tetanus Toxin Peptide Coupled to an Anti-Ig Light Chain Antibody can Induce Cytotoxic Lysis of a Human B-Cell Lymphoma by Specific CD4 T Cells," Int. J. Cancer 56:244-248 (1994).Classifications U.S. Classification424/135.1, 424/152.1, 424/172.1, 424/133.1International ClassificationC07K16/18, A61K38/00, A61K39/395Cooperative ClassificationC07K16/18, A61K38/00European ClassificationC07K16/18Legal EventsDateCodeEventDescriptionApr 21, 2011ASAssignmentOwner name: UNIVERSITY OF TENNESSEE RESEARCH FOUNDATION, TENNEFree format text: CHANGE OF NAME;ASSIGNOR:THE UNIVERSITY OF TENNESSEE RESEARCH CORPORATION;REEL/FRAME:026160/0541Effective date: 20030514Apr 18, 2011ASAssignmentOwner name: THE UNIVERSITY OF TENNESSEE RESEARCH CORPORATION,Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNORS:SOLOMON, ALAN;HRNCIC, RUDI;WALL, JONATHAN STUART;SIGNINGDATES FROM 19990625 TO 19990709;REEL/FRAME:026143/0076RotateOriginal ImageGoogle Home - Sitemap - USPTO Bulk Downloads - Privacy Policy - Terms of Service - About Google Patents - Send FeedbackData provided by IFI CLAIMS Patent Services