Anti-PD-1 antibodies and fusion proteins
AssigneeKadmon Corporation, LLC
InventorsDan Lu, Zhanna Polonskaya, Tzu-Pei Chang, Stella Aviaty Martomo, Jeegar P. Patel, Faical Miyara
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Abstract
Provided herein are recombinant antibodies, antigen-binding fragments, and fusion proteins thereof useful for binding to and inhibiting programmed death 1 (PD-1), nucleic acid molecules encoding the same and therapeutic compositions thereof, as well as methods of using such antibodies, including the methods for enhancing T cell and NK cell function to increase cell and cytokine mediated immunity and methods of treatment of various immune dysfunction related disorders including cancer and infectious diseases.
Claims19
A fusion protein comprising:
- (a) an anti-PD-1 antibody, wherein the sequences of CDR1H, CDR2H and CDR3H comprise SEQ ID NOS:
- 21, 22, and 23, and the sequences of CDR1L, CDR2L and CDR3L comprise SEQ ID NOS:
- 96, 97 and 82;
- (b) an IL-15Rα sushi domain polypeptide comprising the amino acid sequence of SEQ ID NO:
- 214, or an amino acid sequence that is at least 95% identical to SEQ ID NO:
- 214;
- (c) an IL-15 polypeptide comprising the amino acid sequence of SEQ ID NO:
- 212, or an amino acid sequence that is at least 90% identical to SEQ ID NO:
- 212;
- and
- (d) a first linker polypeptide joining the IL-15Rα sushi domain polypeptide and the IL-15 polypeptide;
- and further wherein:
- the IL-15Rα sushi domain polypeptide and the IL-15 polypeptide are fused to the N-terminus of the heavy chain variable region of the anti-PD-1 antibody, optionally by a second linker.
A fusion protein comprising (a) an anti-PD-1 antibody or antigen-binding fragment thereof, (b) an IL-15Rα sushi domain polypeptide, and (c) an IL-15 polypeptide, wherein the fusion protein comprises a light chain sequence comprising SEQ ID NO:
- 219 and a first heavy chain sequence comprising SEQ ID NO:
- 240 and a second heavy chain sequence comprising SEQ ID NO:
- 241.
Dependencies are inferred from the claim text.