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US 2026/0217831 A1Published application
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.
Claims21
-76. (canceled)
A fusion protein comprising:
- a) an anti-PD-1 antibody, wherein the antibody comprises a heavy chain variable region and a light chain variable region, wherein each of the heavy chain and the light chain variable regions comprise a CDR1, CDR2, and CDR3;
- 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;
- and
- c) an IL-15 polypeptide comprising an amino acid sequence that is at least 95% identical to SEQ ID NO:
- 212;
- d) a first linker polypeptide joining the IL-15Rα sushi domain polypeptide and the IL-15 polypeptide,
- wherein the anti-PD-1 antibody comprises a constant region, wherein the IL-15Rα sushi domain polypeptide and the IL-15 polypeptide are fused to the C-terminus of the constant region, and
- wherein the IL-15 polypeptide is a mutant IL-15 polypeptide comprising amino acid substitution N65A as numbered according to the mature human IL-15 sequence of SEQ ID NO:
- 212.
8 more elements
A fusion protein comprising:
- a) an anti-PD-1 antibody, wherein the antibody comprises a heavy chain variable region and a light chain variable region, wherein each of the heavy chain and the light chain variable regions comprise a CDR1, CDR2, and CDR3;
- 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;
- and
- c) an IL-15 polypeptide comprising an amino acid sequence that is at least 95% identical to SEQ ID NO:
- 212;
- d) a first linker polypeptide joining the IL-15Rα sushi domain polypeptide and the IL-15 polypeptide,
- wherein the anti-PD-1 antibody comprises a constant region, wherein the IL-15Rα sushi domain polypeptide and the IL-15 polypeptide are fused to the C-terminus of the constant region,
- wherein the anti-PD-1 antibody comprises a first and a second heavy chain, wherein the first heavy chain comprises an amino acid substitution selected from the group consisting of T350V, L351Y, S354C, S364H, T366Y, T366W, F405A and Y407V (Kabat EU index numbering), and the second heavy chain comprises an amino acid substitution selected from the group consisting of Y349C, T350V, T366L, T366S, L368A, K392L, T394W, Y407V and Y407T (Kabat EU index numbering),
- wherein the IL-15 polypeptide is a mutant IL-15 polypeptide comprising amino acid substitution N65A as numbered according to the mature human IL-15 sequence of SEQ ID NO:
- 212, and
- wherein the fusion protein comprises not more than one IL-15Rα sushi domain polypeptide and not more than one IL-15 polypeptide.
10 more elements
A fusion protein comprising:
- a) an anti-PD-1 antibody, wherein the antibody comprises a heavy chain variable region and a light chain variable region, wherein each of the heavy chain and the light chain variable regions comprise a CDR1, CDR2, and CDR3;
- 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;
- and
- c) an IL-15 polypeptide comprising an amino acid sequence that is at least 95% identical to SEQ ID NO:
- 212;
- d) a first linker polypeptide joining the IL-15Rα sushi domain polypeptide and the IL-15 polypeptide,
- wherein the anti-PD-1 antibody comprises a constant region, wherein the IL-15Rα sushi domain polypeptide and the IL-15 polypeptide are fused to the C-terminus of the constant region,
- wherein the anti-PD-1 antibody blocks binding of PD-L1 to PD-1,
- wherein the IL-15 polypeptide is a mutant IL-15 polypeptide comprising amino acid substitution N65A as numbered according to the mature human IL-15 sequence of SEQ ID NO:
- 212,
- wherein the IL-15 polypeptide has 10%-90% of the activity of human IL-15.
10 more elements
Dependencies are inferred from the claim text.