Macrogenics, Inc.

Other

Hofstra University

Ling Ling Huang

Leslie Sydnor Johnson

Ezio Bonvini

Paul A Moore

Deryk T Loo

Nadine Tuaillon

Francine Zhifen Chen

Jeffrey B Stavenhagen

Christopher Rankin

Sergey Gorlatov

Sujata Vijh

Gurunadh Reddy Chichili

Kalpana Shah

Chia-Ying Kao Lam

Ralph Froman Alderson

Hua Watson Li

Bhaswati Barat

Robyn Gerena

Liqin Liu

Stephen James Burke

Juniper A Scribner

Thomas Son

Wei Chen

Thomas L Huang

Godfrey Jonah Anderson Rainey

Brandy Voyer

Michael Anthony Marino

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 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 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 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

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 diabody molecules and uses thereof in the treatment of a variety of diseases and disorders, including immunological disorders, infectious disease, intoxication and cancers. The diabody molecules of the invention comprise two polypeptide chains that associate to form at least two epitope binding sites, which may recognize the same or different epitopes on the same or differing antigens. Additionally, the antigens may be from the same or different molecules. The individual polypeptide chains of the diabody molecule may be covalently bound through non-peptide bond covalent bonds, such as, but not limited to, disulfide bonding of cysteine residues located within each polypeptide chain. In particular embodiments, the diabody molecules of the present invention further comprise an Fc region, which allows antibody-like functionality to engineered into the molecule.

Covalent diabodies and uses thereof

The present invention is directed to diabody molecules and uses thereof in the treatment of a variety of diseases and disorders, including immunological disorders, infectious disease, intoxication and cancers. The diabody molecules of the invention comprise two polypeptide chains that associate to form at least two epitope binding sites, which may recognize the same or different epitopes on the same or differing antigens. Additionally, the antigens may be from the same or different molecules. The individual polypeptide chains of the diabody molecule may be covalently bound through nonpeptide bond covalent bonds, such as, but not limited to, disulfide bonding of cysteine residues located within each polypeptide chain. In particular embodiments, the diabody molecules of the present invention further comprise an Fc region, which allows antibody like functionality to engineered into the molecule.

The present invention relates to antibodies or fragments thereof that specifically bind Fc&#x3b3;RIIB, particularly human Fc&#x3b3;RIIB, with greater affinity than the antibodies or fragments thereof bind Fc&#x3b3;RIIA, particularly human Fc&#x3b3;RIIA. The present invention also provides the use of an anti-Fc&#x3b3;RIIB antibody or an antigen-binding fragment thereof, as a single agent therapy for the treatment, prevention, management, or amelioration of a cancer, preferably a B-cell malignancy, particularly, B-cell chronic lymphocytic leukemia or non-Hodgkin's lymphoma, an autoimmune disorder, an inflammatory disorder, an IgE-mediated allergic disorder, or one or more symptoms thereof. The invention provides methods of enhancing the therapeutic effect of therapeutic antibodies by administering the antibodies of the invention to enhance the effector function of the therapeutic antibodies. The invention also provides methods of enhancing efficacy of a vaccine composition by administering the antibodies of the invention.

Fc&#x3b3;RIIB-specific antibodies and methods of use thereof

The present invention provides a method for detecting synthetic indole and indazole cannabinoids in a sample known or suspected to contain a synthetic indole or indazole cannabinoid in the absence of chromatography. A deuterated solvent is added to the solid sample, creating a suspension. The synthetic cannabinoid is detected in the suspension by analysis of the sample NMR spectrum. When one-dimensional proton NMR is used, detection of a first peak between 8.00 and 8.50 ppm and a second peak between 4.00 and 4.40 ppm, indicates the presence of a synthetic indole or indazole cannabinoid. When two-dimensional Correlation Spectroscopy (COSY) NMR is used, detection of a first spot between 6.50 and 9.00 ppm and a second spot between 1.50 and 4.50 ppm indicates the presence of a synthetic indole or indazole cannabinoid.

Nuclear magnetic resonance implemented synthetic indole and indazole cannabinoid detection, identification, and quantification

B7-H3 binding molecules, antibody drug conjugates thereof and methods of use thereof

The present invention is directed to sequence-optimized CD123&#xd7;CD3 bi-specific monovalent diabodies that are capable of simultaneous binding to CD123 and CD3, and to the uses of such diabodies in the treatment of hematologic malignancies.

Bi-specific monovalent diabodies that are capable of binding CD123 and CD3, and uses thereof

The present invention relates to antibodies that are immunoreactive to the mammalian, and more particularly, the human B7-H3 receptor and to uses thereof, particularly in the treatment of cancer and inflammation. The invention thus particularly concerns humanized B7-H3-reactive antibodies that are capable of mediating, and more preferably enhancing the activation of the immune system against cancer cells that are associated with a variety of human cancers.

Growing community of inventors

San Jose, CA, United States of America

Ling Ling Huang