Humanized antibodies specific to the protofibrillar form of the beta-amyloid peptide
| Title: | Humanized antibodies specific to the protofibrillar form of the beta-amyloid peptide |
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| Patent Number: | 8,614,299 |
| Publication Date: | December 24, 2013 |
| Appl. No: | 13/319710 |
| Application Filed: | May 11, 2010 |
| Abstract: | The present application relates to humanized antibodies specific to the protofibrillar form of the beta-amyloid peptide, and to the use of said antibodies in the field of Alzheimer's disease. |
| Inventors: | Baurin, Nicolas (Paris, FR); Blanche, Francis (Paris, FR); Cameron, Beatrice (Paris, FR); Duchesne, Marc (Paris, FR); Mikol, Vincent (Paris, FR); Naimi, Souad (Paris, FR); Pradier, Laurent (Paris, FR); Shi, Yi (Paris, FR) |
| Assignees: | Sanofi (Paris, FR) |
| Claim: | 1. A humanized antibody specific for the protofibrillar form of the A-βpeptide comprising CDRs of sequence SEQ ID NO: 10, 12, 14, 32, 18 and 20. |
| Claim: | 2. A humanized antibody specific for the protofibrillar form of the A-βpeptide comprising CDRs of sequence SEQ ID NO: 10, 12, 30, 32, 18 and 20. |
| Claim: | 3. A pharmaceutical composition comprising the humanized Antibody according to claim 1 or 2 and excipients. |
| Claim: | 4. A medical product comprising the humanized antibody according to claim 1 or 2 . |
| Claim: | 5. A humanized antibody specific for the protofibrillar form of the A-β peptide comprising CDRs of sequence SEQ ID NO: 10, 12, 14, 16, 18 and 20 characterized in that the variable part of its heavy chain comprises a sequence having at least 95% identity with SEQ ID NO: 6 or and the variable part of its light chain comprises a sequence having at least 95% identity with SEQ ID NO: 8. |
| Claim: | 6. A humanized antibody specific for the protofibrillar form of the Aβ peptide comprising CDRs of sequence SEQ ID NOs: 10, 12, 14, 16, 18 and 20, characterized in that the variable part of its heavy chain comprises a sequence having at least 95% identity with SEQ ID NO: 6 and the variable part of its light chain comprises a sequence having at least 99% identity with SEQ ID NO: 8. |
| Claim: | 7. A humanized antibody specific for the protofibrillar form of the Aβ peptide comprising CDRs of sequence SEQ ID NOs: 10, 12, 14, 16, 18 and 20, characterized in that the variable part of its heavy chain comprises a sequence having at least 99% identity with SEQ ID NO: 6 and the variable part of its light chain comprises a sequence having at least 99% identity with SEQ ID NO: 8. |
| Claim: | 8. A humanized antibody specific for the protofibrillar form of the A-β Peptide comprising CDRs of sequence SEQ ID NO: 10, 12, 14, 32, 18 and 20 characterized in that the variable part of its light chain comprises a sequence having at least 95% identity with SEQ ID NO 24 and the variable part of its heavy chain comprises a sequence having at least 95% identity with SEQ ID NO: 6. |
| Claim: | 9. A humanized antibody specific for the protofibrillar form of the Aβ peptide comprising CDRs of sequence SEQ ID NOs: 10, 12, 14, 32, 18 and 20, characterized in that the variable part of its light chain comprises a sequence having at least 99% identity with SEQ ID NO: 24 and the variable part of its heavy chain comprises a sequence having at least 99% identity with SEQ ID NO: 6. |
| Claim: | 10. A humanized antibody specific for the protofibrillar form of the Aβ peptide comprising CDRs of sequence SEQ ID NO: 10, 12, 30, 32, 18 and 20 characterized in that the variable part of its heavy chain comprises a sequence having at least 95% identity with SEQ ID NO 28 and the variable part of its light chain comprises a sequence having at least 95% identity with SEQ ID NO: 24. |
| Claim: | 11. A humanized antibody specific for the protofibrillar form of the Aβ peptide comprising CDRs of sequence SEQ ID NOs: 10, 12, 30, 32, 18 and 20, characterized in that the variable part of its heavy chain comprises a sequence having at least 99% identity with SEQ ID NO: 28 and the variable part of its light chain comprises a sequence having at least 99% identity with SEQ ID NO: 24. |
| Claim: | 12. A humanized antibody specific for the protofibrillar form of the A-βpeptide, wherein said antibody comprises a variable region of a heavy chain comprising SEQ ID NO:6 and a variable region of light chain comprising SEQ ID NO:8. |
| Claim: | 13. A humanized antibody specific for the protofibrillar form of the A-βpeptide, wherein said antibody comprises a heavy chain comprising SEQ ID NO:2 and a light chain comprising SEQ ID NO:4. |
| Claim: | 14. The antibody antibody according to claim 12 or 13 , characterized in that it induces a reduction of amyloid plaques. |
| Claim: | 15. The antibody according to claim 12 or 13 , characterized in that its affinity for the protofibrillar form of peptide Aβ is at least 100 times greater than its affinity for the other forms of this peptide. |
