Patents by Inventor Jennifer R. Cochran

Jennifer R. Cochran has filed for patents to protect the following inventions. This listing includes patent applications that are pending as well as patents that have already been granted by the United States Patent and Trademark Office (USPTO).

  • Patent number: 12024705
    Abstract: High-throughput methods for screening large populations of variant proteins are provided. The methods utilize large-scale arrays of microcapillaries, where each microcapillary comprises a solution containing a variant protein, an immobilized target molecule, and a reporter element. Immobilized target molecules may include any molecule of interest, including proteins, nucleic acids, carbohydrates, and other biomolecules. The association of a variant protein with a molecular target is assessed by measuring a signal from the reporter element. The contents of microcapillaries identified in the assays as containing variant proteins of interest can be isolated, and cells expressing the variant proteins of interest can be characterized. Also provided are systems for performing the disclosed screening methods.
    Type: Grant
    Filed: October 17, 2022
    Date of Patent: July 2, 2024
    Assignee: XCELLA Biosciences, Inc.
    Inventors: Jennifer R. Cochran, Bob Chen, Spencer Caleb Alford
  • Publication number: 20230227523
    Abstract: The present disclosure presents a general approach to engineering existing protein-protein interactions through domain addition and evolution. The disclosure teaches the creation of novel fusion proteins that include knottin peptides where a portion of the knottin peptide is replaced with a sequence that has been created for binding to a particular target. Such fusion proteins can also be bispecific or multi specific in that they can bind to and/or inhibit two or more receptors or receptor ligands. Knottins may be fused with an existing ligand (or receptor) as a general platform tor increasing the affinity of a ligand-receptor interaction or for creating a multi specific protein. In addition, the fusion proteins may comprise a knottin peptide fused to another protein where the other protein facilitates proper expression and folding of the knottin.
    Type: Application
    Filed: November 14, 2022
    Publication date: July 20, 2023
    Inventors: Jennifer R. Cochran, Douglas S. Jones, Mihalis S. Kariolis, Ping-Chuan Tsai
  • Publication number: 20230211001
    Abstract: Provided are bifunctional molecules that include a first moiety that specifically binds a cell surface molecule, and a second moiety that specifically binds a lysosomal targeting molecule. In certain embodiments, the first moiety is a knottin peptide comprising an engineered loop that binds to the cell surface molecule. The bifunctional molecules find use, e.g., for targeted degradation of cell surface molecules (e.g., proteins) via the endosomal/lysosomal pathway. Also provided are compositions and kits that include the bifunctional molecules, as well as methods of using the bifunctional molecules. Methods of making bifunctional molecules are also provided.
    Type: Application
    Filed: July 30, 2021
    Publication date: July 6, 2023
    Inventors: Green Ahn, Caitlyn Miller, Carolyn R. Bertozzi, Jennifer R. Cochran, Steven Banik
  • Publication number: 20230183676
    Abstract: High-throughput methods for screening large populations of variant proteins are provided. The methods utilize large-scale arrays of microcapillaries, where each microcapillary comprises a solution containing a variant protein, an immobilized target molecule, and a reporter element. Immobilized target molecules may include any molecule of interest, including proteins, nucleic acids, carbohydrates, and other biomolecules. The association of a variant protein with a molecular target is assessed by measuring a signal from the reporter element. The contents of microcapillaries identified in the assays as containing variant proteins of interest can be isolated, and cells expressing the variant proteins of interest can be characterized. Also provided are systems for performing the disclosed screening methods.
    Type: Application
    Filed: October 17, 2022
    Publication date: June 15, 2023
    Inventors: Jennifer R. Cochran, Bob Chen, Spencer Caleb Alford
  • Patent number: 11498952
    Abstract: The present disclosure presents a general approach to engineering existing protein-protein interactions through domain addition and evolution. The disclosure teaches the creation of novel fusion proteins that include knottin peptides where a portion of the knottin peptide is replaced with a sequence that has been created for binding to a particular target. Such fusion proteins can also be bispecific or multi specific in that they can bind to and/or inhibit two or more receptors or receptor ligands. Knottins may be fused with an existing ligand (or receptor) as a general platform tor increasing the affinity of a ligand-receptor interaction or for creating a multi specific protein. In addition, the fusion proteins may comprise a knottin peptide fused to another protein where the other protein facilitates proper expression and folding of the knottin.
