Patents by Inventor Douglas B. Cines
Douglas B. Cines 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).
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Patent number: 11913963Abstract: The present invention provides a humanized antibody or antibody fragment comprising (a) a humanized light chain comprising 1) Complementarity Determining Region (CDR)-L1, the sequence of which is identical to the sequence of SEQ ID NO: 3; 2) CDR-L2, the sequence of which is identical to the sequence of SEQ ID NO: 4; and 3) CDR-L3, the sequence of which is identical to the sequence of SEQ ID NO: 5, and (b) a humanized heavy chain comprising 1) CDR-H1, the sequence of which is identical to the sequence of SEQ ID NO: 6; 2) CDR-H2, the sequence of which is identical to the sequence of SEQ ID NO: 7; and 3) CDR-H3, the sequence of which is identical to the sequence of SEQ ID NO: 8, as well as methods for treating, diagnosing, and monitoring the progression of HIT. The present invention also provides methods for assessing the antigenicity and ability to cause HIT of anionic anticoagulants.Type: GrantFiled: September 2, 2022Date of Patent: February 27, 2024Assignee: The Trustees of the University of PennsylvaniaInventors: Mark I. Greene, Douglas B. Cines, Zheng Cai, Zhiqiang Zhu
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Publication number: 20230265180Abstract: Provided herein are isolated antibodies or antibody fragments thereof that immunospecifically bind to platelet factor 4 (PF4). In some embodiments the isolated antibodies or antigen-binding fragments thereof comprise a light chain CDR and framework region comprising SEQ ID NO: 4 and a heavy chain CDR and framework region comprising SEQ ID NO: 10. Also provided herein are methods for treating heparin-induced thrombocytopenia (HIT) and methods for reducing the likelihood that subject will become afflicted with HIT. Further disclosed are uses of the isolated antibodies or antibody fragments in the treatment of HIT or the manufacture of compositions for the treatment of HIT.Type: ApplicationFiled: November 29, 2022Publication date: August 24, 2023Inventors: Mark I. GREENE, Zheng CAI, Zhiqiang ZHU, Douglas B. CINES
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Publication number: 20230160908Abstract: The present invention provides a humanized antibody or antibody fragment comprising (a) a humanized light chain comprising 1) Complementarity Determining Region (CDR)-L1, the sequence of which is identical to the sequence of SEQ ID NO: 3; 2) CDR-L2, the sequence of which is identical to the sequence of SEQ ID NO: 4; and 3) CDR-L3, the sequence of which is identical to the sequence of SEQ ID NO: 5, and (b) a humanized heavy chain comprising 1) CDR-H1, the sequence of which is identical to the sequence of SEQ ID NO: 6; 2) CDR-H2, the sequence of which is identical to the sequence of SEQ ID NO: 7; and 3) CDR-H3, the sequence of which is identical to the sequence of SEQ ID NO: 8, as well as methods for treating, diagnosing, and monitoring the progression of HIT. The present invention also provides methods for assessing the antigenicity and ability to cause HIT of anionic anticoagulants.Type: ApplicationFiled: September 2, 2022Publication date: May 25, 2023Inventors: Mark I. Greene, Douglas B. Cines, Zheng Cai, Zhiqiang Zhu
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Patent number: 11524999Abstract: Provided herein are isolated antibodies or antibody fragments thereof that immunospecifically bind to platelet factor 4 (PF4). In some embodiments the isolated antibodies or antigen-binding fragments thereof comprise a light chain CDR and framework region comprising SEQ ID NO: 4 and a heavy chain CDR and framework region comprising SEQ ID NO: 10. Also provided herein are methods for treating heparin-induced thrombocytopenia (HIT) and methods for reducing the likelihood that subject will become afflicted with HIT. Further disclosed are uses of the isolated antibodies or antibody fragments in the treatment of HIT or the manufacture of compositions for the treatment of HIT.Type: GrantFiled: May 11, 2018Date of Patent: December 13, 2022Assignee: The Trustees of the University of PennsylvaniaInventors: Mark I. Greene, Zheng Cai, Zhiqiang Zhu, Douglas B. Cines
