Source: http://www.google.com/patents/US7550143?dq=6,332,126
Timestamp: 2017-07-21 19:54:12
Document Index: 369225756

Matched Legal Cases: ['§ 119', 'Application No. 60', 'Application No. 60', 'Application No. 60', 'Application No. 60', 'Application No. 60']

Patent US7550143 - Methods for generating stably linked complexes composed of homodimers ... - Google PatentsSearch Images Maps Play YouTube News Gmail Drive More »Sign inPatentsThe present invention concerns methods and compositions for stably tethered structures of defined compositions, which may have multiple functionalities and/or binding specificities. Particular embodiments concern homodimers comprising monomers that contain a dimerization and docking domain attached to...http://www.google.com/patents/US7550143?utm_source=gb-gplus-sharePatent US7550143 - Methods for generating stably linked complexes composed of homodimers, homotetramers or dimers of dimers and usesAdvanced Patent SearchTry the new Google Patents, with machine-classified Google Scholar results, and Japanese and South Korean patents.Publication numberUS7550143 B2Publication typeGrantApplication numberUS 11/389,358Publication dateJun 23, 2009Filing dateMar 24, 2006Priority dateApr 6, 2005Fee statusPaidAlso published asUS8163291, US8932593, US9540618, US20060228357, US20110008251, US20120196346, US20150056680Publication number11389358, 389358, US 7550143 B2, US 7550143B2, US-B2-7550143, US7550143 B2, US7550143B2InventorsChien Hsing Chang, David M. Goldenberg, William J. McBride, Edmund A. RossiOriginal AssigneeIbc Pharmaceuticals, Inc.Export CitationBiBTeX, EndNote, RefManPatent Citations (14), Non-Patent Citations (38), Referenced by (102), Classifications (43), Legal Events (3) External Links: USPTO, USPTO Assignment, EspacenetMethods for generating stably linked complexes composed of homodimers, homotetramers or dimers of dimers and uses
US 7550143 B2Abstract
1. A composition comprising a homodimer, each monomer of the homodimer comprising a dimerization and docking domain (DDD) attached to an antigen-binding antibody fragment, wherein the DDD consists of the sequence of SEQ ID NO:1 (DDD1) or SEQ ID NO:2 (DDD2).
2. The composition of claim 1, wherein the monomer is a fusion protein comprising the antigen-binding antibody fragment and the DDD.
3. The composition of claim 1, wherein the antigen-binding antibody fragment is chemically linked to the DDD.
4. The composition of claim 2, wherein the monomer further comprising a linker peptide between the antigen-binding antibody fragment and the DDD.
5. The composition of claim 2, wherein the antigen-binding antibody fragment comprises an Fd fragment of an antibody.
6. The composition of claim 1 wherein the antigen-binding antibody fragment is an Fab fragment.
7. The composition of claim 1, wherein the antigen-binding antibody fragment is from an antibody selected from the group consisting of a humanized antibody, a human antibody and a chimeric antibody.
8. The composition of claim 6, wherein the Fab fragment is selected from the group consisting of the Fab fragments of anti-CEA (hMN-14), anti-CD20 (hA20), anti-CD22 (hLL2), anti-CD74 (hLL1), anti-MUC-1(hPAM4), anti-CD14, anti-CD111, omalizumab, muromonab, abciximab, infliximab, and palivizumab.
9. The composition of claim 1, wherein the antigen-binding antibody fragment comprises an immunoglobulin light chain (VL-CL) or an immunoglobulin Fc domain (CH2-CH3).
10. The composition of claim 9, wherein the cysteine at the carboxyl-terminus of the CL that connects the CL to CH1 is deleted or mutated to a non-cysteine.
11. The composition of claim 9, wherein the immunoglobulin light chain or the Fc domain is selected from a human or humanized antibody.
12. The composition of claim 1, wherein the homodimer further comprises one or more effectors or carriers conjugated to the homodimer by either covalent or non-covalent linkage.
13. The composition of claim 12, wherein the effector is a diagnostic agent, a therapeutic agent, a chemotherapeutic agent, a radioisotope, an imaging agent, an anti-angiogenic agent, a cytokine, a chemokine, a growth factor, a drug, a prodrug, an enzyme, a binding molecule, a ligand for a cell surface receptor, a chelator, an immunomodulator, an oligonucleotide, a hormone, a photodetectable label, a dye, a peptide, a toxin, a contrast agent, a paramagnetic label, an ultrasound label, a pro-apoptotic agent, a liposome, a nanoparticle or a combination thereof.
14. The composition of claim 13, wherein the therapeutic agent is abrin, amantadine, amoxicillin, amphotericin B, ampicillin, aplidin, azaribine, anastrozole, azacytidine, aztreonam, azithromycin, bacitracin, bactrim, Batrafen, bifonazole, bleomycin, bortezomib, bryostatin-1, busulfan, calicheamycin, camptothecin, 10-hydroxycamptothecin, carbenicillin, caspofungin, carmustine, cefaclor, cefazolm, cephalosporins, cefepime, ceftriaxone, cefotaxime, celebrex, chlorambucil, chloramphenicol, ciprofloxacin, cisplatin, irinotecan (CPT-11), SN-38, carboplatin, cladribine, cyclophosphamide, cytarabine, dacarbazine, docetaxel, dactinomycin, daunomycin glucuronide, daunorubicin, dexamethasone, diethylstilbestrol, diphtheria toxin, DNase I, doxorubicin, 2-pyrrolinodoxorubicine (2P-DOX), doxycycline, cyano-morpholino doxorubicin, doxorubicin glucuronide, epirubicin giucuronide, ethinyl estradiol, estramustine, estrogen receptor binding agents, etoposide, etoposide glucuronide, etoposide phosphate, erythrocycline, erythromycin, flagyl, famesyl-protein transferase inhibitors, floxuridine (FUdR), 3′,5′-O-dioleoyl-FudR (FUdR-dO), fludarabine, flutamide, fluorouracil, fluoxymesterone, ganciclovir, gentamycin, gelonin, gemcitabine, hydroxyprogesterone caproate, hydroxyurea, idarubicin, ifosfamide, isoniazid, itraconazole, kanamycin, ketoconazole, L-asparaginase, leucovorin, lomustine, mechlorethamine, medroprogesterone acetate, megestrol acetate, melphalan, mercaptopurine, 6-mercaptopurine, methotrexate, mitoxantrone, mithramycin, mitomycin, mitotane, minocycline, naftifine, nalidixic acid, neomycin, navelbine, nitrosurea, nystatin, onconase, oxacillin, paromomycin, penicillin, pentamidine, piperacillin-tazobactam, phenyl butyrate, prednisone, procarbazine, paclitaxel, pentostatin, pokeweed antiviral protein, PSI-341, Pseudomonas exotoxin, Pseudomonas endotoxin, raloxifene, rapLR1, ribonuclease, ricin, semustine, rifabutin, rifampin, rimantadine, streptomycin, sulfamethoxazole, sulfasalazine, Staphylococcal enterotoxin-A, streptozocin, tamoxifen, taxanes, taxol, testosterone propionate, tetracycline, thalidomide, thioguanine, thiotepa, teniposide, topotecan, transplatinum, trimethoprim sulfamethoxazole, uracil mustard, valacyclovir, vancomycin, velcade, vinblastine, vinorelbine, vincristine, zanamir, zithromycin, an antisense oligonucleotide, an interference RNA, or a combination thereof.
