Patents by Inventor Ananthachari Srinivasan
Ananthachari Srinivasan 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: 5606028Abstract: Anchimeric chelates are disclosed which are capable of rapidly forming stable chelates with radionuclide metals at or below physiological temperature. Bifunctional anchimeric chelates having these same properties are also disclosed which are useful for radiolabeling target specific molecules such as monoclonal antibodies and fragments thereof.Type: GrantFiled: September 21, 1995Date of Patent: February 25, 1997Assignee: NeoRx CorporationInventors: Alan R. Fritzberg, Ananthachari Srinivasan
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Patent number: 5563250Abstract: The present invention provides cleavable conjugates whose linkers contain a labile bond that is cleavable under a variety of mild conditions, including weakly acidic. Since the agent may be bonded directly to the linker, cleavage can result in release of native agent. The invention also provides methods for producing cleavable conjugates. Preferred agents include drugs, toxins, biological response modifiers, radiodiagnostic compounds, radiotherapeutic compounds, and derivatives thereof. The targeting molecule employed in the invention may be an intact molecule, a fragment thereof, or a functional equivalent thereof. In a particularly preferred embodiment, the targeting molecule is a monoclonal antibody directed towards a tumor-associated antigen in man. The invention further provides methods for delivering to the cytoplasm of a target cell an agent free of its targeting molecule carrier.Type: GrantFiled: May 13, 1994Date of Patent: October 8, 1996Assignee: NeoRx CorporationInventors: Mark D. Hylarides, Ananthachari Srinivasan, Jeffrey N. Fitzner, Vivekananda M. Vrudhula
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Patent number: 5549883Abstract: A chemically defined polymeric carrier comprising a series of .alpha.-amino acids in any combination containing side chains to which diagnostic/therapeutic and chelating agents can be covalently joined through cleavable linkers either directly or covalently joined through cleavable linkers after chemical modification of the side chains. Hydrazone, disulfide, and ester linkages in any combination can be present in the polymeric carrier between the side chains of the .alpha.-amino acids and the agents. The presence of a particular covalent linkage between the side chain and the agent in the carrier is determined by the functional group present in the side chain of the .alpha.-amino acid and the functional group present in the agent. The .alpha.-amino acids with side chains to which agents do not covalently join can function as spacers to minimize interaction between bulky molecules attached to the polymeric carrier. In addition, those .alpha.Type: GrantFiled: June 3, 1993Date of Patent: August 27, 1996Assignee: NeoRx CorporationInventors: Ananthachari Srinivasan, Vivekananda M. Vrudhula, Diana I. Brixner
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Patent number: 5464934Abstract: Ligands that are capable of forming metal complexes are incorporated directly into peptides at nonbiologically active locations. The metal complex serves as a bifunctional agent and as a spacer molecule. In one aspect of the invention, the ligands are prepared by replacing a nonbiologically active peptide spacer sequence with either Cys-Gly-Gly-Glu(.gamma.-)CO- (SEQ ID NO:1) or Cys-Gly-Gly-Lys(.epsilon.-)NH-CO(CH.sub.2).sub.2 -CO- (SEQ ID NO:2). In these examples, unnatural peptide bonds are used to attach the ligand to the terminal end of the peptide. Peptides incorporating such ligands are also disclosed.Other spacer ligands which may be incorporated into peptides include the following natural peptide sequences: -Cys-Gly-His-, -Asp-Gly-Cys-, -Glu-Gly-Cys-, -Gly-Asp-Cys-, and -Gly-Glu-Cys-. Unnatural tripeptides which function as spacer ligands include: -Cys-Gly-(imidazolyl glycyl)-, -isoCys-Gly-(imidazolyl glycyl)-, and -isoCys-Gly-His-.Type: GrantFiled: May 14, 1993Date of Patent: November 7, 1995Assignee: Mallinckrodt Medical, Inc.Inventors: T. Jeffrey Dunn, Ananthachari Srinivasan, Leon R. Lyle, Raghavan Rajagopalan
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Patent number: 5436352Abstract: The present invention provides metal chelating compounds, to chelates and chelate-targeting agent conjugates formed from the chelating compounds, and to methods for making and using these compositions. The chelating compounds incorporate two nitrogen atoms and three sulfur atoms ("N.sub.2 S.sub.3 "), two nitrogen atoms and four sulfur atoms ("N.sub.2 S.sub.4 "), or three nitrogen atoms and three sulfur atoms ("N.sub.3 S.sub.3 "). Metals, and metal oxides, capable of being chelated by the compounds include those that are radionuclides, such as .sup.99m Tc and .sup.186/188 Re.The targeting agent portion of the chelate-targeting agent conjugates provided includes antibodies, peptides, hormones, enzymes and biological response modifiers. Methods for making the conjugates are provided and encompass the addition of a metal, or metal oxide, to a chelating compound prior to attachment to a targeting agent as well as subsequent to the attachment.Type: GrantFiled: December 6, 1991Date of Patent: July 25, 1995Assignee: NeoRx CorporationInventors: Ananthachari Srinivasan, Alan R. Fritzberg, David S. Jones