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Patent number: 11435362Abstract: The present invention provides a humanized antibody or antibody fragment comprising (a) a humanized light chain comprising 1) Complementarity Determining Region (CDR)-L1, the sequence of which is identical to the sequence of SEQ ID NO: 3; 2) CDR-L2, the sequence of which is identical to the sequence of SEQ ID NO: 4; and 3) CDR-L3, the sequence of which is identical to the sequence of SEQ ID NO: 5, and (b) a humanized heavy chain comprising 1) CDR-H1, the sequence of which is identical to the sequence of SEQ ID NO: 6; 2) CDR-H2, the sequence of which is identical to the sequence of SEQ ID NO: 7; and 3) CDR-H3, the sequence of which is identical to the sequence of SEQ ID NO: 8, as well as methods for treating, diagnosing, and monitoring the progression of HIT. The present invention also provides methods for assessing the antigenicity and ability to cause HIT of anionic anticoagulants.Type: GrantFiled: June 20, 2019Date of Patent: September 6, 2022Assignee: The Trustees of the University of PennsylvaniaInventors: Mark I. Greene, Douglas B. Cines, Zheng Cai, Zhiqiang Zhu
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Publication number: 20200165333Abstract: Provided herein are isolated antibodies or antibody fragments thereof that immunospecifically bind to platelet factor 4 (PF4). In some embodiments the isolated antibodies or antigen-binding fragments thereof comprise a light chain CDR and framework region comprising SEQ ID NO: 4 and a heavy chain CDR and framework region comprising SEQ ID NO: 10. Also provided herein are methods for treating heparin-induced thrombocytopenia (HIT) and methods for reducing the likelihood that subject will become afflicted with HIT. Further disclosed are uses of the isolated antibodies or antibody fragments in the treatment of HIT or the manufacture of compositions for the treatment of HIT.Type: ApplicationFiled: May 11, 2018Publication date: May 28, 2020Inventors: Mark I. GREENE, Zheng CAI, Zhiqiang ZHU, Douglas B. CINES
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Publication number: 20200003786Abstract: The present invention provides a humanized antibody or antibody fragment comprising (a) a humanized light chain comprising 1) Complementarity Determining Region (CDR)-L1, the sequence of which is identical to the sequence of SEQ ID NO: 3; 2) CDR-L2, the sequence of which is identical to the sequence of SEQ ID NO: 4; and 3) CDR-L3, the sequence of which is identical to the sequence of SEQ ID NO: 5, and (b) a humanized heavy chain comprising 1) CDR-H1, the sequence of which is identical to the sequence of SEQ ID NO: 6; 2) CDR-H2, the sequence of which is identical to the sequence of SEQ ID NO: 7; and 3) CDR-H3, the sequence of which is identical to the sequence of SEQ ID NO: 8, as well as methods for treating, diagnosing, and monitoring the progression of HIT. The present invention also provides methods for assessing the antigenicity and ability to cause HIT of anionic anticoagulants.Type: ApplicationFiled: June 20, 2019Publication date: January 2, 2020Inventors: Mark I. Greene, Douglas B. Cines, Zheng Cai, Zhiqiang Zhu
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Patent number: 10371705Abstract: The present invention provides a humanized antibody or antibody fragment comprising (a) a humanized light chain comprising 1) Complementarity Determining Region (CDR)-L1, the sequence of which is identical to the sequence of SEQ ID NO: 3; 2) CDR-L2, the sequence of which is identical to the sequence of SEQ ID NO: 4; and 3) CDR-L3, the sequence of which is identical to the sequence of SEQ ID NO: 5, and (b) a humanized heavy chain comprising 1) CDR-H1, the sequence of which is identical to the sequence of SEQ ID NO: 6; 2) CDR-H2, the sequence of which is identical to the sequence of SEQ ID NO: 7; and 3) CDR-H3, the sequence of which is identical to the sequence of SEQ ID NO: 8, as well as methods for treating, diagnosing, and monitoring the progression of HIT. The present invention also provides methods for assessing the antigenicity and ability to cause HIT of anionic anticoagulants.Type: GrantFiled: November 5, 2015Date of Patent: August 6, 2019Assignee: The Trustees of the University of PennsylvaniaInventors: Mark I. Greene, Douglas B. Cines, Zheng Cai, Zhiqiang Zhu