15. The composition of claim 13, wherein the diagnostic or therapeutic agent is selected from the group consisting of 225Ac, 211At, 212Bi, 213Bi, 14C, 51Cr, 36Cl, 45Ti, 57Co, 58Co, 62Cu, 64Cu, 67Cu, 166Dy, 152Eu, 18F, 67Ga, 195mHg, 166Ho, 3H, 111In, 123I, 124I, 125I, 131I, 52Fe, 59Fe, 177Lu, 191Os, 212Pb, 32P, 33P, 142Pr, 195mPt, 223Ra, 186Re, 188Re, 189Re, 47Sc, 75Se 111Ag, 153Sm, 89Sr, 35S, 161Tb, 94mTc, 99mTc, 86Y, 90Y, and 89Zr.
16. The composition of claim 13, wherein the imaging agent is selected from the group consisting of chromium (III), manganese (II), iron (III), iron (II), cobalt (II), nickel (II), copper (II), neodymium (III), samarium (III), ytterbium (III), gadolinium (III, vanadium (II), terbium (III), dysprosium (III), holmium (III) erbium (III), lanthanum (III), gold (III), lead (II) and bismuth (III).
17. The composition of claim 13, wherein the photodetectable label is selected from the group consisting of Alexa 350, Alexa 430, AMCA, aminoacridine, BODIPY 630/650, BODIPY 650/665, BODIPY-FL, BODIPY-R6G, BODIPY-TMR, BODIPY-TRX, 5-carboxy-4′, 5′-dichloro-2′,7′-dimethoxy fluorescein, 5-carboxy-2′,4′,5′,7′-tetrachlorofluorescein, 5-carboxyfluorescein, 5-carboxyrhodamine, 6-carboxyrhodamine, 6-carboxytetramethyl amino, Cascade Blue, Cy2, Cy3, Cy5,6-FAM, dansyl chloride, Fluorescein, HEX, 6-JOE, NBD (7-nitrobenz-2-oxa-1,3-diazole), Oregon Green 488, Oregon Green 500, Oregon Green 514, Pacific Blue, phthalic acid, terephthalic acid, isophthalic acid, cresyl fast violet, cresyl blue violet, brilliant cresyl blue, para-aminobenzoic acid, erytlirosine, phthalocyanines, azomethines, cyanines, xanthines, succinylfluoresceins, rare earth metal cryptates, europium trisbipyridine diamine, a europium cryptate or chelate, diamine, dicyanins, La Jolla blue dye, allopycocyanin, allococyanin B, phycocyanin C, phycocyanin R, thiamine, phycoerythrocyanin, phycoerythrin R, REG, Rhodamine Green, rhodamine isothiocyanate, Rhodamine Red, ROX, TAMRA, TET, TRIT (tetramethyl rhodamine isothiol), Tetramethyirhodamine, and Texas Red.
18. The composition of claim 12, wherein the effectors or carriers are chemically cross-linked to the homodimer.
19. The composition of claim 12, wherein the homodimer is attached to two or more effectors or two or more carriers.
20. The composition of claim 19, wherein the two or more carriers or two or more effectors are either identical or different.
21. The composition of claim 12, wherein the one or more carriers comprise at least one diagnostic or therapeutic agent. Description
This application claims the benefit under 35 U.S.C. § 119(e) of provisional U.S. patent application Ser. No. 60/668,603, filed Apr. 6, 2005; 60/728,292, filed Oct. 19, 2005; 60/751,196, filed Dec. 16, 2005; and 60/782,332, entitled “Improved stably tethered structures of defined compositions with multiple functions or binding specificities, by Chang et al., filed Mar. 14, 2006. The text of each of the priority applications is incorporated herein by reference in its entirety.
In other embodiments, the stably tethered structures may be of use to treat infection with pathogenic organisms, such as bacteria, viruses or fungi. Exemplary fungi that may be treated include Microsporum, Trichophyton, Epidermophyton, Sporothrix schenckii, Cryptococcus neoformans, Coccidioides immitis, Histoplasma capsulatum, Blastomyces dermatitidis or Candida albican. Exemplary viruses include human immunodeficiency virus (HIV), herpes virus, cytomegalovirus, rabies virus, influenza virus, human papilloma virus, hepatitis B virus, hepatitis C virus, Sendai virus, feline leukemia virus, Reo virus, polio virus, human serum parvo-like virus, simian virus 40, respiratory syncytial virus, mouse mammary tumor virus, Varicella-Zoster virus, Dengue virus, rubella virus, measles virus, adenovirus, human T-cell leukemia viruses, Epstein-Barr virus, murine leukemia virus, mumps virus, vesicular stomatitis virus, Sindbis virus, lymphocytic choriomeningitis virus or blue tongue virus. Exemplary bacteria include Bacillus anthracis, Streptococcus agalactiae, Legionella pneumophilia, Streptococcus pyogenes, Escherichia coli, Neisseria gonorrhoeae, Neisseria meningitidis, Pneumococcus spp., Hemophilis influenzae B, Treponema pallidum, Lyme disease spirochetes, Pseudomonas aeruginosa, Mycobacterium leprae, Brucella abortus, Mycobacterium tuberculosis or a Mycoplasma. Although not limiting, in various embodiments, the precursors incorporated into the monomers, dimers and/or tetramers may comprise one or more proteins, such as a bacterial toxin, a plant toxin, ricin, abrin, a ribonuclease (RNase), DNase I, Staphylococcal enterotoxin-A, pokeweed antiviral protein, gelonin, diphtherin toxin, Pseudomonas exotoxin, Pseudomonas endotoxin, Ranpimase (Rap), Rap (N69Q), PE38, dgA, DT390, PLC, tPA, a cytokine, a growth factor, a soluble receptor component, surfactant protein D, IL-4, sIL-4R, sIL-13R, VEGF121, TPO, EPO, a clot-dissolving agent, an enzyme, a fluorescent protein, sTNFα-R, an avimer, a scFv, a dsFv or a nanobody.
