Macrogenics, Inc.

Medimmune Limited

Duke University

Other

The University of North Carolina at Chapel Hill

St. Jude Children's Research Hospital

The University of British Columbia

Applied Molecular Evolution

Koenig, Scott

Conroy, David

Scott Koenig

Leslie Sydnor Johnson

Ezio Bonvini

Paul A Moore

James F Young

Kalpana Shah

Ross La Motte-Mohs

Maria Concetta Veri

William D Huse

Chia-Ying Kao Lam

Liqin Liu

Jeffrey D Watkins

Herren Wu

Barton F Haynes

Jeffrey B Stavenhagen

Theresa M Wizemann

Guido Ferrari

Jeffrey Lee Nordstrom

Nadine Tuaillon

Douglas H Smith

Elaine I Tuomanen

David Conroy

Jon Marc Wigginton

H Robert Masure

Gurunadh Reddy Chichili

David Margolis

John E Adamou

Ronald L Wilder

Julia A Sung

Leslie S Johnson

Jeffry Dean Watkins

Solomon Langermann

John Smit

Nilofer Qureshi

Naimish Bharat Pandya

Jon Heinrichs

Robert Joseph Lechleider

James Vasselli

Maria-Concetta Veri

Stanley Pillemer

The invention is directed to bispecific molecules comprising an HIV-1 envelope targeting arm and an arm targeting an effector cell, compositions comprising these bispecific molecule and methods of use. In certain aspects, the bispecific molecules of the present invention can bind to two different targets or epitopes on two different cells within the first epitope is expressed on a different cell type than the second epitope, such that the bispecific molecules can bring the two cells together. In certain aspects, the bispecific molecules of the present invention can bind to two different cells, wherein the bispecific molecules comprises an arm with the binding specificity of A32, 7B2, CH27, CH28 or CH44.

Bispecific molecules comprising an HIV-1 envelope targeting arm

The present invention is directed to the anti-LAG-3 antibodies: LAG-3 mAb 1, LAG-3 mAb 2, LAG-3 mAb 4, LAG-3 mAb 5, and LAG-3 mAb 6, and to humanized and chimeric versions of such antibodies. The invention additionally pertains to LAG-3-binding molecules that comprise LAG-3 binding fragments of such anti-LAG-3 antibodies, immunoconjugates, and to bispecific molecules, including diabodies, BiTEs, bispecific antibodies, etc., that comprise (i) such LAG-3-binding fragments, and (ii) a domain capable of binding an epitope of a molecule involved in regulating an immune check point present on the surface of an immune cell. The present invention also pertains to methods of detecting LAG-3, as well as methods of using molecules that bind LAG-3 for stimulating immune responses.

LAG-3-binding molecules and methods of use thereof

The present invention is directed to bispecific molecules (e.g., diabodies, bispecific antibodies, trivalent binding molecules, etc.) that possess at least one epitope-binding site that is immunospecific for an epitope of PD-1 and at least one epitope-binding site that is immunospecific for an epitope of CTLA-4 (i.e., a 'PD-1&#xd7;CTLA-4 bispecific molecule'). The PD-1&#xd7;CTLA-4 bispecific molecules of the present invention are capable of simultaneously binding to PD-1 and to CTLA-4, particularly as such molecules are arrayed on the surfaces of human cells. The invention is directed to pharmaceutical compositions that contain such PD-1&#xd7;CTLA-4 bispecific molecules, and to methods involving the use of such bispecific molecules in the treatment of cancer and other diseases and conditions. The present invention also pertains to methods of using such PD-1&#xd7;CTLA-4 bispecific molecules to stimulate an immune response.

Methods of using bispecific molecules having immunoreactivity with PD-1 and CTLA-4

The present invention relates to methods of treating or preventing cancer and other diseases using molecules, particularly polypeptides, more particularly immunoglobulins (e.g., antibodies), comprising a variant Fc region, wherein said variant Fc region comprises at least one amino acid modification relative to a wild-type Fc region, which variant Fc region binds an Fc&#x3b3;R that activates a cellular effector ('Fc&#x3b3;R,' such as Fc&#x3b3;RIIA or Fc&#x3b3;RIIIA) and an Fc&#x3b3;R that inhibits a cellular effector ('Fc&#x3b3;R,' such as Fc&#x3b3;RIIA) with an altered Ratio of Affinities relative to the respective binding affinities of such Fc&#x3b3;R for the Fc region of the wild-type immunoglobulin. The methods of the invention are particularly useful in preventing, treating, or ameliorating one or more symptoms associated with a disease, disorder, or infection where either an enhanced efficacy of effector cell function mediated by Fc&#x3b3;R is desired (e.g., cancer, infectious disease) or an inhibited effector cell response mediated by Fc&#x3b3;R is desired (e.g., inflammation, autoimmune disease).

Methods for the treatment of disease using immunoglobulins having fc regions with altered affinities for FcgammaRactivating and FegammaRinhibiting

CD19&#xd7;CD3 bi-specific monovalent diabodies, and particularly, CD19&#xd7;CD3 bi-specific monovalent Fc diabodies, are capable of simultaneous binding to CD19 and CD3, and are used in the treatment of hematologic malignancies.