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Publication number: 20180024140Abstract: The present invention provides a humanized antibody or antibody fragment comprising (a) a humanized light chain comprising 1) Complementarity Determining Region (CDR)-L1, the sequence of which is identical to the sequence of SEQ ID NO: 3; 2) CDR-L2, the sequence of which is identical to the sequence of SEQ ID NO: 4; and 3) CDR-L3, the sequence of which is identical to the sequence of SEQ ID NO: 5, and (b) a humanized heavy chain comprising 1) CDR-H1, the sequence of which is identical to the sequence of SEQ ID NO: 6; 2) CDR-H2, the sequence of which is identical to the sequence of SEQ ID NO: 7; and 3) CDR-H3, the sequence of which is identical to the sequence of SEQ ID NO: 8, as well as methods for treating, diagnosing, and monitoring the progression of HIT. The present invention also provides methods for assessing the antigenicity and ability to cause HIT of anionic anticoagulants.Type: ApplicationFiled: November 5, 2015Publication date: January 25, 2018Inventors: Mark I. GREENE, Douglas B. CINES, Zheng CAI, Zhiqlang ZHU
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Publication number: 20150132778Abstract: Provided herein are methods for diagnosing heparin-induced thrombocytopenia (HIT) in a subject. The methods comprise (a) contacting a PF4-heparin complex with a biological sample from the subject; (b) contacting the composition of part (a) with an HIT-like antibody; and (c) measuring the amount of bound HIT-like antibody. In one embodiment, a significant decrease in the amount of bound HIT-like antibody in the composition of part (b) as compared to a control level is indicative of a diagnosis of HIT in the subject. Also provided are assay kits for performing the methods of the invention.Type: ApplicationFiled: April 30, 2013Publication date: May 14, 2015Applicant: The Trustees of the University of PennsylvaniaInventors: Douglas B. Cines, Adam Cuker, Bruce Sachais
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Publication number: 20150037821Abstract: Methods and cells or cell lines for identifying antibodies or fragments thereof that activate heparin-induced thrombocytopenia (HIT) are described. The methods comprise contacting a hematopoietic cell or cell line that comprises, in operative association, the platelet receptor FcyRIIA under the control of a suitable promoter, and a reporter construct comprising a reporter gene under the control of a promoter and transcription factor, which transcription factor is regulated downstream of the signaling cascade of activated FcyRIIA, with a test sample from a mammalian subject; a platelet factor 4 (PF4), a wild-type or variant of PF4 or a fragment thereof; and heparin; and detecting or measuring the level of reporter gene expression.Type: ApplicationFiled: March 15, 2013Publication date: February 5, 2015Inventors: Steven P. Watson, Bruce Sachais, Douglas B. Cines
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Publication number: 20130058929Abstract: Fusion proteins containing a ligand which specifically binds to a selected vascular bed linked to an anti-thrombotic molecule are provided. Also provided are methods for use of these fusion proteins to prevent coagulation, to dissolve blood clots and to protect against the risk of iatrogenic side effects including those arising from cancer therapy and specific vascular occluding agents.Type: ApplicationFiled: June 20, 2012Publication date: March 7, 2013Applicant: The Trustees of the University of PennsylvaniaInventors: VLADIMIR R. MUZYKANTOV, Claudia Gottstein, Bi-Sen Ding, Douglas B. Cines
