ANTI-PCSK9 AND METHODS FOR TREATING LIPID AND CHOLESTEROL DISORDERS
First Claim
Patent Images
1. An isolated polypeptide comprising a member selected from the group consisting of(i) CDR-H1, CDR-H2 and CDR-H3 of the variable region the 11B5 heavy chain immunoglobulin which comprises the amino acid sequence of SEQ ID NO:
- 10;
(ii) CDR-H1, CDR-H2 and CDR-H3 of the variable region the 75B9 heavy chain immunoglobulin which comprises the amino acid sequence of SEQ ID NO;
18;
(iii) CDR-H1, CDR-H2 and CDR-H3 of the variable region the 77D10 heavy chain immunoglobulin which comprises the amino acid sequence of SEQ ID NO;
26;
(iv) CDR-H1, CDR-H2 and CDR-H3 of the variable region the 29C10 heavy chain immunoglobulin which comprises the amino acid sequence of SEQ ID NO;
34;
(v) CDR-H1, CDR-H2 and CDR-H3 of the variable region the 22D11 heavy chain immunoglobulin which comprises the amino acid sequence of SEQ ID NO;
42;
(vi) CDR-H1, CDR-H2 and CDR-H3 of the variable region the 1F11/1G11 heavy chain immunoglobulin which comprises the amino acid sequence of SEQ ID NO;
50;
(vii) CDR-L1, CDR-L2 and CDR-L3 of the variable region the 11B5 light chain immunoglobulin which comprises the amino acid sequence of SEQ ID NO;
14;
(viii) CDR-L1, CDR-L2 and CDR-L3 of the variable region the 7559 light chain immunoglobulin which comprises the amino acid sequence of SEQ ID NO;
22;
(ix) CDR-L1, CDR-L2 and CDR-L3 of the variable region the 77D10 light chain immunoglobulin which comprises the amino acid sequence of SEQ ID NO;
30;
(x) CDR-L1, CDR-L2 and CDR-L3 of the variable region the 29C10 light chain immunoglobulin which comprises the amino acid sequence of SEQ ID NO;
38;
(xi) CDR-L1, CDR-L2 and CDR-L3 of the variable region the 22D11 light chain immunoglobulin which comprises the amino acid sequence of SEQ ID NO;
46; and
(xii) CDR-L1, CDR-L2 and CDR-L3 of the variable region the 1F11/1G11 light chain immunoglobulin which comprises the amino acid sequence of SEQ ID NO;
54.
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Abstract
The present invention provides compositions and methods for treating disorders of cholesterol and lipid metabolism by administration of an anti-PCSK9 antibody or a peptide inhibitor of PCSK9.
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Citations
61 Claims
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1. An isolated polypeptide comprising a member selected from the group consisting of
(i) CDR-H1, CDR-H2 and CDR-H3 of the variable region the 11B5 heavy chain immunoglobulin which comprises the amino acid sequence of SEQ ID NO: - 10;
(ii) CDR-H1, CDR-H2 and CDR-H3 of the variable region the 75B9 heavy chain immunoglobulin which comprises the amino acid sequence of SEQ ID NO;
18;(iii) CDR-H1, CDR-H2 and CDR-H3 of the variable region the 77D10 heavy chain immunoglobulin which comprises the amino acid sequence of SEQ ID NO;
26;(iv) CDR-H1, CDR-H2 and CDR-H3 of the variable region the 29C10 heavy chain immunoglobulin which comprises the amino acid sequence of SEQ ID NO;
34;(v) CDR-H1, CDR-H2 and CDR-H3 of the variable region the 22D11 heavy chain immunoglobulin which comprises the amino acid sequence of SEQ ID NO;
42;(vi) CDR-H1, CDR-H2 and CDR-H3 of the variable region the 1F11/1G11 heavy chain immunoglobulin which comprises the amino acid sequence of SEQ ID NO;
50;(vii) CDR-L1, CDR-L2 and CDR-L3 of the variable region the 11B5 light chain immunoglobulin which comprises the amino acid sequence of SEQ ID NO;
14;(viii) CDR-L1, CDR-L2 and CDR-L3 of the variable region the 7559 light chain immunoglobulin which comprises the amino acid sequence of SEQ ID NO;
22;(ix) CDR-L1, CDR-L2 and CDR-L3 of the variable region the 77D10 light chain immunoglobulin which comprises the amino acid sequence of SEQ ID NO;
30;(x) CDR-L1, CDR-L2 and CDR-L3 of the variable region the 29C10 light chain immunoglobulin which comprises the amino acid sequence of SEQ ID NO;
38;(xi) CDR-L1, CDR-L2 and CDR-L3 of the variable region the 22D11 light chain immunoglobulin which comprises the amino acid sequence of SEQ ID NO;
46; and(xii) CDR-L1, CDR-L2 and CDR-L3 of the variable region the 1F11/1G11 light chain immunoglobulin which comprises the amino acid sequence of SEQ ID NO;
54. - View Dependent Claims (2, 6, 7, 8, 9, 10, 12, 13, 17, 18, 19, 20, 21, 22, 24, 25, 29, 30, 31, 32, 33, 34, 35, 36, 37, 40, 42, 44, 45, 46, 47, 48, 49, 56, 57, 58, 59, 60, 61)
- 10;
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3-5. -5. (canceled)
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11. (canceled)
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14-16. -16. (canceled)
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23. (canceled)
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26-28. -28. (canceled)
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38. An isolated polypeptide comprising an amino acid sequence comprising about 90% or more amino acid sequence similarity to a fragment of the human LDL receptor which fragment consists of amino acids beginning at about amino acid position 314 and ending at about amino acid position 355 of said receptor;
- wherein said polypeptide optionally comprises one or more properties selected from the group consisting of;
(i) binds to PCSK9; (ii) competes with LDL receptor or an anti-PCSK9 antibody or antigen-binding fragment thereof for binding to PCSK9; (iii) reduces total cholesterol level when administered to an animal; (iv) reduces low density lipoprotein cholesterol level when administered to an animal; (v) reduces apolipoprotein B level when administered to an animal; (vi) reduces total cholesterol/high density lipoprotein ratio when administered to an animal; and (vii) reduces low density lipoprotein/high density lipoprotein ratio when administered to an animal; or a pharmaceutical composition thereof comprising a pharmaceutically acceptable carrier. - View Dependent Claims (39)
- wherein said polypeptide optionally comprises one or more properties selected from the group consisting of;
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41. (canceled)
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43. (canceled)
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50-55. -55. (canceled)
Specification