Human Genome Sciences, Inc.

Macrogenics, Inc.

Celera Corporation

Other

Pfizer Corporation

Paul A Moore

Steven M Ruben

Leslie Sydnor Johnson

Craig A Rosen

Ezio Bonvini

Kalpana Shah

Jian Ni

Ling Ling Huang

Reinhard Ebner

David W LaFleur

Henrik S Olsen

Yanggu Shi

Daniel R Soppet

Paul E Young

Kimberly A Florence

Scott Koenig

Francine Zhifen Chen

Gregory A Endress

Ying-Fei Wei

Deryk T Loo

Laurie A Brewer

George Komatsoulis

Ross La Motte-Mohs

Reiner L Gentz

Chia-Ying Kao Lam

Gurunadh Reddy Chichili

Patrick J Dillon

Roxanne Duan

Liqin Liu

Jun Zhang

Timothy A Coleman

Steve Ruben

D Roxanne Duan

Kenneth C Carter

Donna Mendrick

Pablo Jimenez

Joachim R Gruber

Mark A Rampy

Jonathan C Li

John M Greene

Charles E Birse

Douglas H Smith

Hla Kyaw

Michael Mucenski

Yi Li

Ann MeeJin Ferrie

Jing-Shan Hu

Tao He

David William Lafleur

Ralph Froman Alderson

Candy Lee

Zhizhen Zeng

Gundo Diedrich

Carrie L Fischer

Karen Van Orden

Guo-Liang Yu

Kevin P Baker

Ping Feng

Sudeepta Aggarwal

Ping Wei

Bhaswati Barat

Stephen James Burke

Michele Fiscella

Dong Fang

Wei Chen

Haodong Li

Lioudmila Tchistiakova

William A Haseltine

Gregg A Hastings

William Brady

Lidia Mosyak

Ping Fan

Joseph J Kenny

Elizabeth Joseloff

Mehdi Mesri

Charles Florence

Laird Bloom

Adam Reid Root

Henry Ji

Paul Richard Crocker

John R Hill

Chad Michael May

Daniel P Soppet

Daniel R Bednarik

Charles M Balash

Alexey Yevgenyevich Berezhnoy

Ding Liu

Jason B Bock

The present invention is directed to binding molecules that possess one or more epitope-binding sites specific for an epitope of CD137, including antibodies, and molecules comprising epitope-binding fragments thereof. The invention is further directed to multispecific binding molecules comprising one or more epitope-binding sites specific for an epitope of CD137 and one or more epitope-binding sites specific for an epitope of a tumor antigen ('TA') (e.g., a “CD137×TA Binding Molecule”). In one embodiment, such CD137×TA Binding Molecules will be bispecific molecules, especially bispecific tetravalent diabodies possessing two epitope-binding sites each specific for an epitope of CD137 and two epitope-binding sites each specific for an epitope of a TA. Alternatively, such CD137×TA Binding Molecules will be bispecific molecules possessing two epitope-binding sites each specific for an epitope of CD137 and one epitope-binding sites each specific for an epitope of a TA. The invention also provides novel Binding Molecules, as well as derivatives thereof and uses thereof. The invention is directed to pharmaceutical compositions that contain such CD137 molecules. The invention is additionally directed to methods for the use of such molecules in the treatment of cancer and other diseases and conditions.

CD137 binding molecules and uses thereof

The present invention is directed to binding molecules that possess one or more epitope-binding sites specific for an epitope of CD137 and one or more epitope-binding sites specific for an epitope of a tumor antigen ('TA') (e.g., a “CD137×TA Binding Molecule”). In one embodiment, such CD137×TA Binding Molecules will be bispecific molecules, especially bispecific tetravalent diabodies, that are composed of two, three, four or more than four polypeptide chains and possessing two epitope-binding sites each specific for an epitope of CD137 and two epitope-binding sites each specific for an epitope of a TA. Alternatively, such CD137×TA Binding Molecules will be bispecific molecules, especially bispecific trivalent binding molecules composed of three or more polypeptide chains and possessing one or two epitope-binding sites each specific for an epitope of CD137 and one or two epitope-binding sites each specific for an epitope of a TA. The CD137×TA Binding Molecules of the invention are capable of simultaneous binding to CD137, and a TA. The invention is directed to pharmaceutical compositions that contain any such CD137×TA Binding Molecules. The invention is additionally directed to methods for the use of such molecules in the treatment of cancer and other diseases and conditions. The invention also provides novel CD137-binding molecules, and HER2/neu-binding molecules, as well as derivatives thereof and uses thereof.

Bispecific binding molecules that are capable of binding CD137 and tumor antigens, and uses thereof

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 Tri-Specific Binding Molecules, which are multi-chain polypeptide molecules that possess three Binding Domains and are thus capable of mediating coordinated binding to three epitopes. The Binding Domains may be selected such that the Tri-Specific Binding Molecules are capable of binding to any three different epitopes. Such epitopes may be epitopes of the same antigen or epitopes of two or three different antigens. In a preferred embodiment, one of such epitopes will be capable of binding to CD3, the second of such epitopes will be capable of binding to CD8, and the third of such epitopes will be capable of binding to an epitope of a Disease-Associated Antigen. The invention also provides a novel ROR1-binding antibody, as well as derivatives thereof and uses for such compositions.

