Macrogenics, Inc.

Medimmune Limited

University of Texas System

Boehringer Ingelheim International Gmbh

Duke University

Other

The University of North Carolina at Chapel Hill

St. Jude Children's Research Hospital

Bowie State University

Pfizer Corporation

Medimmine, LLC

Virion Systems, Inc.

Immunogen, Inc.

Applied Molecular Evolution

Leslie Sydnor Johnson

Ling Ling Huang

Ezio Bonvini

Paul A Moore

Scott Koenig

Kalpana Shah

James F Young

Chia-Ying Kao Lam

Liqin Liu

William D Huse

Deryk T Loo

Nadine Tuaillon

Francine Zhifen Chen

Herren Wu

William Dall'Acqua

Jeffrey D Watkins

Ross La Motte-Mohs

Gurunadh Reddy Chichili

Sanjaya Singh

Rachel Rebecca Barrett

Barton F Haynes

Elizabeth Sally Ward

Theresa M Wizemann

Hua Watson Li

Guido Ferrari

Jonathan C Li

Jeffrey Lee Nordstrom

Douglas H Smith

John E Adamou

Gundo Diedrich

Bhaswati Barat

Jeffry Dean Watkins

Pankaj Gupta

Scott Ronald Brodeur

Ralph Froman Alderson

Sarah Low

Qi Pan

Elizabeth Sally Ward Ober

Robyn Gerena

Juniper A Scribner

Haixia Wu

Kathleen Last-Barney

Daw-Tsun Shih

Patricia Giblin

Nelamangala Nagaraja

Elaine I Tuomanen

H Robert Masure

David Margolis

Godfrey Jonah Anderson Rainey

Ronald L Wilder

Stephen James Burke

Julia A Sung

Thomas Son

Wei Chen

Bradford Braden

Godfrey Jonah Rainey

Lioudmila Tchistiakova

William Brady

Lidia Mosyak

Sergey Gorlatov

Radoslav P Kotorov

Laird Bloom

Adam Reid Root

Nicholas C Yoder

Chad Michael May

Laura Lerner

Herron Wu

Gregory Prince

Jon Heinrichs

Stuart William Hicks

William Dall'acqua

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 relates to CD3-binding molecules capable of binding to human and non-human CD3, and in particular to such molecules that are cross-reactive with CD3 of a non-human mammal (e.g., a cynomolgus monkey). The invention also pertains to uses of such antibodies and antigen-binding fragments in the treatment of cancer, autoimmune and/or inflammatory diseases and other conditions.

CD3-binding molecules capable of binding to human and non-human CD3

This invention relates to antibodies that specifically bind HER2/neu, and particularly chimeric 4D5 antibodies to HER2/neu, which have reduced glycosylation as compared to known 4D5 antibodies. The invention also relates to methods of using the 4D5 antibodies and compositions comprising them in the diagnosis, prognosis and therapy of diseases such as cancer, autoimmune diseases, inflammatory disorders, and infectious disease.

HER2/neu-specific antibodies and methods of using same

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 disclosure relates to compounds specific for IL23A and BAFF, compositions comprising the compounds, and methods of use thereof. Nucleic acids, cells, and methods of production related to the compounds and compositions are also disclosed.

Compound targeting IL-23A and B-cell activating factor (BAFF) 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

The present invention is directed to molecules (e.g., an antibody, a diabody, an scFv, an antibody, a TandAb, etc.) capable of binding an epitope of human CD16 (a 'CD16 Binding Molecule'). The present invention is further directed to CD 16 Binding Molecules that are capable of binding an epitope of human CD16 and one or more epitope(s) of a Disease Antigen ('DA') (e.g., a &#x201c;CD16&#xd7;DA Binding Molecule&#x201d;). The present invention is particularly directed to such CD16&#xd7;DA Binding Molecules that are antibodies, or that comprise an Epitope Binding Domain thereof, or are diabodies (including DART&#xae; diabodies), bispecific antibodies, TandAbs, other multispecific binding molecules (e.g., trivalent TRIDENT&#x2122; molecules), etc. The invention particularly concerns CD16&#xd7;DA Binding Molecules that are capable of binding a Disease Antigen that is a Cancer Antigen or a Pathogen-Associated Antigen in addition to being able to bind CD 16. The invention particularly concerns the use of such CD16 and CD16&#xd7;DA Binding Molecules in the treatment of cancer and pathogen-associated diseases. The present invention is also directed to pharmaceutical compositions that comprise such molecule(s).

Bispecific CD16-binding molecules and their use in the treatment of disease

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

The disclosure relates to compounds specific for IL23A and TNF-alpha, compositions comprising the compounds, and methods of use thereof. Nucleic acids, cells, and methods of production related to the compounds and compositions are also disclosed.

Compound targeting IL-23A and TNF-alpha and uses thereof

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 novel B7-H3-binding molecules capable of binding to human and non-human B7-H3, and in particular to such molecules that are cross-reactive with B7-H3 of a non-human primate (e.g., a cynomolgus monkey). The invention additionally pertains to B7-H3-binding molecules that comprise Variable Light Chain and/or Variable Heavy Chain (VH) Domains that have been humanized and/or deimmunized so as to exhibit a reduced immunogenicity upon administration to recipient subjects. The invention particularly pertains to bispecific, trispecific or multispecific B7-H3-binding molecules, including bispecific diabodies, BiTEs, bispecific antibodies, trivalent binding molecules, etc. that comprise: (i) such B7-H3-binding Variable Domains and (ii) a domain capable of binding to an epitope of a molecule present on the surface of an effector cell. The invention is also directed to pharmaceutical compositions that contain any of such B7-H3-binding molecules, and to methods involving the use of any of such B7-H3-binding molecules in the treatment of cancer and other diseases and conditions. The invention also particularly pertains to a molecule that comprises the human B7-H3 binding domain of a humanized anti-human B7-H3 antibody conjugated to at least one drug moiety (a 'B7-H3-ADC'). The invention is also directed to pharmaceutical compositions that contain such B7-H3-ADCs, and to methods involving the use of any of such B7-H3-ADCs in the treatment of cancer and other diseases and conditions.

B7-H3 directed antibody drug conjugates

Growing community of inventors

Darnestown, MD, United States of America

Leslie Sydnor Johnson