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Patent number: 5399710Abstract: Novel labeling reagents are useful for radiolabeling proteins such as antibodies with radionuclide metals such as .sup.99m Tc, .sup.186 Re, and .sup.188 Re. The reagents are of the following formula: ##STR1## wherein: each X is independently chosen from O, S, NH, or NR.sub.2, wherein R.sub.2 is a protecting group or an electron withdrawing group;R.sub.1 represents a protecting group, wherein each R.sub.1 is a separate protecting group or the two R.sub.1 symbols are taken together to represent a single protecting group; andeach T is independently chosen from hydrogen, lower alkyl groups of from 1 to about 6 carbon atoms, electron withdrawing groups, and lower alkyl groups of from 1 to about 6 carbon atoms substituted with electron withdrawing group(s).Type: GrantFiled: December 22, 1992Date of Patent: March 21, 1995Assignee: NeoRx CorporationInventors: Sudhakar Kasina, Ananthachari Srinivasan, James Sanderson, Alan R. Fritzberg
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Patent number: 5310536Abstract: Amide-thiolate ligands having improved metal chelate formation kinetics are disclosed. The ligands include a tertiary amine strategically located to facilitate rapid formation of an amine-amide-thiolate intermediate complex, followed by transfer of the metal to a thermodynamically stable amide-thiolate complex. The amide-thiolate ligands of the present invention may be used for post formed labeling of biological substances for use in the fields of diagnosis and therapy.Type: GrantFiled: February 6, 1992Date of Patent: May 10, 1994Assignee: Mallinckrodt Medical, Inc.Inventor: Ananthachari Srinivasan
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Patent number: 5283342Abstract: Methods, compounds, compositions and kits that relate to pretargeted delivery of diagnostic and therapeutic agents are disclosed. In particular, methods for radiometal labeling of biotin and for improved radiohalogenation of biotin, as well as related compounds, are described.Type: GrantFiled: June 9, 1992Date of Patent: February 1, 1994Assignee: NeoRx CorporationInventors: Linda M. Gustavson, Ananthachari Srinivasan, Alan R. Fritzberg, John M. Reno, Donald B. Axworthy
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Patent number: 5252721Abstract: Novel chelating compounds and the corresponding radionuclide metal chelates are useful for radiolabeling proteins such as antibodies with radionuclide metals such as .sup.99m Tc, .sup.186 Re, and .sup.188 Re. The chelating compounds are of the following formulas: ##STR1## wherein each R is a protecting group;Q is hydrogen or a protecting group;each T is independently chosen from hydrogen, lower alkyl groups of from 1 to about 6 carbon atoms, electron withdrawing groups, and lower alkyl groups of from 1 to about 6 carbon atoms substituted with electron withdrawing group(s);X represents O, S, or NH;each R' is independently selected from:--(CH.sub.2).sub.n --COOH with n=0 to about 4,--(CH.sub.2).sub.n --Z, wherein Z represents a conjugation group and n is 0 to about 4,hydrogen, anda lower alkyl group of from 1 to about 6 carbon atoms;each R" is independently selected from:--(CH.sub.2).sub.Type: GrantFiled: September 28, 1990Date of Patent: October 12, 1993Assignee: NeoRx CorporationInventors: Sudhakar Kasina, Ananthachari Srinivasan
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Patent number: 5250666Abstract: Chelating compounds of specified structure are useful for radiolabeling targeting proteins such as antibodies. The radiolabeled antibodies, or catabolites thereof, demonstrate improved biodistribution properties, including reduced localization within the intestines.Type: GrantFiled: November 6, 1992Date of Patent: October 5, 1993Assignee: NeoRx CorporationInventors: Linda M. Gustavson, Ananthachari Srinivasan, Sudhakar Kasina, Alan R. Fritzberg
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Patent number: 5242679Abstract: Protein conjugated chelated metal radionuclides are provided for use in vivo. Intermediates are provided for preparing the polypeptide compositions efficiently.Type: GrantFiled: August 31, 1990Date of Patent: September 7, 1993Assignee: NeoRx CorporationInventors: Alan R. Fritzberg, Sudhakar Kasina, Ananthachari Srinivasan, Daniel S. Wilbur
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Patent number: 5202451Abstract: Anchimeric chelates are disclosed which are capable of rapidly forming stable chelates with radionuclide metals at or below physiological temperature. Bifunctional anchimeric chelates having these same properties are also disclosed which are useful for radiolabeling target specific molecules such as monoclonal antibodies and fragments thereof.Type: GrantFiled: February 17, 1988Date of Patent: April 13, 1993Assignee: NeoRx CorporationInventors: Alan R. Fritzberg, Ananthachari Srinivasan
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Patent number: 5175257Abstract: Chelating compounds of specified N.sub.2 S.sub.2 N.sub.3 S derived structure are useful for radiolabeling targeting molecules such as antibodies. Cleavable ester orthioester linkers connect the radionuclide metal chelates to the antibodies. The radiolabeled antibodies have improved biodistribution properties, including reduced localization within the intestines and kidneys.Type: GrantFiled: January 14, 1991Date of Patent: December 29, 1992Assignee: NeoRx CorporationInventors: Sudhakar Kasina, Ananthachari Srinivasan, John M. Reno, Linda M. Gustavson, Jeffrey N. Fitzner, David S. Jones