Additional moieties can be conjugated to the stably tethered structures described above. For example, drugs, toxins, radioactive compounds, enzymes, hormones, cytotoxic proteins, chelates, cytokines, and other functional agents may be conjugated to the stably tethered structures. Conjugation can be via, for example, covalent attachments to amino acid residues containing amine, carboxyl, thiol or hydroxyl groups in the side-chains. Various conventional linkers may be used for this purpose, for example, diisocyanates, diisothiocyanates, bis(hydroxysuccinimide) esters, carbodiimides, maleimide-hydroxysuccinimide esters, glutaraldehyde and the like. Conjugation of agents to the stably tethered structures preferably does not significantly affect the activity of each subunit contained in the unmodified structures. Conjugation can be carried out separately to the a4 and a′4 constructs and the resulting conjugates are used for preparing the a2a′2 constructs In addition, cytotoxic agents may be first coupled to a polymeric carrier, which is then conjugated to a stably tethered structure. For this method, see Ryser et al., Proc. Natl. Acad. Sci. USA, 75:3867-3870, 1978; U.S. Pat. No. 4,699,784 and U.S. Pat. No. 4,046,722, which are incorporated herein by reference.
Nanoparticles or nanocapsules formed from polymers, silica, or metals, which are useful for drug delivery or imaging, have been described as well. See, e.g., West et al., Applications of Nanotechnology to Biotechnology (2000), 11:215-217; U.S. Pat. Nos. 5,620,708; 5,702,727; and 6,530,944. The conjugation of antibodies or binding molecules to liposomes to form a targeted carrier for therapeutic or diagnostic agents has been described. See, e.g., Bendas, Biodrugs (2001), 15:215-224; Xu et al., Mol. Cancer Ther (2002), 1:337-346; Torchilin et al., Proc. Nat'l. Acad. Sci. U.S.A (2003), 100:6039-6044; Bally, et al., J. Liposome Res.(1998), 8:299-335; Lundberg, Int. J. Pharm. (1994), 109:73-81; Lundberg, J. Pharm. Pharmacol. (1997), 49:16-21; Lundberg, Anti-cancer Drug Design (1998), 13: 453-461. See also U.S. Pat. No. 6,306,393; U.S. Ser. No. 10/350,096; U.S. Ser. No. 09/590,284, and U.S. Ser. No. 60/138,284, filed Jun. 9, 1999. All these references are incorporated herein by reference.
A suitable peptide containing a detectable label (e.g., a fluorescent molecule), or a cytotoxic agent, (e.g., a radioiodine), can be covalently, non-covalently, or otherwise associated with the stably tethered structures. For example, a therapeutically useful conjugate can be obtained by incorporating a photoactive agent or dye onto the stably tethered structures. Fluorescent compositions, such as fluorochrome, and other chromogens, or dyes, such as porphyrins sensitive to visible light, have been used to detect and to treat lesions by directing the suitable light to the lesion. In therapy, this has been termed photoradiation, phototherapy, or photodynamic therapy. See Jori et al. (eds.), PHOTODYNAMIC THERAPY OF TUMORS AND OTHER DISEASES (Libreria Progetto 1985); van den Bergh, Chem. Britain (1986), 22:430. Moreover, monoclonal antibodies have been coupled with photoactivated dyes for achieving phototherapy. See Mew et al., J. Immunol. (1983),130:1473; idem., Cancer Res. (1985), 45:4380; Oseroff et al., Proc. Natl. Acad. Sci. USA (1986), 83:8744; idem., Photochem. Photobiol. (1987), 46:83; Hasan et al., Prog. Clin. Biol. Res. (1989), 288:471; Tatsuta et al., Lasers Surg. Med. (1989), 9:422; Pelegrin et al., Cancer (1991), 67:2529. Endoscopic applications are also contemplated. Endoscopic methods of detection and therapy are described in U.S. Pat. Nos. 4,932,412; 5,525,338; 5,716,595; 5,736,119; 5,922,302; 6,096,289; and 6,387,350, which are incorporated herein by reference in their entirety.
Some embodiments of the claimed methods and/or compositions may concern antibody fragments. Such antibody fragments may be obtained by pepsin or papain digestion of whole antibodies by conventional methods. For example, antibody fragments may be produced by enzymatic cleavage of antibodies with pepsin to provide F(ab′)2 fragments . This fragment may be further cleaved using a thiol reducing agent and, optionally, followed by a blocking group for the sulfhydryl groups resulting from cleavage of disulfide linkages, to produce Fab′ monovalent fragments. Alternatively, an enzymatic cleavage using papain n produces two monovalent Fab fragments and an Fc fragment. Exemplary methods for producing antibody fragments are disclosed in U.S. Pat. Nos. 4,036,945; 4,331,647; Nisonoffet al., 1960, Arch. Biochem. Biophys., 89:230; Porter, 1959, Biochem. J., 73:119; Edelman et al., 1967, METHODS IN ENZYMOLOGY, page 422 (Academic Press), and Coligan et al. (eds.), 1991, CURRENT PROTOCOLS IN IMMUNOLOGY, (John Wiley & Sons).
In one non-limiting example of this methodology, Dantas-Barbosa et al. (2005) constructed a phage display library of human Fab antibody fragments from osteosarcoma patients. Generally, total RNA was obtained from circulating blood lymphocytes (Id.). Recombinant Fab were cloned from the μ, δ and κ chain antibody repertoires and inserted into a phage display library (Id.). RNAs were converted to cDNAs and used to make Fab cDNA libraries using specific primers against the heavy and light chain immunoglobulin sequences (Marks et al., 1991, J. Mol. Biol. 222:581-97, incorporated herein by reference). Library construction was performed according to Andris-Widhopf et al. (2000, In: Phage Display Laboratory Manual, Barbas et al. (eds), 1st edition, Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y., pp. 9.1 to 9.22, incorporated herein by reference). The final Fab fragments were digested with restriction endonucleases and inserted into the bacteriophage genome to make the phage display library. Such libraries may be screened by standard phage display methods, as known in the art. The skilled artisan will realize that this technique is exemplary only and any known method for making and screening human antibodies or antibody fragments by phage display may be utilized.