Multi-chain polypeptide-containing tri-specific binding molecules

Methods and compositions are provided for assessing, treating, and preventing diseases, especially cancer, using cancer-associated targets (CAT). Methods and compositions are also provided for determining or predicting the effectiveness of a treatment for these diseases or for selecting a treatment, using CAT. Methods and compositions are further provided for modulating cell function using CAT. Also provided are compositions that modulate CAT (e.g., antagonists or agonists), such as antibodies, proteins, small molecule compounds, and nucleic acid agents (e.g., RNAi and antisense agents), as well as pharmaceutical compositions thereof. Further provided are methods of screening for agents that modulate CAT, and agents identified by these screening methods.

Methods and compositions for diagnosing and treating diseases

The present invention relates to Tri-Specific Binding Molecules, which are multi-chain polypeptide molecules that possess three Binding Domains and are thus capable of mediating coordinated binding to three epitopes. The Tri-Specific Binding Molecule is preferably characterized in possessing binding domains that permit it to immunospecifically bind to: (1) an epitope of a first Cancer Antigen, (2) an epitope of a second Cancer Antigen, and (3) an epitope of a molecule that is expressed on the surface of an immune system effector cell, and are thus capable of localizing an immune system effector cell to a cell that expresses a Cancer Antigen, so as to thereby facilitate the killing of such cancer cell.

Tri-specific binding molecules that specifically bind to multiple cancer antigens

The present invention is directed to DA&#xd7;CD3 Binding Molecules comprising a vCD3-Binding Domain, which comprises a CDRHI Domain, a CDRH2 Domain, a CDRH3 Domain, a CDRL I Domain, a CDRL2 Domain, and a CDRL3 Domain, at least one of which differs in amino acid sequence from the amino acid sequence of the corresponding CDR of a rCD3-Binding Domain, wherein the DA&#xd7;CD3 Binding Molecule comprising such vCD3-Binding Domain exhibits an altered affinity for CD3, relative to a DA&#xd7;CD3 Binding Molecule comprising such rCD3-Binding Domain. The invention particularly concerns to such DA&#xd7;CD3 Binding Molecules comprising a vCD3-Binding Domain which exhibit reduced affinity for CD3 and are capable of mediating redirected killing of target cells expressing a DA and exhibit lower levels of cytokine release relative to a DA&#xd7;CD3 Binding Molecule comprising a rCD3-Binding Domain. The invention particularly concerns the use of DA&#xd7;CD3 Binding Molecules comprising a vCD3-Binding Domain in the treatment of cancer and pathogen-associated diseases. The present invention is also directed to pharmaceutical compositions that comprise such molecule(s).

Variant CD3-binding domains and their use in combination therapies for the treatment of disease

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 is directed to binding molecules that possess one or more epitope-binding sites specific for an epitope of CD137 and one or more epitope-binding sites specific for an epitope of a tumor antigen ('TA') (e.g., a 'CD137&#xd7;TA Binding Molecule'). In one embodiment, such CD137&#xd7;TA Binding Molecules will be bispecific molecules, especially bispecific tetravalent diabodies, that are composed of two, three, four or more than four polypeptide chains and possessing two epitope-binding sites each specific for an epitope of CD137 and two epitope-binding sites each specific for an epitope of a TA. Alternatively, such CD137&#xd7;TA Binding Molecules will be bispecific molecules, especially bispecific trivalent binding molecules composed of three or more polypeptide chains and possessing one or two epitope-binding sites each specific for an epitope of CD137 and one or two epitope-binding sites each specific for an epitope of a TA. The CD137&#xd7;TA Binding Molecules of the invention are capable of simultaneous binding to CD137, and a TA. The invention is directed to pharmaceutical compositions that contain any such CD137&#xd7;TA Binding Molecules. The invention is additionally directed to methods for the use of such molecules in the treatment of cancer and other diseases and conditions. The invention also provides novel CD137-binding molecules, and HER2/neu-binding molecules, as well as derivatives thereof and uses thereof.

The present invention is directed to bi-specific monovalent diabodies that comprise an immunoglobulin Fc Domain ('bi-specific monovalent Fc diabodies') and are composed of three polypeptide chains and which possess at least one binding site specific for an epitope of CD32B and one binding site specific for an epitope of CD79b (i.e., a 'CD32B&#xd7;CD79b bi-specific monovalent Fc diabody'). The bi-specific monovalent Fc diabodies of the present invention are capable of simultaneous binding to CD32B and CD79b. The invention is directed to such compositions, to pharmaceutical compositions that contain such bi-specific monovalent Fc diabodies and to methods for their use in the treatment of inflammatory diseases or conditions, and in particular, systemic lupus erythematosus (SLE) and graft vs. host disease.

Bi-specific monovalent Fc diabodies that are capable of binding CD32B and CD79b and uses thereof

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

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

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North Bethesda, MD, United States of America

Paul A Moore