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Patent number: 8333973Abstract: Fusion proteins comprising a single chain antigen-binding domain (scFv) of a monoclonal antibody, linked to an anti-thrombotic agent, anti-inflammatory agent, or a pro-drug thereof are provided, where the polypeptide binds to a binding site (antigen) expressed on the surface of a red blood cell at a density greater than 5,000 copies per red blood cell. Pharmaceutical compositions comprising these fusion proteins, and methods of delivering an anti-thrombotic agent to the surface of a red blood cell via delivery of these fusion proteins, and methods of treating or preventing thrombosis, tissue ischemia, acute myocardial infarction (AMI), ischemic stroke, cerebrovascular disease, pulmonary embolism, or ischemic peripheral vascular disease via administration of the fusion proteins or compositions comprising same are also provided.Type: GrantFiled: December 31, 2008Date of Patent: December 18, 2012Assignee: The Trustees of the University of PennsylvaniaInventors: Vladimir R. Muzykantov, Sergei V. Zaitsev, Bi-Sen Ding, Douglas B. Cines
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Publication number: 20110262466Abstract: Compositions are provided comprising a thrombomodulin domain linked to a targeting moiety that binds to a determinant on the surface of a target endothelial cell or red blood cell, wherein the thrombomodulin domain may be the extracellular domain, the N-terminal lectin-like domain, or an epidermal growth factor (EGF)-like domain. The targeting moiety may be a single chain antigen-binding domain (scFv), and the targeting moiety and thrombomodulin domain of the composition may be linked as a continuous polypeptide chain. Methods of delivery and use of a composition described herein are provided, as well as methods of treating or preventing thrombosis, inflammation, tissue ischemia, sepsis, acute lung injury (ALI), acute myocardial infarction (AMI), ischemic stroke, cerebrovascular disease, pulmonary embolism, or ischemic peripheral vascular disease is provided.Type: ApplicationFiled: October 16, 2009Publication date: October 27, 2011Applicant: The Trustees of the University of PennsylvaniaInventors: Vladimir R. Muzykantov, Bi-Sen Ding, Douglas B. Cines, Claudia Gottstein, Steven M. Albelda
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Patent number: 7939063Abstract: Recombinant nucleic acid molecules are constructed with a first sequence encoding a transgene under the control of regulatory sequences that direct expression of the transgene product in a hematopoietic stem cell, or a progenitor cell therefrom or cell differentiated therefrom. In one embodiment, the cell which expresses the transgene is a secretory cell. The cell is a megakaryotic progenitor cell, or a cell further differentiated therefrom, such as a platelet. The cell is a granulocyte/macrophage progenitor cell or a cell further differentiated therefrom, such as a mast cell or neutrophils. Such host cells containing the molecule or the molecule itself are employed in methods for treating or preventing infection, inflammation or vascular injuries or any disorders involving or mediated by cells of the hematopoietic lineage.Type: GrantFiled: October 16, 2006Date of Patent: May 10, 2011Assignees: The Trustees of the University of Pennsylvania, The Children's Hospital of PhiladelphiaInventors: Douglas B. Cines, Mortimer Poncz
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Publication number: 20100285015Abstract: Fusion proteins comprising a single chain antigen-binding domain (scFv) of a monoclonal antibody, linked to an anti-thrombotic agent, anti-inflammatory agent, or a pro-drug thereof are provided, where the polypeptide binds to a binding site (antigen) expressed on the surface of a red blood cell at a density greater than 5,000 copies per red blood cell. Pharmaceutical compositions comprising these fusion proteins, and methods of delivering an anti-thrombotic agent to the surface of a red blood cell via delivery of these fusion proteins, and methods of treating or preventing thrombosis, tissue ischemia, acute myocardial infarction (AMI), ischemic stroke, cerebrovascular disease, pulmonary embolism, or ischemic peripheral vascular disease via administration of the fusion proteins or compositions comprising same are also provided.Type: ApplicationFiled: December 31, 2008Publication date: November 11, 2010Applicant: The Trustees of the University of PennsylvaniaInventors: Vladimir R. Muzykantov, Sergei V. Zaitsev, Bi-Sen Ding, Douglas B. Cines
