Patents by Inventor Ira H. Pastan
Ira H. Pastan 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: 9492564Abstract: We tested the in vitro and in vivo efficacy of a recombinant bispecific immunotoxin that recognizes both EGFRwt and tumor-specific EGFRvIII receptors. A single chain antibody was cloned from a hybridoma and fused to toxin, carrying a C-terminal peptide which increases retention within cells. The binding affinity and specificity of the recombinant bispecific immunotoxin for the EGFRwt and the EGFRvIII proteins was measured. In vitro cytotoxicity was measured. In vivo activity of the recombinant bispecific immunotoxin was evaluated in subcutaneous models and compared to that of an established monospecific immunotoxin. In our preclinical studies, the bispecific recombinant immunotoxin, exhibited significant potential for treating brain tumors.Type: GrantFiled: May 6, 2014Date of Patent: November 15, 2016Assignees: Duke University, The United States of America, as represented by the Secretary of Health and Human Services, National Institutes of HealthInventors: Darell Bigner, Chien-Tsun Kuan, Ira H. Pastan, Charles Peagram
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Publication number: 20160272730Abstract: High affinity antibodies were made to gangliosides expressed on tumor cells. The antibodies can be used analytically, diagnostically, therapeutically, and theranostically. The antibodies may be used to target cytotoxic reagents to tumor cells, thus minimizing full-body toxicity. The antibodies may also be used with out added cytotoxin. The antibodies may be detectably labeled or labelable for analytic and diagnostic purposes. The combination of specificity and affinity of the antibodies render them particularly useful.Type: ApplicationFiled: June 2, 2016Publication date: September 22, 2016Applicants: Duke University, THE GOVERNMENT OF THE UNITED STATES AS REPRESENTED BY THE SECRETARY OF HEALTHInventors: Darell Bigner, Chien-Tsun Kuan, Ira H. Pastan, Hailan Piao
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Patent number: 9441048Abstract: High affinity antibodies were made to gangliosides expressed on tumor cells. The antibodies can be used analytically, diagnostically, therapeutically, and theranostically. The antibodies may be used to target cytotoxic reagents to tumor cells, thus minimizing full-body toxicity. The antibodies may also be used with out added cytotoxin. The antibodies may be detectably labeled or labelable for analytic and diagnostic purposes. The combination of specificity and affinity of the antibodies render them particularly useful.Type: GrantFiled: November 15, 2011Date of Patent: September 13, 2016Assignees: The United States of America as represented by the Secretary of Health and Human Services, Duke UniversityInventors: Darell Bigner, Chien-Tsun Kuan, Ira H. Pastan, Hailan Piao
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Patent number: 9416190Abstract: Described herein is the use of phage display antibody engineering technology and synthetic peptide screening to identify SD1 and SD2, human single-domain antibodies to mesothelin. SD1 recognizes a conformational epitope at the C-terminal end (residues 539-588) of human mesothelin close to the cell surface. SD2 binds full-length mesothelin. To investigate SD1 as a potential therapeutic agent, a recombinant human Fc (SD1-hFc) fusion protein was generated. The SD1-hFc protein exhibits strong complement-dependent cytotoxicity (CDC), in addition to antibody-dependent cellular cytotoxicity (ADCC), against mesothelin-expressing tumor cells. Furthermore, the SD1-hFc protein causes significant tumor growth inhibition of tumor xenografts in nude mice. SD1 and SD2 are the first human single-domain antibodies targeting mesothelin-expressing tumors.Type: GrantFiled: September 16, 2013Date of Patent: August 16, 2016Assignee: The United States of America, as represented by the Secretary, Department of Health and Human ServicesInventors: Mitchell Ho, Ira H. Pastan, Dimiter S. Dimitrov, Zhewei Tang, Mingqian Feng, Wei Gao
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Publication number: 20160229919Abstract: Described herein is the use of rabbit hybridoma technology, along with a panel of truncated mesothelin domain fragments, to identify anti-mesothelin mAbs that bind specific regions of mesothelin. In one aspect of the present disclosure, the rabbit mAbs bind an epitope that is not part of Region I. In particular, the identified mAbs (YP187, YP223, YP218 and YP3) bind either Region II (391-486), Region III (487-581) or a native conformation of mesothelin with subnanomolar affinity. These antibodies do not compete for binding with the mesothelin-specific immunotoxin SS1P or mesothelin-specific antibody MORAb-009. In another aspect, disclosed is a high-affinity rabbit mAb that binds Region I of mesothelin (YP158). YP158 binds native mesothelin protein in cancer cells and tissues with high affinity and specificity.Type: ApplicationFiled: April 28, 2016Publication date: August 11, 2016Applicant: The U.S.A., as represented by the Secretary, Department of Health and Human ServicesInventors: Mitchell Ho, Ira H. Pastan, Yen T. Phung, Yifan Zhang, Wei Gao, Raffit Hassan