    Type: Grant
    Filed: October 8, 2020
    Date of Patent: November 15, 2022
    Assignee: The Board of Trustees of the Leland Stanford Junior University
    Inventors: Jennifer R. Cochran, Douglas S. Jones, Mihalis S. Kariolis, Ping-Chuan Tsai
  • Publication number: 20220331401
    Abstract: Provided are methods of treating a KRAS mutant cancer in an individual. In certain embodiments, the methods include administering to an individual identified as having a KRAS mutant cancer a therapeutically effective amount of an agent that inhibits cardiotrophin-like cytokine factor 1 (CLCF1)-ciliary neurotrophic factor receptor (CNTFR) signaling. According to some embodiments, the KRAS mutant cancer is a KRAS mutant lung cancer, such as a KRAS mutant non-small cell lung cancer (NSCLC), e.g., a KRAS mutant lung adenocarcinoma (LUAD). Also provided are kits that find use, e.g., in practicing the methods of the present disclosure.
    Type: Application
    Filed: September 10, 2020
    Publication date: October 20, 2022
    Inventors: Eric Alejandro Sweet-Cordero, Jennifer R. Cochran, Jun Woo Kim, Cesar P. Marquez
  • Patent number: 11473081
    Abstract: High-throughput methods for screening large populations of variant proteins are provided. The methods utilize large-scale arrays of microcapillaries, where each microcapillary comprises a solution containing a variant protein, an immobilized target molecule, and a reporter element. Immobilized target molecules may include any molecule of interest, including proteins, nucleic acids, carbohydrates, and other biomolecules. The association of a variant protein with a molecular target is assessed by measuring a signal from the reporter element. The contents of microcapillaries identified in the assays as containing variant proteins of interest can be isolated, and cells expressing the variant proteins of interest can be characterized. Also provided are systems for performing the disclosed screening methods.
    Type: Grant
    Filed: December 11, 2017
    Date of Patent: October 18, 2022
    Assignee: XCELLA BIOSCIENCES, INC.
    Inventors: Jennifer R. Cochran, Bob Chen, Spencer Caleb Alford
  • Patent number: 11466063
    Abstract: Disclosed are knottin peptides containing non-natural amino acids so that they can be formed by chemical conjugation into two or more knottin monomers. The knottin monomers comprise a non-natural amino acid such as an aminooxy residue within the polypeptide sequence. The exemplified dimers were produced by oxime formation between two aldehyde groups present on a polyether linker and an aminooxy functional group that was site-specifically incorporated the knottin. Knottins variants based on EETI (Ecballium elaterium trypsin inhibitor) and AgRP (Agouti-related protein) were engineered to contain integrin-binding loops. These dimers were shown to have increased binding strength to integrins on U87MG tumor cells, achieving significant increases in inhibition of cell adhesion and proliferation. Also disclosed are knottin monomers comprising an aminooxy residue; these may be conjugated to molecules such as doxorubicin.
    Type: Grant
    Filed: September 9, 2019
    Date of Patent: October 11, 2022
    Assignee: The Board of Trustees of the Leland Stanford Junior University
    Inventors: Jennifer R. Cochran, Jun Woo Kim, Frank V. Cochran
  • Patent number: 11446356
    Abstract: Engineered peptides that bind with high affinity (low equilibrium dissociation constant (Kd)) to the cell surface receptors of fibronectin (?5?1) or vitronectin (?v?3 and ?v?5 integrins) are disclosed as useful as imaging tissue. These peptides are based on a molecular scaffold into which a subsequence containing the RGD integrin-binding motif has been inserted. The subsequence (RGD mimic) comprises about 9-13 amino acids, and the RGD contained within the subsequence can be flanked by a variety of amino acids, the sequence of which was determined by sequential rounds of selection (in vitro evolution). The molecular scaffold is preferably based on a knottin, e.g., EETI (Trypsin inhibitor 2 (Trypsin inhibitor II) (EETI-II) [Ecballium elaterium (Jumping cucumber)], AgRP (Agouti-related protein), and Agatoxin IVB, which peptides have a rigidly defined three-dimensional conformation. It is demonstrated that EETI tolerates mutations in other loops and that the present peptides may be used as imaging agents.
