US 11,447,557 B2Granted

Antibodies and methods of use thereof

AssigneesAgenus Inc., Memorial Sloan Kettering Cancer Center, Ludwig Institute for Cancer Research

InventorsNicholas S. Wilson, Jeremy D. Waight, Gerd Ritter, David Schaer, Daniel Hirschhorn-Cymerman, Taha Merghoub, Ekaterina V. Breous-Nystrom, Volker Seibert, Takemasa Tsuji, Olivier Léger, Dennis J. Underwood, Marc Van Dijk

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Abstract

The present disclosure provides multispecific (e.g., bispecific) antibodies that specifically bind to human GITR and/or human OX40 as well as compositions comprising such antibodies. In a specific aspect, the multispecific antibodies specifically bind to human GITR and OX40 and modulate GITR and/or OX40 activity, e.g., enhance, activate, or induce GITR and/or OX40 activity, or reduce, deactivate, or inhibit GITR and/or OX40 activity. The present disclosure also provides methods for treating disorders, such as cancer, by administering a multispecific antibody that specifically binds to human GITR and/or OX40 and modulates GITR and/or OX40 activity, e.g., enhances, activates, or induces GITR and/or OX40 activity. Also provided are methods for treating autoimmune or inflammatory diseases or disorders, by administering a multispecific antibody that specifically binds to human GITR and/or OX40 and modulates GITR and/or OX40 activity, e.g., reduces, deactivates, or inhibits GITR and/or OX40 activity.

Claims46

Dependent claims

A method of producing a multispecific antibody comprising a first antigen-binding region that specifically binds human OX40 and a second antigen-binding region that specifically binds human GITR, wherein:

(a) the first antigen-binding region comprises a first heavy chain comprising CDRs VH-CDR1, VH-CDR2, and VH-CDR3, and a first light chain comprising CDRs VL-CDR1, VL-CDR2, and VL-CDR3, wherein the first heavy chain comprises the VH-CDR1, VH-CDR2, and VH-CDR3 amino acid sequences of the VH amino acid sequence of SEQ ID NO:
54, and the first light chain comprises the VL-CDR1, VL-CDR2, and VL-CDR3 amino acid sequences of the VL amino acid sequence of SEQ ID NO:
55;
and
(b) the second antigen-binding region comprises a second heavy chain comprising CDRs VH-CDR1, VH-CDR2, and VH-CDR3, and a second light chain comprising CDRs VL-CDR1, VL-CDR2, and VL-CDR3, wherein the second heavy chain comprises the VH-CDR1, VH-CDR2, and VH-CDR3 amino acid sequences of the VH amino acid sequence of SEQ ID NO:
18, and the second light chain comprises the VL-CDR1, VL-CDR2, and VL-CDR3 amino acid sequences of the VL amino acid sequence of SEQ ID NO:
19,
the method comprising:
(c) culturing a first host cell comprising a first polynucleotide encoding the first heavy chain and a second polynucleotide encoding the first light chain under suitable conditions such that the first heavy chain and the first light chain are expressed, and the first antigen-binding region is produced;
(d) culturing a second host cell comprising a third polynucleotide encoding the second heavy chain and a fourth polynucleotide encoding the second light chain under suitable conditions such that second heavy chain and the second light chain are expressed, and the second antigen-binding region is produced;
and
(e) contacting the first and the second antigen-binding regions produced in steps (c) and (d), under suitable conditions so that the multispecific antibody is produced.

9 more elements

(a) the first antigen-binding region comprises a first heavy chain comprising CDRs VH-CDR1, VH-CDR2, and VH-CDR3, and a first light chain comprising CDRs VL-CDR1, VL-CDR2, and VL-CDR3, wherein the first heavy chain comprises the VH-CDR1, VH-CDR2, and VH-CDR3 amino acid sequences of the VH amino acid sequence of SEQ ID NO:
54, and the first light chain comprises the VL-CDR1, VL-CDR2, and VL-CDR3 amino acid sequences of the VL amino acid sequence of SEQ ID NO:
55;
and
(b) the second antigen-binding region comprises a second heavy chain comprising CDRs VH-CDR1, VH-CDR2, and VH-CDR3, and a second light chain comprising CDRs VL-CDR1, VL-CDR2, and VL-CDR3, wherein the second heavy chain comprises the VH-CDR1, VH-CDR2, and VH-CDR3 amino acid sequences of the VH amino acid sequence of SEQ ID NO:
18, and the second light chain comprises the VL-CDR1, VL-CDR2, and VL-CDR3 amino acid sequences of the VL amino acid sequence of SEQ ID NO:
19,
the method comprising culturing a host cell comprising a first polynucleotide encoding the first heavy chain, a second polynucleotide encoding the first light chain, a third polynucleotide encoding the second heavy chain, and a fourth polynucleotide encoding the second light chain, under suitable conditions such that the first heavy chain, the second heavy chain, the first light chain, and the second light chain are expressed, and the multispecific antibody is produced.

5 more elements

Dependencies are inferred from the claim text.

Facts

Application: 15/781,043Filed 2 Dec 2016 · us provisional application
Priority: 2 Dec 2015
Published: US 2020/0079861 A112 Mar 2020
Granted: 20 Sep 2022
Term ends: Not estimatedThe source records don’t support an estimate.

Classification21 codes

C07K 16/2878
Against receptors, cell surface antigens or cell surface determinants: against the NGF-receptor/TNF-receptor superfamily, e.g. CD27, CD30, CD40, CD95
A61K 39/3955
Against materials from animals: against proteinaceous materials, e.g. enzymes, hormones, lymphokines
A61K 45/06
Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00: mixtures of active ingredients without…
A61P 19/02
Drugs for skeletal disorders: for joint disorders, e.g. arthritis, arthrosis