| Claim: | 16. A pharmaceutical composition comprising the humanized antibody according to claim 12 and excipients. |
| Claim: | 17. A pharmaceutical composition comprising the humanized antibody according to claim 13 and excipients. |
| Claim: | 18. A medicinal product comprising the humanized antibody according to claim 12 . |
| Claim: | 19. A medicinal product mprising the humanized antibody according to claim 13 . |
| Claim: | 20. A humanized antibody specific for the protofibrillar form of the Aβ peptide, wherein said antibody comprises a variable region of a heavy chain comprising SEQ ID NO:6 and a variable region of a light chain comprising SEQ ID NO:24. |
| Claim: | 21. A humanized antibody specific for the protofibrillar form of the A-β peptide, wherein said antibody comprises a heavy chain comprising SEQ ID NO:2 and a light chain comprising SEQ ID NO:22. |
| Claim: | 22. A pharmaceutical composition comprising the humanized antibody according to claim 20 or claim 21 and excipients. |
| Claim: | 23. A medicinal product comprising the humanized antibody according to claim 20 or claim 21 . |
| Claim: | 24. A humanized antibody specific for the protofibrillar form of the A-β peptide, wherein said antibody comprises a variable region of a heavy chain comprising SEQ ID NO:28 and a variable region of a light chain comprising SEQ ID NO:24. |
| Claim: | 25. A humanized antibody specific for the protofibrillar form of the A-β peptide, wherein said antibody comprises as heavy chain comprising SEQ ID NO:26 and a light chain comprising SEQ ID NO:22. |
| Claim: | 26. A pharmaceutical composition comprising the humanized antibody according to claim 24 or claim 25 and excipients. |
| Claim: | 27. A medicinal product comprising the humanized antibody according to claim 24 or claim 25 . |
| Current U.S. Class: | 5303/873 |
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| Other References: | MacCallum et al. (1996) J. Mol. Biol. 262:732-745. cited by examiner Padlan et al. (1989) Proc Natl Acad Sci USA, 86:5938-5942. cited by examiner Paul, WE (editor), Fundamental Immunology, Third Edition. Raven Press, New York, 1993, pp. 292-295. cited by examiner Rudikoff et al. (1982) Proc Natl Acad Sci USA, 79(6):1979-1983. cited by examiner Vajdos et al. (2002) J. Mol. Biol. 320(2):415-428. cited by examiner International Search Report WO2010/130946 dated Nov. 18, 2010. cited by applicant Angal et al., A Single Amino Acid Substitution Abolishes The Heterogeneity of Chimeric Mouse/Human (IgG4) Antibody, Molecular Immunology, vol. 30, No. 1, 1993, pp. 105-108. cited by applicant Duyckaerts et al., Diagnosis and Staging of Alzheimer's Disease, Neurobiology of Aging, vol. 18, S4, pp. 33-42, 1997, pp. S33-S42. cited by applicant Jellinger et al., Neuropathology of Alzheimer's disease: a critical update, J. Neural Transmission Supp., vol. 54, 1996, pp. 77-95. cited by applicant Lazar et al., A molecular immunology approach to antibody humanization and functional optimization, Molecular Immunology, vol. 44, 2007, pp. 1986-1998. cited by applicant Padlan et al., A Possible Procedure for Reducing The Immunogencity of Antibody Variable Domains While Preserving Their Ligand-Binding Properties, Molecular Immunology, vol. 28, No. 4/5 1991, pp. 489-498. cited by applicant Racke et al., Exacerbation of Cerebral Amyloid Angiopathy-Associated Microhemorrhage in Amyloid Precursor Protein Transgenic Mice by Immunotherapy is Dependent on Antibody Recognition of Deposited Forms of Amyloid Beta, J. of Neuroscience, vol. 25, No. 3, Jan. 19, 2005, pp. 629-626. cited by applicant Ratovsky et al., Choosing Near-Linear Parameters in the Four-Parameter Logistic Model for Radioligand and Related Assays, Biometrics, vol. 42, 1986, pp. 575-582. cited by applicant Roguska et al., Humanization of murine monoclonal antibodies through variable domain resurfacing, PNAS, vol. 91, 1994, pp. 969-973. cited by applicant Schmitz et al., Hippocampal Neuron Loss Exceeds Amyloid Plaque Load in a Transgenic Mouse Model of Alzheimers Disease, Am J. of Pathology, vol. 164, No. 4. Apr. 2004, pp. 1495-1502. cited by applicant Schupf et al., Peripheral ABeta subspecies as risk biomarkers of Alzheimer's disease, PNAS, vol. 105, No. 37, Sep. 16, 2008, pp. 14052-14057. cited by applicant Studnicka et al., Human-engineered monoclonal antibodies retain full specific binding activity by preserving non-CDR complementarity-modulating residues, Protein Engineering vol. 7, No. 6, 1994, pp. 805-814. cited by applicant Yanker, B., New clues to Alzheimer's disease: Unraveling the roles of amyloid and tau, Nature Medicine, vol. 2, No. 8, Aug. 1996, pp. 850-853. cited by applicant |
| Primary Examiner: | Ballard, Kimberly A |
| Attorney, Agent or Firm: | Szczepanik, Ann Marie |
| Accession Number: | edspgr.08614299 |
| Database: | USPTO Patent Grants |
| Language: | English |
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