Pre-targeting methods have been developed to increase the target:background ratios of detection or therapeutic agents. Examples of pre-targeting and biotin/avidin approaches are described, for example, in Goodwin et al., U.S. Pat. No. 4,863,713; Goodwin et al., J. Nucl. Med. 29:226, 1988; Hnatowich et al., J. Nucl. Med. 28:1294, 1987; Oehr et al., J. Nucl. Med. 29:728, 1988; Klibanov et al., J. Nucl. Med. 29:1951, 1988; Sinitsyn et al., J. Nucl. Med. 30:66, 1989; Kalofonos et al., J. Nucl. Med. 31:1791, 1990; Schechter et al., Int. J. Cancer 48:167, 1991; Paganelli et al., Cancer Res. 51:5960,1991; Paganelli et al., Nucl. Med. Commun. 12:211, 1991; U.S. Pat. No. 5,256,395; Stickney et al., Cancer Res. 51:6650, 1991; Yuan et al., Cancer Res. 51:3119, 1991; U.S. Pat. No. 6,077,499; U.S. Ser. Nos. 09/597,580; 10/361,026; 09/337,756; 09/823,746; 10/116,116; 09/382,186; 10/150,654; U.S. Pat. Nos. 6,090,381; 6,472,511; U.S. Ser. No. 10/114,315; U.S. Provisional Application No. 60/386,411; U.S. Provisional Application No. 60/345,641; U.S. Provisional Application No. 60/3328,835; U.S. Provisional Application No. 60/426,379; U.S. Ser. Nos. 09/823,746; 09/337,756; and U.S. Provisional Application No. 60/342,103, all of which are incorporated herein by reference.
Methods for preparation and screening of aptamers that bind to particular targets of interest are well known, for example U.S. Pat. Nos. 5,475,096 and 5,270,163, each incorporated by reference. The technique generally involves selection from a mixture of candidate aptamers and step-wise iterations of binding, separation of bound from unbound aptamers and amplification. Because only a small number of sequences (possibly only one molecule of aptamer) corresponding to the highest affinity aptamers exist in the mixture, it is generally desirable to set the partitioning criteria so that a significant amount of aptamers in the mixture (approximately 5-50%) is retained during separation. Each cycle results in an enrichment of aptamers with high affinity for the target. Repetition for between three to six selection and amplification cycles may be used to generate aptamers that bind with high affinity and specificity to the target.
General Strategy for Producing Fab-Based Subunits with the DDD1 Sequence Appended to Either the C— or N-Terminus of the Fd Chain
GSGGGGSGGGGSHIQIPPGLTELLQGYTVEVLRQQPPDLVEFAVEYFTRL REARA
1–44 stop Eag Right
Methods for Generating a2 Constructs Composed of Two Identical Fab Subunits Stably Linked via the DDD1 Sequence Fused to Either the C— or N-Terminus of the Fd Chain
Rap-hPAM4-Fd-DDD1-pdHL2 is an expression vector for producing an a2 construct that comprises two identical Fab fusion proteins, each containing ranpimase (Rap) and the DDD1 sequence linked to the N-terminus of the light chain and the C-terminus of the Fd chain, respectively. hPAM4 is a humanized monoclonal antibody specific for MUC-1. The plasmid vector Rap-hPAM4-γl -pdHL2 used for producing the immunotoxin referred to as 2L-Rap(N69Q)-hPAM4, which is composed of two molecules of Rap, each fused to the N-terminus of the light chain of hPAM4, was digested with Sac2 and NgoM4 to remove the fragment encoding the CH1-CH3 domains, followed by ligation of the CH1-DDD1 fragment, which was excised from the plasmid vector C-DDD1-Fd-hMN-14-pdHL2 with Sac2 and NgoM4 to generate Rap-hPAM4-Fd-DDD1-pdHL2.
Treating transplant rejection as indicated
by OKT3 ® (muromonab)
Treating thrombosis as indicated by REOPRO ®
(adalimuab) or REMICADE ® (infliximab)
RSV therapy as indicated by SYNAGIS ®
Patent CitationsCited PatentFiling datePublication dateApplicantTitleUS4046722Jan 14, 1976Sep 6, 1977G. D. Searle & Co. LimitedImmunological materialsUS4699784Feb 25, 1986Oct 13, 1987Center For Molecular Medicine & ImmunologyTumoricidal methotrexate-antibody conjugateUS5770198 *Jan 17, 1995Jun 23, 1998The Research Foundation Of The State Of New YorkPlatelet-specific chimeric 7E3 immunoglobulinUS6261537 *Oct 29, 1997Jul 17, 2001Nycomed Imaging AsDiagnostic/therapeutic agents having microbubbles coupled to one or more vectorsUS6524854Sep 11, 2001Feb 25, 2003Isis Pharmaceuticals, Inc.Antisense inhibition of PKA regulatory subunit RII alpha expressionUS20030198956 *Feb 21, 2002Oct 23, 2003Lee MakowskiStaged assembly of nanostructuresUS20030232420 *May 1, 2003Dec 18, 2003Andreas BraunKinase anchor protein muteins, peptides thereof and related documentsUS20040018587Feb 21, 2003Jan 29, 2004Lee MakowskiNanostructures containing antibody assembly unitsUS20050003403Apr 22, 2004Jan 6, 2005Rossi Edmund A.Polyvalent protein complexUS20060228300Mar 28, 2006Oct 12, 2006Ibc Pharmaceuticals, Inc.Stably tethered structures of defined compositions with multiple functions or binding specificitiesUS20070086942Jun 29, 2006Apr 19, 2007Ibc Pharmaceuticals, Inc.Methods and compositions for generating bioactive assemblies of increased complexity and usesUS20070140966Dec 5, 2006Jun 21, 2007Ibc Pharmaceuticals, Inc.Multivalent immunoglobulin-based bioactive assembliesWO2000068248A2May 8, 2000Nov 16, 2000The Regents Of The University Of CaliforniaSelf assembling proteinsWO2007075270A2Dec 