US 8,133,982 B2Granted

FcγRIIB specific antibodies and methods of use thereof

AssigneeMacroGenics, Inc.

InventorsLeslie S. Johnson, Ling Huang

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Abstract

The present invention relates to humanized FcγRIIB antibodies, fragments, and variants thereof that bind human FcγRIIB with a greater affinity than said antibody binds FcγRIIA. The invention encompasses the use of the humanized antibodies of the invention for the treatment of any disease related to loss of balance of Fc receptor mediated signaling, such as cancer (preferably a B-cell malignancy, particularly, B-cell chronic lymphocytic leukemia or non-Hodgkin's lymphoma), autoimmune disease, inflammatory disease or IgE-mediated allergic disorder. The present invention also encompasses the use of a humanized FcγRIIB antibody or an antigen-binding fragment thereof, in combination with other cancer therapies. The invention provides methods of enhancing the therapeutic effect of therapeutic antibodies by administering the humanized antibodies of the invention to enhance the effector function of the therapeutic antibodies. The invention also provides methods of enhancing the efficacy of a vaccine composition by administering the humanized antibodies of the invention with a vaccine composition.

Claims13

Dependent claims

An immunoglobulin that comprises a humanized antibody or an antigen-binding fragment thereof that specifically binds to the extracellular domain of native human FcγRIIB with a greater affinity than said antibody binds to the extracellular domain of native human FcγRIIA, wherein the humanized antibody or antigen binding fragment thereof comprises a human framework region and:

(A) (1) a polypeptide comprising the amino acid sequence of SEQ ID NO. 1 (CDR1 of the heavy chain of humanized antibody 2B6), SEQ ID NO. 2 (CDR2 of the heavy chain of humanized antibody 2B6), and SEQ ID NO. 3 (CDR3 of the heavy chain of humanized antibody 2B6), and
(2) a polypeptide comprising the amino acid sequence of SEQ ID NO. 8 (CDR1 of the light chain of humanized antibody 2B6), SEQ ID NO. 11 (CDR2 of the light chain of humanized antibody 2B6), and SEQ ID NO. 12 (CDR3 of the light chain of humanized antibody 2B6), or
(B) (1) a polypeptide comprising the amino acid sequence of SEQ ID NO. 29 (CDR1 of the heavy chain of humanized antibody 3H7), SEQ ID NO. 30 (CDR2 of the heavy chain of humanized antibody 3H7), and SEQ ID NO. 31 (CDR3 of the heavy chain of humanized antibody 3H7), and
(2) a polypeptide comprising the amino acid sequence of SEQ ID NO. 38 (CDR1 of the light chain of humanized antibody 3H7), SEQ ID NO. 39 (CDR2 of the light chain of humanized antibody 3H7), and SEQ ID NO. 40 (CDR3 of the light chain of humanized antibody 3H7).

1 more element

Dependencies are inferred from the claim text.

Facts

Application: 12/349,876Filed 7 Jan 2009 · continuation
Priority: 10 May 2004
Published: US 2009/0202537 A113 Aug 2009
Granted: 13 Mar 2012
Term ends: Not estimatedThe source records don’t support an estimate.

Classification20 codes

C07K 16/283
Against the immunoglobulin superfamily: against Fc-receptors, e.g. CD16, CD32, CD64
A61P 1/04
Drugs for disorders of the alimentary tract or the digestive system: for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of…
A61P 7/00
Drugs for disorders of the blood or the extracellular fluid
A61P 11/02
Drugs for disorders of the respiratory system: nasal agents, e.g. decongestants

Family

Application60/569,882Us provisional application · filed 10 May 2004
Application60/582,043Us provisional application · filed 21 Jun 2004
Application11/126,978Parent of this continuation · filed 10 May 2005
US 7,521,542 B2Parent of this continuation · filed 21 Apr 2009
US 2009/0202537 A1Pre-grant publication · published 13 Aug 2009
US 2006/0013810 A1Published application
US 8,133,982 B2This patent

From the US filing history. Foreign family members aren’t listed.