Claims for Patent: 9,803,007

Summary for Patent: 9,803,007

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), Wang; Yi (Woodbridge, CT)
Assignee:	Alexion Pharmaceuticals, Inc. (New Haven, CT)
Application Number:	15/492,622
Patent Claims:	1. A method for treating paroxysmal nocturnal hemoglobinuria (PNH), the method comprising administering to the subject an antibody, or antigen-binding fragment, thereof in an amount effective to treat the C5 mediated complement-associated condition, wherein the antibody, or antigen-binding fragment thereof, binds to complement component human C5, inhibits the cleavage of C5 into fragments C5a and C5b, has a serum half-life in humans of at least 40 days, and comprises: (i) a heavy chain CDR1 comprising the amino acid sequence depicted in SEQ ID NO:23, a heavy chain CDR2 comprising the amino acid sequence depicted in SEQ ID NO:19, a heavy chain CDR3 comprising the amino acid sequence depicted in SEQ ID NO:3, a light chain CDR1 comprising the amino acid sequence depicted in SEQ ID NO:4, a light chain CDR2 comprising the amino acid sequence depicted in SEQ ID NO:5, and a light chain CDR3 comprising the amino acid sequence depicted in SEQ ID NO:6; and (ii) 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 method of claim 1, wherein the antibody, or antigen-binding fragment thereof, comprises 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 method of claim 1, wherein the antibody, or antigen-binding fragment thereof, further comprises a heavy chain constant region depicted in SEQ ID NO:13. 4. The method of claim 1, wherein the antibody, or antigen-binding fragment thereof, 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. 5. The method of claim 1, wherein the isolated 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. 6. The method of 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. 7. The method of 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.

Details for Patent 9,803,007

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 9,803,007

Country	Patent Number	Estimated Expiration
Argentina	099698
Australia	2015226977
Australia	2019236617
Australia	2020267324