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Publication number: 20090264628Abstract: Urokinase-type plasminogen activator (uPA) binds its cellular receptor (uPAR) with high affinity, thus localizing the generation of plasmin from plasminogen on the surface of a variety of cells. Disclosed herein is the structure of suPAR (uPAR1-277) complexed with the amino terminal fragment (ATF) of uPA (uPA1-143) at a resolution of 1.9 ú by X-ray crystallography. Three consecutive domains of uPAR (D1, D2 and D3) form the shape of a thick-walled teacup with a cone shape cavity in the middle, which has a wide opening (25 ú) and large depth (14 ú). uPA1-143 inserts into the cavity of uPAR and forms a large interface. The structure provides the basis for high affinity binding between uPA and uPAR and suggests the D1 and D2 domain of uPAR and the GFD domain of uPA (uPA7-43) are primarily responsible for uPA-uPAR binding. This structure presents the first high resolution view of uPA-uPAR interaction, and provides, among other things, a new platform for designing uPA-uPAR inhibitors/antagonists.Type: ApplicationFiled: October 3, 2006Publication date: October 22, 2009Applicants: Beth-Israel Deaconess Medical Center , Inc., Attenuon LLC, The University of PennsylvaniaInventors: Mingdong Huang, Qing Huai, Graham C. Parry, Douglas B. Cines, Andrew P. Mazar
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Publication number: 20090130104Abstract: Fusion proteins containing a ligand which specifically binds to a selected vascular bed linked to an anti-thrombotic molecule are provided. Also provided are methods for use of these fusion proteins to prevent coagulation, to dissolve blood clots and to protect against the risk of iatrogenic side effects including those arising from cancer therapy and specific vascular occluding agents.Type: ApplicationFiled: October 5, 2006Publication date: May 21, 2009Applicant: The Trustees of the University of PennsylvaniaInventors: Vladimir R. Muzykantov, Claudia Gottstein, Bi-Sen Ding, Douglas B. Cines
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Publication number: 20080317761Abstract: A pharmaceutical composition comprises a therapeutic peptide or protein, a transport moiety capable of transporting said first peptide or protein into a hematopoietic cell differentiated from a common myeloid progenitor, and a linker between said first protein and said transport moiety, said linker susceptible to cleavage by an intracellular enzyme in the cell. A cell or collection of cells, e.g., platelets, containing such a composition is useful in methods for treating infection, inflammation, vascular injuries or any disorders involving or mediated by cells of the hematopoietic lineage. Methods of making such compostions are also disclosed.Type: ApplicationFiled: April 28, 2005Publication date: December 25, 2008Applicants: The Trustees of the University of Pennsylvania, The Children's Hospital of PhiladelphiaInventors: Douglas B. Cines, Mortimer Poncz
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Patent number: 7425534Abstract: The present invention relates to compositions and methods comprising one or more domains of urokinase-type plasminogen activator (uPA) in an amount effective to modulate one or more of the contractility and angiogenic activity of a mammalian muscle or endothelial cell or tissue for use in the treatment of a disease or condition having as a symptom thereof one or more of abnormal muscle cell or tissue contractility and abnormal angiogenic activity. The one or more domains of uPA can be present in the inventive compositions and methods either as part of the full uPA molecule in either single chain or two chain form (scuPA or tcuPA), or as an isolated polypeptide, or a fragment of the uPA molecule (e.g., the amino terminal fragment “ATF”), or a deletion mutant of the uPA molecule.Type: GrantFiled: December 21, 2004Date of Patent: September 16, 2008Assignee: The Trustees of the University of PennsylvaniaInventors: Douglas B. Cines, Abd Al-Roof Higazi