US 2012/0231005 A1Published application

Ax1 and ax189 psck9 antagonists and variants

AssigneeMerck Sharp & Dohme Corp.

InventorsPeter Peizhi Luo, Kevin Caili Wang, Pingyu Zhong, Mark Hsieh, Yan Li, Xinwei Wang, Feng Dong, Andrei Golosov, Yan Ni, Weirong Wang, Laurence B. Peterson, Rose Cubbon

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Abstract

Antagonists of human proprotein convertase subtilisin-kexin type 9 (“PCSK9”) are disclosed. The disclosed antagonists are effective in the inhibition of PCSK9 function and, accordingly, present desirable antagonists for use in the treatment of conditions associated with PCSK9 activity. The present invention also discloses nucleic acid encoding said antagonists, vectors, host cells, and compositions comprising the antagonists. Methods of making PCSK9-specific antagonists as well as methods of using the antagonists for inhibiting or antagonizing PCSK9 function are also disclosed and form important additional aspects of the present disclosure.

Claims24

Dependent claims

An isolated PCSK9-specific antagonist which comprises:

(a) a heavy chain variable region comprising CDR1, CDR2 and CDR3 sequence, wherein
(i) the CDR1 sequence is selected from the group consisting of:
SEQ ID NOs:
1, 2, 4, 6, 169 and residues 4-13 of SEQ ID NOs:
1, 2 and 6;
(ii) the CDR2 sequence is selected from the group consisting of:
SEQ ID NOs:
8, 9, 11, 13, 171 and residues 4-20 of SEQ ID NOs:
8, 9 and 13;
and
(iii) the CDR3 sequence is selected from the group consisting of SEQ ID NOs:
15, 16, 18, 20, 173 and residues 4-15 of SEQ ID NOs:
15, 16 and 20 and/or
(b) a light chain variable region comprising CDR1, CDR2 and CDR3 sequence, wherein
(i) the CDR1 sequence is selected from the group consisting of SEQ ID NOs:
22-24, 26 and 28;
(ii) the CDR2 sequence is selected from the group consisting of:
SEQ ID NOs:
30 and 31;
and
(iii) the CDR3 sequence is selected from the group consisting of:
SEQ ID NOs:
33-35, 37 and 39;
said antagonist which inhibits human PCSK9-dependent inhibition of cellular LDL uptake by at least 10%.

21 more elements

Dependencies are inferred from the claim text.