    Type: Grant
    Filed: February 28, 2020
    Date of Patent: September 20, 2022
    Assignee: The Board of Trustees of the Leland Stanford Junior University
    Inventors: Jennifer R. Cochran, Richard H. Kimura, Aron M. Levin
  • Publication number: 20220257785
    Abstract: Provided are conjugates comprising a knottin peptide comprising an engineered loop that binds to a cell surface molecule, and an immunostimulant conjugated to the knottin peptide via a linker. According to some embodiments, the immunostimulant activates a pathogen recognition receptor (PRR). For example, the immunostimulant may be a Toll-Like Receptor (TLR) agonist, e.g., an agonist of TLR 7, TLR 8 and/or TLR 9. Also provided are compositions (e.g., pharmaceutical compositions) that comprise the conjugates of the present disclosure, as well as kits comprising such compositions and methods of using such compositions, e.g., to treat an individual having cancer. Methods of making the conjugates of the present disclosure are also provided.
    Type: Application
    Filed: September 29, 2020
    Publication date: August 18, 2022
    Inventors: Idit Sagiv-Barfi, Ronald Levy, Caitlyn Miller, Jennifer R. Cochran, Carolyn R. Bertozzi
  • Publication number: 20220257729
    Abstract: The present invention provides a method of treating cancer with an integrin-binding-Fc fusion protein in combination with an SIRP?-CD47 immune checkpoint inhibitor, for example an anti-CD47 antibody or an anti-SIRP?-antibody. The invention also provides composition for use in such methods.
    Type: Application
    Filed: July 17, 2020
    Publication date: August 18, 2022
    Inventors: Jennifer R. Cochran, Amanda Lauren Rabe
  • Publication number: 20220249611
    Abstract: The present invention provides methods of screening for proteolytically stable growth factor variants, including, for example variants of human fibroblast growth factor 1 (FGF1). The present invention also provides for FGF1 variants comprising at least one amino acid substitution, an amino acid deletion, an amino acid addition and combinations thereof, wherein the resulting FGF1 variant exhibits increased proteolytic stability as compared to wild-type FGF1, as well as related uses.
    Type: Application
    Filed: October 9, 2019
    Publication date: August 11, 2022
    Inventors: Sung Jin Park, Jennifer R. Cochran
  • Publication number: 20220226435
    Abstract: Provided are ciliary neurotrophic factor receptor (CNTFR) ligands. In certain aspects, a CNTFR ligand of the present disclosure exhibits increased affinity for CNTFR relative to the corresponding wild-type CNTFR ligand. In certain aspects, a CNTFR ligand of the present disclosure results in reduced binding affinity of glycoprotein 130 (gp130), leukemia inhibitory factor receptor (LIFR), or both, for a complex including the CNTFR ligand and CNTFR, relative to the binding affinity for a complex including the corresponding wild-type CNTFR ligand and CNTFR. In certain aspects, a CNTFR ligand of the present disclosure has both of the aforementioned properties. Also provided are pharmaceutical compositions including the CNTFR ligands, as well as methods of using the CNTFR ligands.
    Type: Application
    Filed: November 19, 2021
    Publication date: July 21, 2022
    Inventors: Jun Woo Kim, Jennifer R. Cochran, Eric Alejandro Sweet-Cordero
  • Publication number: 20220220458
    Abstract: Compositions and methods are provided for alleviating cancer in a mammal by administering a therapeutic dose of a pharmaceutical composition that inhibits activity of AXL, MER or Tyro3 protein activity, for example by competitive or non-competitive inhibition of the binding interaction between AXL, MER or Tyro3 and its ligand GAS6.
