Claims for Patent: 9,079,949

Summary for Patent: 9,079,949

Title:	Anti-C5 antibodies having improved pharmacokinetics
Abstract:	The disclosure provides antibodies that are useful for, among other things, inhibiting terminal complement (e.g., the assembly and/or activity of the C5b-9 TCC) and C5a anaphylatoxin-mediated inflammation and, thus, treating complement-associated disorders. The antibodies have a number of improved properties relative to eculizumab, including, e.g., increased serum half-life in a human.
Inventor(s):	Andrien, Jr.; Bruce A. (Guilford, CT), Sheridan; Douglas L. (Branford, CT), Tamburini; Paul P. (Kensington, CT)
Assignee:	ALEXION PHARMACEUTICALS, INC. (Cheshire, CT)
Application Number:	14/641,026
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 9,079,949
Patent Claims:	1. An isolated antibody, or antigen-binding fragment thereof, that: (a) binds to complement component human C5; (b) inhibits the cleavage of C5 into fragments C5a and C5b; (c) comprises: (i) a heavy chain CDR1 comprising the amino acid sequence depicted in SEQ ID NO:23, (ii) a heavy chain CDR2 comprising the amino acid sequence depicted in SEQ ID NO:19, (iii) a heavy chain CDR3 comprising the amino acid sequence depicted in SEQ ID NO:3, (iv) a light chain CDR1 comprising the amino acid sequence depicted in SEQ ID NO:4, (v) a light chain CDR2 comprising the amino acid sequence depicted in SEQ ID NO:5, and (vi) a light chain CDR3 comprising the amino acid sequence depicted in SEQ ID NO:6; and (d) comprises a variant human IgG Fc constant region that binds to human neonatal Fc receptor (FcRn), wherein the CH3 domain of the variant human Fc constant region comprises Met-429-Leu and Asn-435-Ser substitutions at residues corresponding to methionine 428 and Asparagine 434 of a native human IgG Fc constant region, each in EU numbering. 2. The isolated antibody, or antigen-binding fragment thereof, according to claim 1, comprising a heavy chain variable region depicted in SEQ ID NO:12 and a light chain variable region depicted in SEQ ID NO:8. 3. The isolated antibody, or antigen-binding fragment thereof, according to claim 1, further comprising a heavy chain constant region depicted in SEQ ID NO:13. 4. The isolated antibody, or antigen-binding fragment thereof, according to claim 1, comprising a heavy chain polypeptide comprising the amino acid sequence depicted in SEQ ID NO: 14 and a light chain polypeptide comprising the amino acid sequence depicted in SEQ ID NO: 11. 5. The isolated antibody, or antigen-binding fragment thereof, according to claim 1, wherein the antibody has a serum half-life in humans of at least 25 days. 6. The isolated antibody, or antigen-binding fragment thereof, according to claim 1, wherein the antibody or antigen-binding fragment thereof binds to human C5 at pH 7.4 and 25.degree. C. with an affinity dissociation constant (K.sub.D) that is in the range 0.1 nM.ltoreq.K.sub.D.ltoreq.1 nM. 7. The isolated antibody, or antigen-binding fragment thereof, according to claim 1, wherein the antibody or antigen-binding fragment thereof binds to human C5 at pH 6.0 and 25.degree. C. with a K.sub.D .gtoreq.10 nM. 8. The isolated antibody, or antigen-binding fragment thereof, according to claim 1, wherein the [(K.sub.D of the antibody or antigen-binding fragment thereof for human C5 at pH 6.0 and at 25.degree. C.)/(K.sub.D of the antibody or antigen-binding fragment thereof for human C5 at pH 7.4 and at 25.degree. C.)] is greater than 25. 9. An isolated antibody, or antigen-binding fragment thereof, that: (a) binds to complement component human C5; (b) inhibits the cleavage of human C5 into fragments C5a and C5b; and (c) comprises: (i) a heavy chain CDR1 comprising the amino acid sequence depicted in SEQ ID NO:23, (ii) a heavy chain CDR2 comprising the amino acid sequence depicted in SEQ ID NO:19, (iii) a heavy chain CDR3 comprising the amino acid sequence depicted in SEQ ID NO:3, (iv) a light chain CDR1 comprising the amino acid sequence depicted in SEQ ID NO:4, (v) a light chain CDR2 comprising the amino acid sequence depicted in SEQ ID NO:5, and (vi) a light chain CDR3 comprising the amino acid sequence depicted in SEQ ID NO:6, wherein the [(K.sub.D of the antibody or antigen-binding fragment thereof for human C5 at pH 6.0 and at 25.degree. C.)/(K.sub.D of the antibody or antigen-binding fragment thereof for human C5 at pH 7.4 and at 25.degree. C.)] is greater 24, wherein the antibody comprises a variant human IgG Fc constant region that binds to human neonatal Fc receptor (FcRn), wherein the CH3 domain of the variant human Fc constant region comprises Met-429-Leu and Asn-435-Ser substitutions at residues corresponding to methionine 428 and Asparagine 434 of a native human IgG Fc constant region, each in EU numbering, and wherein the antibody has a serum half-life in humans that is at least 25 days. 10. The isolated antibody, or antigen-binding fragment thereof, according to claim 9, wherein the antibody or antigen-binding fragment thereof comprises a heavy chain variable region polypeptide comprising the amino acid sequence depicted in SEQ ID NO: 12 and a light chain variable region comprising the amino acid sequence depicted in SEQ ID NO: 8. 11. The isolated antibody, or antigen-binding fragment thereof, according to claim 9, further comprising a heavy chain constant region depicted in SEQ ID NO:13. 12. An isolated antibody, or antigen-binding fragment thereof, that binds to complement component human C5, and comprises a heavy chain polypeptide comprising the amino acid sequence depicted in SEQ ID NO:14 and a light chain polypeptide comprising the amino acid sequence depicted in SEQ ID NO:11. 13. The isolated antibody or antigen binding fragment thereof of claim 12, wherein the antibody is manufactured in a CHO cell. 14. The isolated antibody or antigen binding fragment thereof of claim 13, wherein the antibody does not contain detectable sialic acid residues. 15. A pharmaceutical composition comprising a pharmaceutically-acceptable carrier and the antibody or antigen-binding fragment thereof according to claim 1. 16. A therapeutic kit comprising: (i) the isolated antibody or antigen-binding fragment according to claim 1 and (ii) instructions for administering the antibody or antigen-binding fragment to a human. 17. The therapeutic kit of claim 16, further comprising a syringe. 18. An article of manufacture comprising: a container comprising a label; and a composition comprising: (i) the isolated antibody or antigen-binding fragment according to claim 1, wherein the label indicates that the composition is to be administered to a human having, or suspected of having a complement-associated condition. 19. A pharmaceutical composition comprising a pharmaceutically-acceptable carrier and the antibody or antigen-binding fragment thereof according to claim 9. 20. A pharmaceutical composition comprising a pharmaceutically-acceptable carrier and the antibody or antigen-binding fragment thereof according to claim 12.

Details for Patent 9,079,949

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Alexion Pharmaceuticals, Inc.	ULTOMIRIS	ravulizumab-cwvz	Injection	761108	12/21/2018		2034-03-07
Alexion Pharmaceuticals, Inc.	ULTOMIRIS	ravulizumab-cwvz	Injection	761108	10/09/2020		2034-03-07

International Patent Family for US Patent 9,079,949

Country	Patent Number	Estimated Expiration
Argentina	099698
Australia	2015226977
Australia	2019236617