5, 2006Jul 5, 2007Ibc Pharmaceuticals, Inc.Multivalent immunoglobulin-based bioactive assemblies* Cited by examinerNon-Patent CitationsReference1Alto et al. "Bioinformatic design of A-kinase anchoring protein-in silico: A potent and selective peptide antagonist of type II protein kinase A anchoring," Proceedings of the National Academy of Science, Apr. 15, 2003, vol. 100, No. 8, pp. 4445-4450 [online]. [Retrieved on Feb. 19, 2007]. [Retrieved from the internet: http://www.pnas.org/cgi/reprint/100/8/4445].2 *Anonymus, Google search for the term "7E3", Aug. 13, 2008.3 *Banky et al, J Biol Chem 273(52): 35048-35055, 1998.4Banky et al. "Dimerization/Docking Domain of the Type lalpha Regulatory Subunit of cAMP-dependent Protein Kinase", J. Biol. Chem. 273:35048-55, 1998.5Banky et al. "Related Protein-Protein Interaction Modules Present Drastically Different Surface Topographies Despite A Conserved Helical Platform". J. Mol. Biol. (2003) 330, 1117-1129.6Carr et al., "Interaction of the Regulatory Subunit (RII) of cAMP-dependent Protein Kinase with RII-anchoring Proteins Occurs through an Amphipathic Helix Binding Motif", J. Biol. Chem. 266:14188-92 (1991).7 *Chang et al, Clin Cancer Res 13(18 Suppl): 5586s-5591s, Sep. 15, 2007.8Chang et al. "The Dock and Lock Method: A Novel Platform Technology for Building Multivalent, Multifunctional Structures of Defined Composition with Retained Bioactivity", Clin Cancer Res Sep. 15, 2007;13(18 Suppl), pp. 5586-5591.9Colledge et al. "AKAPs: from structure to function", Trends Cell Biol. 6:216-21 (1999).10Corbin et al. "Regulation of Adenosine 3',5'-Monophosphate-dependent Protein Kinase", J. Biol. Chem. 248:1813-21 (1973).11Gillies et al. "High-level expression of chimeric antibodies using adapted cDNA variable region cassettes", J. Immunol. Methods 125 (1989) 191-202.12Gold et al. "A Novel Bispecific, Trivalent Antibody Construct for Targeting Pancreatic Carcinoma", Cancer Res. 68:4819-26, 2008.13Goldenberg et al. "Multifunctional Antibodies by the Dock-and-Lock Method for Improved Cancer Imaging and Therapy by Pretargeting", J. Nucl. Med. 49:158-63, 2008.14Hausken et al. "Mutational Analysis of the A-Kinase Anchoring Protein (AKAP)-binding Site on RII", J. Biol. Chem. 271:29016-22 (1996).15Hodneland et al. "Selective immobilization of proteins to self-assembled monolayers presenting active site-directed capture ligands", Proc. Natl. Acd. Sci. USA 2002; 99:5048-5052.16Lohmann et al. "High-affinity binding of the regulatory subunit (RII) of cAMP-dependent protein kinase to microtubule-associated and other cellular proteins", Proc. Natl. Acad. Sci. USA 81:6723-27 (1984).17 *Mason et al, Molecular Endocrinology 8(3): 325-332, 1994.18Mason, Anthony J. "Functional Analysis of the Cysteine Residues of Activin A", Mol. Endocrinol. 8:325-32, 1994.19Newlon et al. "A Novel Mechanism of PKA Anchoring Revealed by Solution Structures of Anchoring Complexes", EMBO J. 2001; 20:1651-1662.20Newlon et al. "The molecular basis for protein kinase A anchoring revealed by solution NMR", Nature Struct. Biol. 1999; 3:222-227.21 *Ngo et al, The Protein Folding Problem and Tertiary Structure Prediction, pp. 492-495, 1994.22Ngo et al. "Computational Complexity, Protein Structure Prediction, and the Levinthal Paradox", The Protein Folding Problem and Tertiary Structure Prediction, Ch. 14, pp. 491-495, (Mertz & Le Grand, Eds.), Birkhauser Boston, 1994.23 *Oyen et al, FEBS Letters 246(1-2): 57-64, Mar. 1989.24Oyen et al. "Human testis cDNA for the regulatory subunit RIIalpha of cAMP-dependent protein kinase encodes an alternate amino-terminal region", FEBS Letters 246:57-64, 1989.25Rose et al. "Structural basis of dimerization, coactivator recognition and MODY3 mutations in HNF-1alpha", Nature Struct. Biol. 2000; 7:744-748.26Rossi et al. "Novel Designs of Multivalent Anti-CD20 Humanized Antibodies as Improved Lymphoma Therapeutics", Cancer Res. 68:8384-92, 2008.27Rossi et al. "Stably tethered multifunctional structures of defined composition made by the dock and lock method for use in cancer targeting". Proc Natl Acad Sci Epub Apr. 24, 2006, vol. 103, No. 18, pp. 6841-6846.28Rustandi et al. "The Ca2+-Dependent Interaction of S100B (betabeta) with a Peptide Derived from p53", Biochemistry 1998; 37: 1951-1960.29Scott et al. "Type II Regulatory Subunit Dimerization Determines the Subcellular Localization of the cAMP-dependent Protein Kinase", J. Biol. Chem. 265:21561-66 (1990).30Sharkey et al. "Improved Therapeutic Results by Pretargeted Radioimmunotherapy of Non-Hodgkin's Lymphoma with a New Recombinant, Trivalent, Anti-CD20, Bispecific Antibody", Cancer Res. 68:5282-90, 2008.31Sharkey et al. "Metastatic Human Colonic Carcinoma: Molecular Imaging with Pretargeted SPECT and PET in a Mouse Model", Radiology 246:497-507, 2008.32 *Stryer et al, in Biochemistry, Third edition, W H Freeman Company, New York, pp. 31-33, 1998.33Stryer et al. "Levels of Structure in Protein Architecture", Biochemistry, 3rd Ed., pp. 31-33, W.H. Freeman & Co., New York, 1988.34 *Winkler et al, J Immunology 165: 4505-4514, 2000.35Winkler et al. "Changing the Antigen Binding Specificity by Single Point Mutations of an Anti-p24 (HIV-1) Antibody", J. Immunol. 