    Type: Application
    Filed: September 2, 2021
    Publication date: July 14, 2022
    Inventors: Amato J. Giaccia, Erinn Bruno Rankin, Jennifer R. Cochran, Douglas Jones, Mihalis Kariolis, Katherine Cynthia Fuh, Yu Miao, Susan Hershenson
  • Publication number: 20220213171
    Abstract: Provided are agents that specifically bind a ligand of ciliary neurotrophic factor receptor (CNTFR). In certain aspects, an agent of the present disclosure is a soluble CNTFR polypeptide. The soluble CNTFR polypeptide may have an altered (e.g., reduced) binding affinity for one or more ligand-CNTFR complex subunits, an altered (e.g., increased) binding affinity for one or more CNTFR ligands, or any combination thereof. Compositions that include the agents of the present disclosure are also provided, as are methods of using the agents (e.g., for treating a cell proliferative disorder) and methods of identifying an individual as having a cell proliferative disorder associated with CNTFR signaling.
    Type: Application
    Filed: December 20, 2021
    Publication date: July 7, 2022
    Inventors: Jun Woo Kim, Jennifer R. Cochran, Eric Alejandro Sweet-Cordero
  • Publication number: 20220211861
    Abstract: Provided are conjugates. In certain aspects, provided are drug conjugates that include a knottin peptide comprising an engineered loop that binds to a cell surface molecule, and an anti-microtubule agent conjugated to the knottin peptide via a linker. In some aspects, provided are drug conjugates that include a fusion protein that includes a knottin peptide comprising an engineered loop that binds to a cell surface molecule, fused to an antibody subunit or fragment thereof. Such drug conjugates further include a drug conjugated to the fusion protein. Also provided are compositions and kits that include the conjugates of the present disclosure. Methods of using the conjugates, e.g., for therapeutic purposes, are also provided.
    Type: Application
    Filed: May 21, 2020
    Publication date: July 7, 2022
    Inventors: Jennifer R. Cochran, James R. Kintzing, Caitlyn Miller
  • Publication number: 20220193197
    Abstract: The present invention provides a method of treating cancer with a combination of IL-2 and an integrin-binding-Fc fusion protein. The methods of the invention can be applied to a broad range of cancer types.
    Type: Application
    Filed: August 19, 2021
    Publication date: June 23, 2022
    Inventors: Karl Dane WITTRUP, Jennifer R. COCHRAN, Byron Hua KWAN
  • Publication number: 20220184181
    Abstract: The present invention provides HGF polypeptide variants, including dimers, for use in treatment, in particular to treat ocular diseases and disorders.
    Type: Application
    Filed: April 27, 2020
    Publication date: June 16, 2022
    Inventor: Jennifer R. Cochran
  • Publication number: 20220033453
    Abstract: The NK1 fragment of hepatocyte growth factor (HGF) binds to and activates the Met receptor, a transmembrane receptor tyrosine kinase that plays a critical role in embryonic development and organ formation. The instant application discloses NK1 variant polypeptides which act as agonists or antagonists of HGF. Further disclosed are covalently linked NK1 variant polypeptides. Many of the disclosed variant polypeptides possess improved stability characteristics.
    Type: Application
    Filed: March 22, 2021
    Publication date: February 3, 2022
    Inventors: Jennifer R. Cochran, Douglas S. Jones, II, Ping-Chuan Tsai
  • Publication number: 20220023385
    Abstract: The present invention provides polypeptide variants for use in treatment, in particular variants of fibroblast growth factor (FGF) and variants of hepatocyte growth factor (HGF) for use in combination to treat corneal epithelial defects (PCEDs) and/or corneal neovascularization.
    Type: Application
    Filed: October 9, 2019
    Publication date: January 27, 2022
    Inventors: Jennifer R. COCHRAN, David Myung