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Patent number: 9409992Abstract: Described herein is the use of rabbit hybridoma technology, along with a panel of truncated mesothelin domain fragments, to identify anti-mesothelin mAbs that bind specific regions of mesothelin. In one aspect of the present disclosure, the rabbit mAbs bind an epitope that is not part of Region I. In particular, the identified mAbs (YP187, YP223, YP218 and YP3) bind either Region II (391-486), Region III (487-581) or a native conformation of mesothelin with subnanomolar affinity. These antibodies do not compete for binding with the mesothelin-specific immunotoxin SS1P or mesothelin-specific antibody MORAb-009. In another aspect, disclosed is a high-affinity rabbit mAb that binds Region I of mesothelin (YP158). YP158 binds native mesothelin protein in cancer cells and tissues with high affinity and specificity.Type: GrantFiled: August 16, 2013Date of Patent: August 9, 2016Assignee: The United States of America, as represented by the Secretary, Department of Health and Human ServicesInventors: Mitchell Ho, Ira H. Pastan, Yen T. Phung, Yifan Zhang, Wei Gao, Raffit Hassan
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Publication number: 20160215025Abstract: The invention provides a Pseudomonas exotoxin A (PE) comprising an amino acid sequence having a substitution of one or more B-cell and/or T-cell epitopes. The invention further provides related chimeric molecules, as well as related nucleic acids, recombinant expression vectors, host cells, populations of cells, and pharmaceutical compositions. Methods of treating or preventing cancer in a mammal, methods of inhibiting the growth of a target cell, methods of producing the PE, and methods of producing the chimeric molecule are further provided by the invention.Type: ApplicationFiled: April 11, 2016Publication date: July 28, 2016Applicant: The United States of America, as represented by the Secretary, Department of Health and Human ServInventors: Ira H. Pastan, Ronit Mazor, Masanori Onda, Aaron Vassall, Richard Beers, Jaime Eberle, Wenhai Liu
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Patent number: 9394352Abstract: POTE has recently been identified as a tumor antigen expressed in a variety of human cancers, including colon, ovarian, breast, prostate, lung and pancreatic cancer. Described herein are immunogenic POTE polypeptides, including modified POTE polypeptides, that bind MHC class I molecules. The immunogenic POTE polypeptides are capable of inducing an immune response against POTE-expressing tumor cells. Thus, provided herein is a method of eliciting an immune response in a subject, such as a subject having a type of cancer that expresses POTE.Type: GrantFiled: September 25, 2014Date of Patent: July 19, 2016Assignee: The United States of America, as represented by the Secretary, Department of Health and Human ServicesInventors: Jay A. Berzofsky, Yi-Hsiang Huang, Masaki Terabe, Ira H. Pastan
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Patent number: 9388222Abstract: The invention provides a Pseudomonas exotoxin A (PE) comprising an amino acid sequence having a substitution of one or more B-cell and/or T-cell epitopes. The invention further provides related chimeric molecules, as well as related nucleic acids, recombinant expression vectors, host cells, populations of cells, and pharmaceutical compositions. Methods of treating or preventing cancer in a mammal, methods of inhibiting the growth of a target cell, methods of producing the PE, and methods of producing the chimeric molecule are further provided by the invention.Type: GrantFiled: October 3, 2014Date of Patent: July 12, 2016Assignees: The United States of America, as represented by the Secretary, Department of Health and Human Services, Hoffman-La Roche Inc.Inventors: Ira H. Pastan, Ronit Mazor, Masanori Onda, Byungkook Lee, Gerhard Niederfellner, Sabine Imhof-Jung, Ulrich Brinkmann, Guy Georges