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Patent number: 5175256Abstract: Novel labeling reagents are useful for radiolabeling proteins such as antibodies with radionuclide metals such as .sup.99m Tc, .sup.186 Re, and .sup.188 Re. The reagents are of the following formula: ##STR1## wherein: each X is independently chosen from O, S, NH, or NR.sub.2, wherein R.sub.2 is a protecting group or an electron withdrawing group;R.sub.1 represents a protecting group, wherein each R.sub.1 is a separate protecting group or the two R.sub.1 symbols are taken together to represent a single protecting group; andeach T is independently chosen from hydrogen, lower alkyl groups of from 1 to about 6 carbon atoms, electron withdrawing groups, and lower alkyl groups of from 1 to about 6 carbon atoms substituted with electron withdrawing group(s).Type: GrantFiled: September 28, 1990Date of Patent: December 29, 1992Assignee: NeoRx CorporationInventors: Sudhakar Kasina, Ananthachari Srinivasan, James Sanderson, Alan R. Fritzberg
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Patent number: 5175343Abstract: Protein conjugated chelated metal radionuclides are provided for use in vivo. Intermediates are provided for preparing the polypeptide compositions efficiently.Type: GrantFiled: June 19, 1987Date of Patent: December 29, 1992Assignee: NeoRx CorporationInventors: Alan R. Fritzberg, Sudhakar Kasina, Ananthachari Srinivasan, Daniel S. Wilbur
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Patent number: 5171563Abstract: A process for reducing the non-target organ accumulation of immunoconjugates administered in vivo during therapeutic or diagnostic procedures involves the use of immunoconjugates comprising linkers that are cleavable at the non-target organs. The linkers are cleavable under conditions present, or induced, at one or more non-target organs, which include the kidneys or the liver.Type: GrantFiled: February 10, 1992Date of Patent: December 15, 1992Assignee: NeoRx CorporationInventors: Paul G. Abrams, John M. Reno, Alan R. Fritzberg, Ananthachari Srinivasan, David C. Anderson
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Patent number: 5164176Abstract: Chelating compounds of specific structure are useful for radiolabeling targeting proteins such as antibodies. The radiolabeled antibodies, or catabolites thereof, demonstrate improved biodistribution properties, including reduced localization within the intestines.Type: GrantFiled: September 5, 1990Date of Patent: November 17, 1992Assignee: NeoRx CorporationInventors: Linda M. Gustavson, Ananthachari Srinivasan, Sudhakar Kasina, Alan R. Fritzberg
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Patent number: 5141648Abstract: The present invention provides cleavable conjugates whose linkers contain a labile bond that is cleavable under a variety of mild conditions, including weakly acidic. Since the agent may be bonded directly to the linker, cleavage can result in release of native agent. The invention also provides methods for producing cleavable conjugates. Preferred agents include drugs, toxins, biological response modifiers, radiodiagnostic compounds, radiotherapeutic compounds, and derivatives thereof. The targeting molecule employed in the invention may be an intact molecule, a fragment thereof, or a functional equivalent thereof. In a particularly preferred embodiment, the targeting molecule is a monoclonal antibody directed towards a tumor-associated antigen in man. The invention further provides methods for delivering to the cytoplasm of a target cell an agent free of its targeting molecule carrier.Type: GrantFiled: March 29, 1991Date of Patent: August 25, 1992Assignee: NeoRx CorporationInventors: Mark D. Hylarides, Ananthachari Srinivasan, Jeffrey N. Fitzner, Vivekananda M. Vrudhula
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Patent number: 5120526Abstract: Protein conjugated chelated metal radionuclides are provided for use in vivo. Intermediates are provided for preparing the polypeptide compositions efficiently.Type: GrantFiled: February 4, 1991Date of Patent: June 9, 1992Assignee: NeoRx CorporationInventors: Alan R. Fritzberg, Sudhakar Kasina, Ananthachari Srinivasan, Daniel S. Wilbur
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Patent number: 5112954Abstract: The activity of cytotoxic agents on target cells is enhanced through administration of a sensitizing agent to a patient prior to or simultaneously with administration of the cytotoxic agent. One or both of the two types of agents are attached to antibodies specific for the desired target cells, thereby enhancing the cytotoxic effect on target cells compared to non-target cells. The sensitizer and/or the cytotoxic agent may be attached to monoclonal antibodies specific for cancer cells to selectively eradicate the cancer cells while minimizing toxicity toward normal tissues.Type: GrantFiled: April 4, 1988Date of Patent: May 12, 1992Assignee: NeoRx CorporationInventors: Paul G. Abrams, Ananthachari Srinivasan, Vivekananda M. Vrudhula