165:4505-14, 2000.36Wong et al. "AKAP Signalling Complexes: Focal Points in Space and Time", Nat. Rev. Mol. Cell Biol. 12:959-70 (2004).37 *Zhu et al, Investigational New Drugs 17: 195-212, 1999.38Zhu et al. "Inhibition of tumor growth and metastasis by targeting tumor-associated angiogenesis with antagonists to the receptors of vascular endothelial growth factor", Invest. New Drugs 17:195-212, 1999.* Cited by examinerReferenced byCiting PatentFiling datePublication dateApplicantTitleUS7858070 *Mar 3, 2009Dec 28, 2010Ibc Pharmaceuticals, Inc.Multivalent immunoglobulin-based bioactive assembliesUS7871622 *Mar 3, 2009Jan 18, 2011Ibc Pharmaceuticals, Inc.Stably tethered structures of defined compositions with multiple functions or binding specificitiesUS7901680 *Aug 20, 2009Mar 8, 2011Ibc Pharmaceuticals, Inc.Dock-and-lock (DNL) vaccines for cancer therapyUS7906118 *Apr 6, 2009Mar 15, 2011Ibc Pharmaceuticals, Inc.Modular method to prepare tetrameric cytokines with improved pharmacokinetics by the dock-and-lock (DNL) technologyUS7906121Apr 3, 2009Mar 15, 2011Ibc Pharmaceuticals, Inc.Methods and compositions for generating bioactive assemblies of increased complexity and usesUS7981398 *Dec 22, 2009Jul 19, 2011Ibc Pharmaceuticals, Inc.PEGylation by the dock and lock (DNL) techniqueUS8003111 *Mar 25, 2010Aug 23, 2011Ibc Pharmaceuticals, Inc.Dimeric alpha interferon pegylated site-specifically shows enhanced and prolonged efficacy in vivoUS8034352Apr 1, 2010Oct 11, 2011Ibc Pharmaceuticals, Inc.Tetrameric cytokines with improved biological activityUS8067006Apr 23, 2010Nov 29, 2011Immunomedics, Inc.Polymeric carriers of therapeutic agents and recognition moieties for antibody-based targeting of disease sitesUS8158129Jul 7, 2011Apr 17, 2012Ibc Pharmaceuticals, Inc.Dimeric alpha interferon PEGylated site-specifically shows enhanced and prolonged efficacy in vivoUS8163291 *May 19, 2009Apr 24, 2012Ibc Pharmaceuticals, Inc.Methods for generating stably linked complexes composed of homodimers, homotetramers or dimers of dimers and usesUS8211440Nov 18, 2010Jul 3, 2012Ibc Pharmaceuticals, Inc.Multivalent immunoglobulin-based bioactive assembliesUS8246960Feb 4, 2011Aug 21, 2012Ibc Pharmaceuticals, Inc.Methods and compositions for generating bioactive assemblies of increased complexity and usesUS8277817Jun 1, 2011Oct 2, 2012Ibc Pharmaceuticals, Inc.PEGylation by the dock and lock (DNL) techniqueUS8282934Jan 25, 2011Oct 9, 2012Ibc Pharmaceuticals, Inc.Modular method to prepare tetrameric cytokines with improved pharmacokinetics by the dock-and-lock (DNL) technologyUS8287865Jul 29, 2010Oct 16, 2012Immunomedics, Inc.Class I anti-CEA antibodies and uses thereofUS8338140Sep 27, 2011Dec 25, 2012Immunomedics, Inc.Polymeric carriers of therapeutic agents and recognition moieties for antibody-based targeting of disease sitesUS8349332Apr 14, 2011Jan 8, 2013Ibc Pharmaceuticals, Inc.Multiple signaling pathways induced by hexavalent, monospecific and bispecific antibodies for enhanced toxicity to B-cell lymphomas and other diseasesUS8435539Dec 9, 2010May 7, 2013Immunomedics, Inc.Delivery system for cytotoxic drugs by bispecific antibody pretargetingUS8435540Mar 6, 2012May 7, 2013Ibc Pharmaceuticals, Inc.Dimeric alpha interferon PEGylated site-specifically shows enhanced and prolonged efficacy in VIVOUS8470994Sep 7, 2012Jun 25, 2013Immunomedics, Inc.Class I anti-CEA antibodies and uses thereofUS8475794Aug 15, 2011Jul 2, 2013Ibc Pharmaceuticals, Inc.Combination therapy with anti-CD74 antibodies provides enhanced toxicity to malignancies, Autoimmune disease and other diseasesUS8481041Nov 3, 2011Jul 9, 2013Ibc Pharmaceuticals, Inc.Dock-and-lock (DNL) constructs for human immunodeficiency virus (HIV) therapyUS8491914Dec 9, 2010Jul 23, 2013Ibc Pharmaceuticals, Inc.Dock-and-lock (DNL) complexes for delivery of interference RNAUS8551480Aug 30, 2010Oct 8, 2013Immunomedics, Inc.Compositions and methods of use of immunotoxins comprising ranpirnase (Rap) show potent cytotoxic activityUS8562988Apr 6, 2010Oct 22, 2013Ibc Pharmaceuticals, Inc.Strategies for improved cancer vaccinesUS8597659Aug 29, 2011Dec 3, 2013Ibc Pharmaceuticals, Inc.Tetrameric cytokines with improved biological activityUS8603479May 21, 2013Dec 10, 2013Immunomedics, Inc.Class I anti-CEA antibodies and uses thereofUS8652484Dec 11, 2012Feb 18, 2014Immunomedics, Inc.Delivery system for cytotoxic drugs by bispecific antibody pretargetingUS8658773May 1, 2012Feb 25, 2014Immunomedics, Inc.Ultrafiltration concentration of allotype selected antibodies for small-volume administrationUS8722047Apr 5, 2010May 13, 2014Immunomedics, Inc.Humanized anti-HLA-DR antibodiesUS8771690Oct 29, 2013Jul 8, 2014Immunomedics, Inc.Class I anti-CEA antibodies and uses thereofUS8865176Jul 16, 2012Oct 21, 2014Ibc Pharmaceuticals, Inc.Methods and compositions for generating bioactive assemblies of increased complexity and usesUS8871216Nov 5, 2012Oct 28, 2014Ibc Pharmaceuticals, Inc.Multiple signaling pathways induced by hexvalent, monospecific and bispecific antibodies