Macrogenics, Inc.

Other

Gurunadh Reddy Chichili

Leslie Sydnor Johnson

Paul A Moore

Ezio Bonvini

Ling Ling Huang

Kalpana Shah

Ralph Froman Alderson

Chia-Ying Kao Lam

Scott Koenig

Liqin Liu

Ross La Motte-Mohs

Bhaswati Barat

Stephen James Burke

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 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

Bispecific molecules having immunoreactivity with PD-1 and CTLA-4, 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 is directed to sequence-optimized CD 123&#xd7;CD3 bi-specific monovalent diabodies that are capable of simultaneous binding to CD 123 and CD3, and to the uses of such diabodies in the treatment of hematologic malignancies.

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Germantown, MD, United States of America

Gurunadh Reddy Chichili