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Publication number: 20160168263Abstract: We have constructed a polynucleotide encoding a bispecific antibody engaging molecule which has one arm that specifically engages a tumor cell which expresses the human EGFRvIII mutant protein on its surface, and a second arm that specifically engages T cell activation ligand CD3. The polynucleotide is codon optimized for expression in CHO cells. The subunits of the engaging molecules are organized to achieve greater efficiency. These are promising therapeutic agents.Type: ApplicationFiled: July 9, 2014Publication date: June 16, 2016Applicants: DUKE UNIVERSITY, THE GOVERNMENT OF THE U.S. AS REPRESENTED BY THE SECRETARY OF HEALTHInventors: Darell D. Bigner, John Sampson, Chien-Tsun Kuan, Mingqing Cai, Bryan D. Choi, Patrick C. Gedeon, Ira H. Pastan
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Patent number: 9359447Abstract: The invention provides a chimeric antigen receptor (CAR) (a) an antigen binding domain of HN1 or SS, a transmembrane domain, and an intracellular T cell signaling domain, or (b) an antigen binding domain of SS1, a transmembrane domain, an intracellular T cell signaling domain, and a granulocyte-macrophage colony-stimulating factor (GM-CSF) receptor 2 leader. Nucleic acids, recombinant expression vectors, host cells, populations of cells, antibodies, or antigen binding portions thereof, and pharmaceutical compositions relating to the CARs are disclosed. Methods of detecting the presence of cancer in a mammal and methods of treating or preventing cancer in a mammal are also disclosed.Type: GrantFiled: March 5, 2013Date of Patent: June 7, 2016Assignee: The United States of America, as represented by the Secretary, Department of Health and Human ServicesInventors: Steven A. Feldman, Steven A. Rosenberg, Ira H. Pastan
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Publication number: 20160145338Abstract: Disclosed herein are isolated human monoclonal antibodies that specifically bind human CD22 with a dissociation constant (Kd) of 25 nM or less. Nucleic acids encoding these antibodies, expression vectors including these nucleic acid molecules, and isolated host cells that express the nucleic acid molecules are also disclosed. The antibodies can be used to detect human CD22 in a sample. In some cases, CD22 is soluble CD22. Methods of diagnosing a B-cell malignancy, or confirming a B-cell malignancy diagnosis, are disclosed herein that utilize these antibodies. Methods of treating a subject with a B-cell malignancy are also disclosed.Type: ApplicationFiled: February 1, 2016Publication date: May 26, 2016Applicant: The Government of the United States of America as represented by the Secretary of the Department ofInventors: Dimiter S. Dimitrov, Xiaodong Xiao, Ira H. Pastan
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Patent number: 9346859Abstract: The invention provides a Pseudomonas exotoxin A (PE) comprising an amino acid sequence having a substitution of one or more B-cell and/or T-cell epitopes. The invention further provides related chimeric molecules, as well as related nucleic acids, recombinant expression vectors, host cells, populations of cells, and pharmaceutical compositions. Methods of treating or preventing cancer in a mammal, methods of inhibiting the growth of a target cell, methods of producing the PE, and methods of producing the chimeric molecule are further provided by the invention.Type: GrantFiled: June 7, 2012Date of Patent: May 24, 2016Assignee: The United States of America, as represented by the Secretary, Department of Health and Human ServicesInventors: Ira H. Pastan, Ronit Mazor, Masanori Onda, Aaron Vassall, Richard Beers, Jaime Eberle, Wenhai Liu
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Patent number: 9279019Abstract: Disclosed herein are isolated human monoclonal antibodies that specifically bind human CD22 with a dissociation constant (Kd) of 25 nM or less. Nucleic acids encoding these antibodies, expression vectors including these nucleic acid molecules, and isolated host cells that express the nucleic acid molecules are also disclosed. The antibodies can be used to detect human CD22 in a sample. In some cases, CD22 is soluble CD22. Methods of diagnosing a B-cell malignancy, or confirming a B-cell malignancy diagnosis, are disclosed herein that utilize these antibodies. Methods of treating a subject with a B-cell malignancy are also disclosed.Type: GrantFiled: August 5, 2013Date of Patent: March 8, 2016Assignee: The United States of America as represented by the Secretary of the Department of Health and Human ServicesInventors: Dimiter S. Dimitrov, Xiaodong Xiao, Ira H. Pastan