Bi-specific monovalent diabodies that are capable of binding CD19 and CD3, and uses thereof

The present invention is directed to selected anti-PD-1 antibodies capable of binding to both cynomolgus monkey PD-1 and to human PD-1: PD-1 mAb 1, PD-1 mAb 2, PD-1 mAb 3, PD-1 mAb 4, PD-1 mAb 5, PD-1 mAb 6, PD-1 mAb 7, PD-1 mAb 8, PD-1 mAb 9, PD-1 mAb 10, PD-1 mAb 11, PD-1 mAb 12, PD-1 mAb 13, PD-1 mAb 14, or PD-1 mAb 15, and to humanized and chimeric versions of such antibodies. The invention additionally pertains to PD-1-binding molecules that comprise PD-1 binding fragments of such anti-PD-1 antibodies, immunocongugates, and to bispecific molecules, including diabodies, BiTEs, bispecific antibodies, etc., that comprise (i) such PD-1-binding fragments, and (ii) a domain capable of binding an epitope of a molecule involved in regulating an immune check point present on the surface of an immune cells. The present invention also pertains to methods of using molecules that bind PD-1 for stimulating immune responses, as well as methods of detecting PD-1.

PD-1-binding molecules and methods of use thereof

The present invention relates to bispecific molecules that are capable of localizing an immune effector cell that expresses an activating receptor to a virally infected cell, so as to thereby facilitate the killing of the virally infected cell. In a preferred embodiment, such localization is accomplished using bispecific molecules that are immunoreactive with an activating receptor of an immune effector cell and to an antigen expressed by a cell infected with a virus wherein the antigen is detectably present on the cell infected with the virus at a level that is greater than the level at which the antigen is detected on the virus by the bispecific molecules, and to the use of such bispecific molecules in the treatment of latent viral infections.

Bispecific molecules that are immunoreactive with immune effector cells that express an activating receptor and an antigen expressed by a cell infected by a virus and uses thereof

The present invention is directed to a combination therapy involving the administration of a first molecule that specifically binds to human B7-H3 and a second molecule that specifically binds to human PD-1 to a subject for the treatment of cancer and/or inflammation. The invention also concerns pharmaceutical compositions that comprise a first molecule that specifically binds to human B7-H3 and a second molecule that specifically binds to human PD-1 that are capable of mediating, and more preferably enhancing, the activation of the immune system against cancer cells that are associated with any of a variety of human cancers. The invention also relates to the use of such pharmaceutical compositions to treat cancer and other diseases in recipient subjects.

Combination therapy for the treatment of cancer

The present invention is directed to bi-specific diabodies that comprise two or more polypeptide chains and which possess at least one Epitope-Binding Site that is immunospecific for an epitope of PD-1 and at least one Epitope-Binding Site that is immunospecific for an epitope of LAG-3 (i.e., a 'PD-1&#xd7;LAG-3 bi-specific diabody'). More preferably, the present invention is directed to bi-specific diabodies that comprise four polypeptide chains and which possess two Epitope-Binding Sites that are immunospecific for one (or two) epitope(s) of PD-1 and two Epitope-Binding Site that are immunospecific for one (or two) epitope(s) of LAG-3 (i.e., a 'PD-1&#xd7;LAG-3 bi-specific, tetra-valent diabody'). The present invention also is directed to such diabodies that additionally comprise an immunoglobulin Fc Domain (&#x201c;bi-specific Fc diabodies and bi-specific, tetra-valent, Fc diabodies&#x201d;). The diabodies of the present invention are capable of simultaneously binding to PD-1 and to LAG-3, particularly as such molecules are arrayed on the surfaces of human cells. The invention is directed to pharmaceutical compositions that contain such diabodies, and to methods involving the use of such diabodies in the treatment of cancer and other diseases and conditions.

Covalently bonded diabodies having immunoreactivity with PD-1 and LAG-3, and methods of use thereof

This invention relates to a pharmaceutical composition that comprises a first molecule that specifically binds HER2/neu and a second molecule that specifically binds a cell-surface receptor (or its ligand) that is involved in regulating an immune checkpoint (or the ligand thereof). The invention particularly relates to the embodiment wherein the second molecule binds to PD-1. The invention also relates to the use of such pharmaceutical compositions to treat cancer and other diseases.

The present invention is directed to the anti-LAG-3 antibodies, LAG-3 mAb 1, LAG-3 mAb 2, LAG-3 mAb 4, LAG-3 mAb 5, and LAG-3 mAb 6, and to humanized and chimeric versions of such antibodies. The invention additionally pertains to LAG-3-binding molecules that comprise LAG-3 binding fragments of such anti-LAG-3 antibodies, immunocongugates, and to bispecific molecules, including diabodies, BiTEs, bispecific antibodies, etc., that comprise (i) such LAG-3-binding fragments, and (ii) a domain capable of binding an epitope of a molecule involved in regulating an immune check point present on the surface of an immune cells. The present invention also pertains to methods of detecting LAG-3, as well as methods of using molecules that bind LAG-3 for stimulating immune responses.

Bispecific molecules having immunoreactivity with PD-1 and CTLA-4, and methods of use thereof

The invention is directed to bispecific molecules comprising an HIV-1 envelope targeting arm and an arm targeting an effector cell, compositions comprising these bispecific molecules and methods of use. In certain aspects, the bispecific molecules of the present invention can bind to two different targets or epitopes on two different cells wherein the first epitope is expressed on a different cell type than the second epitope, such that the bispecific molecules can bring the two cells together. In certain aspects, the bispecific molecules of the present invention can bind to two different cells, wherein the bispecific molecules comprises an arm with the binding specificity of A32, 7B2, CH27, CH28, or CH44.

Methods for the treatment of disease using immunoglobulins having Fc regions with altered affinities for Fc&#x3b3;Rand Fc&#x3b3;R

Growing community of inventors

Rockville, MD, United States of America

Scott Koenig