for enhanced toxicity to B-cell lymphomas and other diseasesUS8883160 *Feb 28, 2011Nov 11, 2014Ibc Pharmaceuticals, Inc.Dock-and-lock (DNL) complexes for therapeutic and diagnostic useUS8883162Nov 29, 2012Nov 11, 2014Ibc Pharmaceuticals, Inc.Multivalent antibody complexes targeting IGF-1R show potent toxicity against solid tumorsUS8889835Nov 7, 2012Nov 18, 2014Immunomedics, Inc.Polymeric carriers of therapeutic agents and recognition moieties for antibody-based targeting of disease sitesUS8906377Dec 15, 2010Dec 9, 2014Ibc Pharmaceuticals, Inc.Stably tethered structures of defined compositions with multiple functions or binding specificitiesUS8906378May 29, 2013Dec 9, 2014Ibc Pharmaceuticals, Inc.Combination therapy with anti-CD74 antibodies provides enhanced toxicity to malignancies, autoimmune disease and other diseasesUS8932593Mar 14, 2012Jan 13, 2015Ibc Pharmaceuticals, Inc.Methods for generating stably linked complexes composed of homodimers, homotetramers or dimers of dimers and usesUS8945554May 28, 2014Feb 3, 2015Immunomedics, Inc.Class I anti-CEA antibodies and uses thereofUS9139649Jan 22, 2015Sep 22, 2015Immunomedics, Inc.Humanized anti-CD22 antibodyUS9139657Dec 19, 2014Sep 22, 2015Immunomedics, Inc.Class I anti-CEA antibodies and uses thereofUS9169470Sep 17, 2014Oct 27, 2015Ibc Pharmaceuticals, Inc.Methods and compositions for generating bioactive assemblies of increased complexity and usesUS9180205Jan 24, 2014Nov 10, 2015Immunomedics, Inc.Stable compositions of high-concentration allotype-selected antibodies for small-volume administrationUS9187561Mar 25, 2014Nov 17, 2015Immunomedics, Inc.Humanized anti-HLA-DR antibodiesUS9248184May 31, 2013Feb 2, 2016Ibc Pharmaceuticals, Inc.Dock-and-lock (DNL) constructs for human immunodeficiency virus (HIV) therapyUS9272029Jan 25, 2013Mar 1, 2016Ibc Pharmaceuticals, Inc.Interferon lambada-antibody complexesUS9315567Aug 14, 2013Apr 19, 2016Ibc Pharmaceuticals, Inc.T-cell redirecting bispecific antibodies for treatment of diseaseUS9352036Nov 7, 2013May 31, 2016Immunomedics, Inc.Delivery system for cytotoxic drugs by bispecific antibody pretargetingUS9359443Oct 22, 2014Jun 7, 2016Ibc Pharmaceuticals, Inc.Combination therapy with anti-CD74 and anti-CD20 antibodies provides enhanced toxicity to B-cell diseasesUS9371393Aug 13, 2015Jun 21, 2016Immunomedics, Inc.Class I anti-CEA antibodies and uses thereofUS9382329Jan 20, 2015Jul 5, 2016Ibc Pharmaceuticals, Inc.Disease therapy by inducing immune response to Trop-2 expressing cellsUS9416197Oct 28, 2014Aug 16, 2016Ibc Pharmaceuticals, Inc.Bispecific antibodies that neutralize both TNF-α and IL-6: novel therapeutic agent for autoimmune diseaseUS9441043Jan 16, 2015Sep 13, 2016Immunomedics, Inc.Methods of treating cancer with antibodies that target the insulin-like growth factor type I receptor (IGF-1R)US9446123May 24, 2013Sep 20, 2016Ibc Pharmaceuticals, Inc.Multimeric complexes with improved in vivo stability, pharmacokinetics and efficacyUS9457072Jan 21, 2011Oct 4, 2016Ibc Pharmaceuticals, Inc.Dock-and-lock (DNL) vaccines for cancer therapyUS9457100Aug 20, 2012Oct 4, 2016Ibc Pharmaceuticals, Inc.PEGylation by the dock and lock (DNL) techniqueUS9468689Dec 18, 2013Oct 18, 2016Immunomedics, Inc.Ultrafiltration concentration of allotype selected antibodies for small-volume administrationUS9481878Sep 4, 2013Nov 1, 2016Immunomedics, Inc.Compositions and methods of use of immunotoxins comprising ranpirnase (Rap) show potent cytotoxic activityUS9492561Jun 3, 2013Nov 15, 2016Ibc Pharmaceuticals, Inc.Dock-and-Lock (DNL) Complexes for delivery of interference RNAUS9498542Oct 30, 2013Nov 22, 2016Immunomedics, Inc.Tetrameric cytokines with improved biological activityUS9518115Aug 12, 2015Dec 13, 2016Immunomedics, Inc.Humanized anti-CD22 antibodyUS9540435Oct 22, 2014Jan 10, 2017Ibc Pharmaceuticals, Inc.Stably tethered structures of defined compositions with multiple functions or binding specificitiesUS9540618Nov 5, 2014Jan 10, 2017Ibc Pharmaceuticals, Inc.Methods for generating stably linked complexes composed of homodimers, homotetramers or dimers of dimers and usesUS9550838Oct 1, 2014Jan 24, 2017Ibc Pharmaceuticals, Inc.Dock-and-lock (DNL) complexes for therapeutic and diagnostic useUS9617531Sep 5, 2012Apr 11, 2017Ibc Pharmaceuticals, Inc.Modular method to prepare tetrameric cytokines with improved pharmacokinetics by the dock-and-lockUS9623115Nov 14, 2011Apr 18, 2017Ibc Pharmaceuticals, Inc.Dock-and-Lock (DNL) Complexes for Disease TherapyUS9670286Jun 1, 2016Jun 6, 2017Ibc Pharmaceuticals, Inc.Disease therapy by inducing immune response to Trop-2 expressing cellsUS9682143Dec 14, 2013Jun 20, 2017Ibc Pharmaceuticals, Inc.Combination therapy for inducing immune response to diseaseUS9683050Oct 6, 2015Jun 20, 2017Immunomedics, Inc.Stable compositions of high-concentration allotype-selected antibodies for small-volume administrationUS9687547May 25, 2016Jun 27, 2017Immunomedics, Inc.T20 constructs for anti-HIV (human immunodeficiency virus) therapy and/or vaccinesUS9701748Sep 13, 2016Jul 11, 2017Immunomedics, Inc.Humanized anti-CD22 antibodyUS20080171067 *Dec 20, 2007Jul 17, 