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Publication number: 20160046677Abstract: The invention provides a Pseudomonas exotoxin A (PE) comprising an amino acid sequence having a substitution of one or more of amino acid residues E420, D463, Y481, L516, R563, D581, D589, and K606, wherein the amino acid residues are defined by reference to SEQ ID NO: 1. The invention further provides related chimeric molecules, as well as related nucleic acids, recombinant expression vectors, host cells, populations of cells, and pharmaceutical compositions. Methods of treating or preventing cancer in a mammal, methods of inhibiting the growth of a target cell, methods of producing the PE, and methods of producing the chimeric molecule are further provided by the invention.Type: ApplicationFiled: October 30, 2015Publication date: February 18, 2016Applicant: The United States of America, as represented by the Secretary, Department of Health and Human ServInventors: Ira H. Pastan, Masanori Onda, Wenhai Liu
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Patent number: 9249217Abstract: We have constructed bispecific antibody engaging molecules which have one arm that specifically engages a tumor cell which expresses the human EGFRvIII mutant protein on its surface, and a second arm that specifically engages T cell activation ligand CD3. The engaging molecules are highly cytotoxic and antigen-specific.Type: GrantFiled: November 15, 2011Date of Patent: February 2, 2016Assignees: Secretary, DHHS, Duke UniversityInventors: Darell D. Bigner, Chien-Tsun Kuan, John H. Sampson, Mingqing Cai, Bryan D. Choi, Ira H. Pastan
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Publication number: 20150368353Abstract: Recombinant scFv-immunotoxins target tumor cells expressing human podoplanin but not podoplanin-negative or normal cells. The immunotoxins can be used for treatment of malignant glioma patients or any malignant tumor expressing podoplanin. One such immunotoxin comprises a modified Pseudomonas exotoxin (PE38) attached to the scFv antibody fragment. This immunotoxin can be used as a therapeutic drug for the treatment of malignant gliomas and other cancers.Type: ApplicationFiled: June 1, 2015Publication date: December 24, 2015Inventors: Darell BIGNER, Chien-Tsun KUAN, Ira H. PASTAN, Vidyalakshmi CHANDRAMOHAN
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Patent number: 9206240Abstract: The invention provides a Pseudomonas exotoxin A (PE) comprising an amino acid sequence having a substitution of one or more of amino acid residues E420, D463, Y481, L516, R563, D581, D589, and K606, wherein the amino acid residues are defined by reference to SEQ ID NO: 1. The invention further provides related chimeric molecules, as well as related nucleic acids, recombinant expression vectors, host cells, populations of cells, and pharmaceutical compositions. Methods of treating or preventing cancer in a mammal, methods of inhibiting the growth of a target cell, methods of producing the PE, and methods of producing the chimeric molecule are further provided by the invention.Type: GrantFiled: September 13, 2012Date of Patent: December 8, 2015Assignee: The United States of America, as represented by the Secretary, Department of Helath and Human ServicesInventors: Ira H. Pastan, Masanori Onda, Wenhai Liu
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Patent number: 9175057Abstract: The PAGE4 gene is expressed in reproductive tissues, and is expressed in reproductive cancers, such as prostate cancer, uterine cancer, and testicular cancer. Immunogenic PAGE4 polypeptides are disclosed herein, as are nucleic acids encoding the immunogenic PAGE4 polypeptides, vectors including these polynucleotides, and host cells transformed with these vectors. These polypeptides, polynucleotides, vectors, and host cells can be used to induce an immune response to PAGE4. Diagnostic methods to detect PAGE4 are also described.Type: GrantFiled: February 10, 2011Date of Patent: November 3, 2015Assignee: The United States of America, as represented by the Secretary, Department of Health and Human ServicesInventors: Jeffrey Schlom, Kwong-Yok Tsang, Ira H. Pastan
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Publication number: 20150299317Abstract: The invention provides a chimeric antigen receptor (CAR) comprising an antigen binding domain comprising SEQ ID NOs: 1-6, a transmembrane domain, and an intracellular T cell signaling domain. Nucleic acids, recombinant expression vectors, host cells, populations of cells, antibodies, or antigen binding portions thereof, and pharmaceutical compositions relating to the CARs are disclosed. Methods of detecting the presence of cancer in a mammal and methods of treating or preventing cancer in a mammal are also disclosed.Type: ApplicationFiled: September 18, 2013Publication date: October 22, 2015Applicant: The United States of America,as represented by the Secretary, Department of Health and Human ServiceInventors: Rimas J. Orentas, Ira H. Pastan, Dimiter S. Dimitrov, Crystal L. Mackall