Columbia University

Jan K Kitajewski

Carrie Shawber

Yasuhiro Funahashi

Timothy C Wang

Thaned Kangsamaksin

Reyhaan Ali Chaudhri

Hendrik Uyttendaele

The invention provides for methods for treating an inflammatory disease of the digestive system in a subject by administering a trefoil family molecule. The invention provides for methods for treating a digestive system cancer in a subject by administering a trefoil family molecule. The invention provides for methods for cell proliferation in a subject by administering a trefoil family molecule.

Trefoil family factor proteins and uses thereof

This invention provides a fusion protein, the sequence of which, commencing at the N-terminus of the fusion protein, is identical to the sequence of amino acids in: Also provided is a composition comprising the any of the fusion proteins of this invention and a pharmaceutically acceptable carrier, a method of treating a subject suffering from age-related macular degeneration (AMD), diabetic retinopathy, or cancer which comprises administering to the subject any of the compositions of this invention in an amount effective to treat the subject's cancer.

Human Notch1 based fusion proteins as decoy inhibitors of jagged-notch signaling and DLL-notch signaling

Provided herein are Notch1 fusion proteins. These fusion proteins comprise consecutive amino acids the sequence of which, commencing at the N-terminus of the fusion protein, is identical to the sequence of the amino acids in an extracellular domain of a human Notch1 receptor protein and an Fc portion of an antibody. The amino acid sequence of the extracellular domain (ECD) of the human Notch1 receptor protein commences with the amino acid present at the N-terminus of EGF-like repeat 10 and extends at least through the C-terminal amino acid of EGF-like repeat 23. The N-terminal portion of the ECD of the human Notch1 receptor protein may extend up to the C-terminal amino acid of EGF-like repeat 24 or may extend up to the C-terminal amino acid of EGF-like repeat 36. Compositions of these fusion proteins are also provided. Also provided are methods of treating age-related macular degeneration (AMD), diabetic retinopathy and cancer using the fusion proteins described herein.

Human Notch1 decoys

Provided herein are Notch1 fusion proteins. These fusion proteins comprise consecutive amino acids the sequence of which, commencing at the N-terminus of the fusion protein, is identical to the sequence of the amino acids in an extracellular domain of a human Notch1 receptor protein and an Fc portion of an antibody. The amino acid sequence of the extracellular domain (ECD) of the human Notch1 receptor protein commences with the amino acid present at the N-terminus of BGF-like repeat 10 and extends at least through the C-terminal amino acid of EGF-like repeat 23. The N-terminal portion of the ECD of the human Notch1 receptor protein may extend up to the C-terminal amino acid of EGF-like repeat 24 or may extend up to the C-terminal amino acid of EGF-like repeat 36. Compositions of these fusion proteins are also provided. Also provided are methods of treating age-related macular degeneration (AND), diabetic retinopathy and cancer using the fusion proteins described herein.

This invention provides a fusion protein comprising a signal peptide, EGF repeats 1-X of the extracellular domain of human Notch3 receptor protein wherein X is any integer from 12 to 34, and an Fc portion of an antibody bound thereto. This invention also provides a method for treating a subject having a tumor, a method for inhibiting angiogenesis in a subject, a method for treating a subject having ovarian cancer, and a method for treating a subject having a metabolic disorder, comprising administering to the subject an amount of the above fusion protein effective to treat the subject. This invention further provides uses of the above fusion protein for the preparation of a pharmaceutical composition for the treatment of a subject having a tumor, for inhibiting angiogenesis in a subject, for treating a subject having ovarian cancer, and for treating a subject having a metabolic disorder.

Human Notch3 based fusion proteins as decoy inhibitors of Notch3 signaling

This invention provides a fusion protein comprising a single peptide, an extracellular domain of human Notch receptor protein and an Fc portion of an antibody bound thereto. This invention also provides a method for treating a subject having a tumor, a method for inhibiting angiogenesis in a subject, a method for treating a subject having ovarian cancer, and a method for treating a subject having a metabolic disorder, comprising administering to the subject an amount of the above fusion protein effective to treat the subject. This invention further provides uses of the above fusion protein for the preparation of a pharmaceutical composition for the treatment of a subject having a tumor, for inhibiting angiogenesis in a subject, for treating a subject having ovarian cancer, and for treating a subject having a metabolic disorder.

Compositions of humanized notch fusion proteins and methods of treatment

This invention provides a method for treating a subject having a tumor and a method for inhibiting angiogenesis in a subject, both comprising administering to the subject an effective amount of a composition of matter comprising the extracellular domain of a Notch receptor protein operably affixed to a half-life-increasing moiety. This invention also provides a composition of matter comprising the extracellular domain of Notch4 receptor protein operably affixed to a half-life-increasing moiety. This invention further provides an article of manufacture. Finally, this invention provides a replicable vector which encodes a polypeptide comprising the extracellular domain of a Notch receptor protein operably affixed to a half-life-increasing moiety, a host vector system which comprises such replicable vector and a method of producing such polypeptide.

Notch-based fusion proteins and uses thereof

This invention provides methods of modulating angiogenesis, including promoting or inhibiting angiogenesis, e.g., in connection with treating abnormalities including hemangiomas, hemangiosarcomas, Kaposi's Sarcoma, ischemic disorders, and wounds. These methods involve administration of compounds that are selective agonists or antagonists of Notch4 protein. In addition, this invention provides an isolated nucleic acid molecule encoding a Notch4, an isolated Notch4 protein, vectors comprising an isolated nucleic acid molecule encoding a Notch4 protein, cells comprising such vectors, antibodies directed to Notch4 protein, nucleic acid probes useful for detecting nucleic acids encoding Notch4 protein, and antisense oligonucleotides complementary to any unique sequences of a nucleic acid molecule which encodes Notch4 protein.

Growing community of inventors

Ridgewood, NJ, United States of America

Jan K Kitajewski