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Combination of Anti-PD-1 Antibodies and Anti-CD20/Anti-CD3 Antibodies to Treat Cancer

a technology of anti-cd20/anti-cd3 and anti-pd-1, which is applied in the field of cancer treatment, can solve the problems of less than 50% chance of relapse-free survival, poor prognosis of aggressive lymphomas, and not all patients respond, so as to inhibit the growth of cancer, improve the treatment effect, and improve the symptom or indication of at least one symptom

Inactive Publication Date: 2017-06-22
REGENERON PHARM INC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

The present invention provides methods for treating cancer or tumors in a subject by administering a therapeutically effective amount of an anti-PD-1 antibody and a bispecific antibody that specifically binds to CD20 and CD3. The methods involve sequentially administering one or more doses of the anti-PD-1 antibody and the bispecific antibody to the subject. The methods can be used to treat heme cell tumors or malignancies, such as Hodgkin's lymphoma, non-Hodgkin's lymphoma, follicular lymphoma, small lymphocytic lymphoma, lymphomatoid granulomatoid, acute lymphoblastic leukemia, hairy cell leukemia, and B cell chronic lymphocytic leukemia. The methods can also be used to prevent tumor recurrence or growth. The methods involve administering the anti-PD-1 antibody and the bispecific antibody either simultaneously or sequentially, and the dosages and treatment duration can vary depending on the specific cancer or tumor being treated.

Problems solved by technology

Although anti-CD20 tumor targeting strategies have shown great promise in clinical settings, not all patients respond to anti-CD20 therapy, and some patients have been shown to develop resistance to or exhibit incomplete responses to anti-CD20 therapy (e.g., partial depletion of peripheral B-cells), for reasons that are not well understood (but which typically do not include loss of CD20 expression).
Many patients with aggressive lymphomas have poor prognosis and less than 50% chance of relapse-free survival.
In addition, high-dose chemotherapy leads to severe adverse side effects.

Method used

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  • Combination of Anti-PD-1 Antibodies and Anti-CD20/Anti-CD3 Antibodies to Treat Cancer
  • Combination of Anti-PD-1 Antibodies and Anti-CD20/Anti-CD3 Antibodies to Treat Cancer
  • Combination of Anti-PD-1 Antibodies and Anti-CD20/Anti-CD3 Antibodies to Treat Cancer

Examples

Experimental program
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Effect test

example 1

fficacy of Anti-PD-1 Antibody in Combination with Anti-CD20×CD3 Bispecific Antibody Against B16_CD20 Tumors

[0098]In this Example, the effect of PD-1 blockade in combination with CD20-targeted immunotherapy was examined against established B16_CD20 tumors in mice humanized for CD20 and CD3 using anti-mouse PD-1 and anti-human CD20×CD3 bispecific antibodies.

[0099]The exemplary bispecific anti-CD20 / anti-CD3 antibody used in the Examples herein is “bsAb1” (also known as “Antibody 1” as disclosed in US20150266966), a fully human bispecific monoclonal antibody against CD20 and CD3 wherein the antibody comprises an anti-CD20 binding arm comprising a first heavy chain variable region (A-HCVR) comprising the amino acid sequence of SEQ ID NO: 11 and a light chain variable region (LCVR) comprising the amino acid sequence of SEQ ID NO: 12; and an anti-CD3 binding arm comprising a second heavy chain variable region (B-HCVR) comprising the amino acid sequence of SEQ ID NO: 13 and a LCVR comprisin...

example 2

fficacy of Anti-PD-1 Antibody and Anti-CD20×CD3 Bispecific Antibody Using a Sequential Dosing Regimen

[0105]In this Example, the anti-tumor effect of anti-mouse PD-1 antibody in combination with anti-human CD20×CD3 bispecific antibody was examined using a sequential dosing regimen.

[0106]Double humanized CD20 CD3 mice were engineered using VelociGene® technology (Valenzuela et al 2003, Nat. Biotechnol. 21: 652-659; U.S. patent application Ser. No. 14 / 949,834, filed on Nov. 23, 2015).

[0107]Mice were subcutaneously implanted with 2.5×105 B16_CD20 cells on day −7. On day 0, thirty-five mice with tumor volumes between 30 and 65 mm3 were selected and randomized into seven treatment groups (FIG. 2). Tumor growth was measured by calipers and body weights recorded twice a week for the entire length of the study. Mice were treated twice a week intraperitoneally with antibodies as follows: Group 1: control (PBS); Group 2: Isotype controls (a bivalent human antibody against an irrelevant antigen...

example 3

Trial of Anti-PD-1 Antibody and Anti-CD20×CD3 Antibody in Patients with B-Cell Malignancies

[0109]This study is an open-label, multicenter, dose escalation study with multiple dose escalation and expansion arms to investigate the efficacy, safety, and tolerability of anti-PD-1 antibody and anti-CD20 / anti-CD3 bispecific antibody, alone and in combination, in adult patients with B-cell malignancies (including B-cell non-Hodgkin lymphoma, Hodgkin's lymphoma, and acute lymphoblastic leukemia).

[0110]The exemplary anti-PD-1 antibody used in this Example is REGN2810 (also known as H4H7798N as disclosed in US20150203579), a fully human monoclonal anti-PD-1 antibody comprising a heavy chain comprising the amino acid sequence of SEQ ID NO: 9 and a light chain comprising the amino acid sequence of SEQ ID NO: 10; an HCVR / LCVR amino acid sequence pair comprising SEQ ID NOs: 1 / 2; and heavy and light chain CDR sequences comprising SEQ ID NOs: 3-8.

[0111]The exemplary bispecific anti-CD20 / anti-CD3 an...

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Abstract

The present invention provides methods for treating, reducing the severity, or inhibiting the growth of cancer (e.g., a B-cell cancer such as Hodgkin's lymphoma or acute lymphoblastic leukemia). The methods of the present invention comprise administering to a subject in need thereof a therapeutically effective amount of an antibody or antigen-binding fragment thereof that specifically binds to programmed death 1 (PD-1) receptor in combination with a therapeutically effective amount of a bispecific antibody that specifically binds to CD20 and CD3.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS[0001]This application claims the benefit under 35 USC §119(e) of U.S. provisional application No. 62 / 270,749, filed Dec. 22, 2015, which is herein specifically incorporated by reference in its entirety.FIELD OF THE INVENTION[0002]The present invention relates to methods for treating cancer comprising administering to a subject in need thereof a therapeutically effective amount of an antibody that specifically binds to programmed death 1 (PD-1) receptor in combination with a bispecific antibody that binds to CD20 and CD3.BACKGROUND[0003]B-cell cancers are a group of heterogeneous cancers of the white blood cells known as B-lymphocytes and include leukemias (located in the blood) and lymphomas (located in the lymph nodes). B-cell lymphomas include, but are not limited to, non-Hodgkin's lymphoma (NHL), and Hodgkin's lymphoma (HL). Lymphomas are divided into indolent (slow-growing) or aggressive lymphomas. A common indolent lymphoma is follicular ...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): C07K16/28A61K45/06A61K39/395C07K16/30
CPCC07K16/2887C07K16/2818C07K16/2809C07K16/3061A61K2039/505A61K39/3955C07K2317/31C07K2317/565A61K45/06A61P35/00A61P35/02A61P43/00
Inventor VARGHESE, BINDUTHURSTON, GAVINLOWY, ISRAELBROWNSTEIN, CARRIE
Owner REGENERON PHARM INC
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