Methods of inhibiting naive T-cell proliferation using anti-CD27 antibodies

Patent metadata

Field	Value
Publication number	US-10689453-B2
Application number	US-201916382645-A
Country	US
Kind code	B2
Filing date	Apr 12, 2019
Priority date	Mar 15, 2012
Publication date	Jun 23, 2020
Grant date	Jun 23, 2020

Abstract

Human antibodies immunospecific for human CD27 are capable of blocking CD27 binding to its ligand CD70 and neutralizing bioactivity of CD27 including, but not limited to, CD27 intracellular signaling, T-cell proliferation and activation, B-cell proliferation and differentiation, plasmablast formation and alleviation of antibody responses, stimulation of tumor cells by CD70, and the production of soluble mediators from T and B-cells. The antibodies are useful in diagnosing or treating CD27 activity associated diseases and conditions.

First claim

What is claimed:

1. A method of inhibiting naïve T-cell proliferation, comprising contacting a portion of human T-cells with an effective amount of a human CD27 antibody or antigen-binding fragment thereof comprising a light chain variable region and a heavy chain variable region, said light chain variable region comprising:
a complementarity determining region light chain 1 (CDRL1) amino acid sequence selected from the group consisting of SEQ ID NOs: 59-66 and 158;
a CDRL2 amino acid sequence selected from the group consisting of SEQ ID NOs: 67-74; and
a CDRL3 amino acid sequence of SEQ ID NO: 75;
said heavy chain variable region comprising:
a CDRH1 amino acid sequence selected from the group consisting of SEQ ID NOs: 42-45 and 161;
a CDRH2 amino acid sequence selected from the group consisting of SEQ ID NOs: 46-57, 156, and 157; and
a CDRH3 amino acid sequence of SEQ ID NO: 58, and the antibody or antigen binding portion thereof inhibits the activation of CD27 on said human T-cells in the presence of human CD70 protein.

2. The method of claim 1 , wherein the contacting step comprises contacting the T-cells with an effective amount of a human CD27 antibody or antigen-binding fragment thereof comprising a light chain variable region and a heavy chain variable region, said light chain variable region comprising:
a CDRL1 amino acid sequence of SEQ ID NO: 62;
a CDRL2 amino acid sequence of SEQ ID NO: 68; and
a CDRL3 amino acid sequence of SEQ ID NO: 75, and said heavy chain variable region comprising:

a CDRH1 amino acid sequence selected from the group consisting of SEQ ID NOs: 44 and 161;
a CDRH2 amino acid sequence of SEQ ID NO: 47; and
a CDRH3 amino acid sequence of SEQ ID NO: 58.

3. The method of claim 1 , wherein the contacting step comprises contacting the T-cells with an effective amount of a human CD27 antibody or antigen-binding fragment thereof comprising a light chain variable amino acid sequence of SEQ ID NO: 143 and a heavy chain variable amino acid sequence of SEQ ID NO: 133.

4. The method of claim 3 , wherein the antibody further comprises an IgG4 heavy chain constant region and an IgG4 light chain constant region.

5. The method of claim 4 , wherein the heavy chain constant region comprises the amino acid sequence of SEQ ID NO:159 and the light chain constant region comprises the amino acid sequence of SEQ ID NO:160.

Assignees

• Janssen Biotech Inc

Inventors

• Chen John
• Fransson Johan
• Fursov Natalie
• Hamel Damon
• Malia Thomas
• Obmolova Galina
• Ort Tatiana
• Rycyzyn Michael
• Scully Michael
• Sweet Raymond
• Teplyakov Alexey
• Wheeler John
• Almagro Juan Carlos

Classifications

• A61P27/02

  Ophthalmic agents · CPC title

• C07K2317/73

  Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation · CPC title

• C07K2317/76

  Antagonist effect on antigen, e.g. neutralization or inhibition of binding · CPC title

• C07K16/2878 Primary

  against the NGF-receptor/TNF-receptor superfamily, e.g. CD27, CD30, CD40, CD95 · CPC title

• C07K16/2896

  against molecules with a "CD"-designation, not provided for elsewhere · CPC title