2008Immunomedics, Inc.Polymeric Carriers of Therapeutic Agents and Recognition Moieties for Antibody-Based Targeting of Disease SitesUS20090191225 *Mar 3, 2009Jul 30, 2009Ibc Pharmaceuticals, Inc.Stably Tethered Structures of Defined Compositions with Multiple Functions or Binding SpecificitiesUS20090202433 *Apr 3, 2009Aug 13, 2009Ibc Pharmaceuticals, Inc.Methods and Compositions for Generating Bioactive Assemblies of Increased Complexity and UsesUS20090202487 *Apr 6, 2009Aug 13, 2009Ibc Pharmaceuticals, Inc.Modular Method to Prepare Tetrameric Cytokines with Improved Pharmacokinetics by the Dock-and-Lock (DNL) TechnologyUS20090269277 *Mar 3, 2009Oct 29, 2009Ibc Pharmaceuticals, Inc.Multivalent Immunoglobulin-Based Bioactive AssembliesUS20100068137 *Aug 20, 2009Mar 18, 2010Ibc Pharmaceuticals, Inc.Dock-and-Lock (DNL) Vaccines for Cancer TherapyUS20100189641 *Apr 6, 2010Jul 29, 2010Immunomedics, Inc.Novel Strategies for Improved Cancer VaccinesUS20100189689 *Apr 1, 2010Jul 29, 2010Ibc Pharmaceuticals, Inc.Tetrameric Cytokines with Improved Biological ActivityUS20100196266 *Apr 5, 2010Aug 5, 2010Immunomedics, Inc.Humanized Anti-HLA-DR AntibodiesUS20100221210 *Mar 25, 2010Sep 2, 2010Ibc Pharmaceuticals, Inc.Dimeric Alpha Interferon PEGylated Site-Specifically Shows Enhanced and Prolonged Efficacy in VivoUS20100226884 *Mar 12, 2010Sep 9, 2010Immunomedics, Inc.Novel Class of Monospecific and Bispecific Humanized Antibodies that Target the Insulin-like Growth Factor Type I Receptor (IGF-1R)US20100233779 *Apr 23, 2010Sep 16, 2010Immunomedics, Inc.Polymeric Carriers of Therapeutic Agents and Recognition Moieties for Antibody-Based Targeting of Disease SitesUS20100261885 *Dec 22, 2009Oct 14, 2010Ibc Pharmaceuticals, Inc.PEGylation by the Dock and Lock (DNL) TechniqueUS20110008251 *May 19, 2009Jan 13, 2011Ibc Pharmaceuticals, Inc.Methods for Generating Stably Linked Complexes Composed of Homodimers, Homotetramers or Dimers of Dimers and UsesUS20110020273 *Aug 27, 2010Jan 27, 2011Ibc Pharmaceuticals, Inc.Bispecific Immunocytokine Dock-and-Lock (DNL) Complexes and Therapeutic Use ThereofUS20110064653 *Jul 29, 2010Mar 17, 2011Immunomedics, Inc.Class I Anti-CEA Antibodies and Uses ThereofUS20110064754 *Oct 29, 2010Mar 17, 2011Center For Molecular Medicine And ImmunologyImmunoconjugates Comprising Poxvirus-Derived Peptides and Antibodies Against Antigen-Presenting Cells for Subunit-Based Poxvirus VaccinesUS20110076233 *Dec 9, 2010Mar 31, 2011Immunomedics, Inc.Delivery System for Cytotoxic Drugs by Bispecific Antibody PretargetingUS20110110851 *Nov 18, 2010May 12, 2011Ibc Pharmaceuticals, Inc.Multivalent Immunoglobulin-Based Bioactive AssembliesUS20110123436 *Dec 9, 2010May 26, 2011Ibc Pharmaceuticals, Inc.Dock-and-Lock (DNL) Complexes for Delivery of Interference RNAUS20110143417 *Dec 15, 2010Jun 16, 2011Ibc Pharmaceuticals, Inc.Stably Tethered Structures of Defined Compositions with Multiple Functions or Binding SpecificitiesUS20110158905 *Feb 28, 2011Jun 30, 2011Ibc Pharmaceuticals, Inc.Dock-and-Lock (DNL) Complexes for Therapeutic and Diagnostic UseUS20110171126 *Jan 11, 2011Jul 14, 2011Center For Molecular Medicine And ImmunologyEnhanced Cytotoxicity of Anti-CD74 and Anti-HLA-DR Antibodies with Interferon-GammaUS20110189083 *Jan 21, 2011Aug 4, 2011Ibc Pharmaceuticals, Inc.Dock-and-Lock (DNL) Vaccines for Cancer TherapyUS20110195020 *Feb 4, 2011Aug 11, 2011Ibc Pharmaceuticals, Inc.Methods and Compositions for Generating Bioactive Assemblies of Increased Complexity and UsesUS20110236352 *Jun 1, 2011Sep 29, 2011Ibc Pharmaceuticals, Inc.PEGylation by the Dock and Lock (DNL) TechniqueUS20130259800 *Dec 15, 2011Oct 3, 2013Biovista, Inc.Compositions and methods for cancer treatmentEP3009455A1Jul 29, 2010Apr 20, 2016Immunomedics Inc.Class i anti-cea antibodies and uses thereofWO2013188740A1Jun 14, 2013Dec 19, 2013Ambrx, Inc.Anti-psma antibodies conjugated to nuclear receptor ligand polypeptides* Cited by examinerClassifications U.S. Classification424/134.1, 424/185.1, 424/178.1, 530/388.85, 530/388.8, 530/350, 424/138.1, 424/193.1, 530/388.22, 424/192.1, 530/388.73, 424/198.1, 424/143.1, 424/152.1, 530/324, 424/144.1, 530/387.3, 530/388.7International ClassificationA61K39/395, A61K38/01, A61K38/19, C07K16/28, C07K16/46, C07K16/30Cooperative ClassificationC07K16/2803, C12N9/12, C12Y207/11011, C07K2319/00, C07K16/18, C07K16/3007, C07K2317/31, B82Y5/00, C07K2319/70, B82Y10/00, C07K16/2887, C07K2317/55, C07K16/3092European ClassificationB82Y10/00, B82Y5/00, C07K16/30A, C07K16/28U, C07K16/28A, C07K16/30S20Legal EventsDateCodeEventDescriptionApr 25, 2006ASAssignmentOwner name: IBC PHARMACEUTICALS, INC., NEW JERSEYFree format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNORS:CHANG, MR. CHIEN H.;GOLDENBERG, MR. DAVID M.;MCBRIDE, MR. WILLIAM J.;AND OTHERS;REEL/FRAME:017522/0084Effective date: 20060417Dec 13, 2012FPAYFee paymentYear of fee payment: 4Dec 12, 2016FPAYFee paymentYear of fee payment: 8RotateOriginal ImageGoogle Home - Sitemap - USPTO Bulk Downloads - Privacy Policy - Terms of Service - About Google Patents - Send FeedbackData provided by IFI CLAIMS Patent Services