4865980 monoclonal antibodies for dna-ran hybrid complexes and their uses

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PATENT ABSTRACTS 463 Antibodies raised against a synthetic replicate of 4865841 the N-terminal six residues of the 18 kD chain are effective to reduce the activity of highly METHODS AND COMPOSITIONS purified 32 kD inhibin and may be administered FOR TRANSIENT ELIMINATION to mammalian animals for the purpose of OF HUMORAL IMMUNE neutralizing endogenous inhibin and thereby in- ANTIBODIES creasing gonadotropin secretion. The antibodies are also useful in immunoassays to determine in- hibin levels in mammalian fluids. To generate Joseph P Baiint, Sharo Cochran, Frank Jones, the antibodies, short chain peptides are syn- Harry Snyder assigned to lmre Corporation thesized which mimic portions of natural mam- malian inhibin protein chains, the synthetic Antibody is removed from the blood of patients peptides are conjugated to large carrier who are being treated or diagnosed with ex- molecules and the conjugates are used as in- ogenous macromolecules, such as immuno- oculum to induce a mammalian immune system toxins. As the immunotoxins are foreign to produce inhibin-reactive antibodies, antigens, the patient will" develop an immune response. The antibodies produced by the im- mune response upon subsequent immunization 4864020 with the immunotoxins will interfere with the desired function of the immunotoxins by pre- MONOCLONAL ANTIBODIES venting them from binding with their specific AND CELL LINES FOR target site. By extracorporeally removing the PARATHYROID TISSUE-SPECIFIC antibodies, the activity of the immunotoxins can ANTIGEN PARATHYROID- be enhanced. SPECIFIC 4865971 William G Cance, Joseph M Davie, Samuel A Wells, William G Dilley, Michael J Welch, MONOCLONAL ANTIBODY Jeremiah J Morrissey assigned to Washington SPECIFIC TO A COMMON University School of Medicine DETERMINANT SITE OF Monoclonal antibodies specific for an antigen NEUTROPHILS AND present on the surface of parathyroid tissue are EOSINOPHILS useful in imaging such tissue when conjugated to suitable label. The antibodies of the invention Kenneth Kortright, David E Hofheinz, Gary bind exclusively to parathyroid surfaces and do Toedter assigned to Coulter Corporation not bind to other tissues. The antibodies are use- ful in establishing the location of the parathyroid A hybrid cell line capable of producing mono- whether in its normal location or in ectopic clonal antibodies uniquely specific to human placements. An exemplary monoclonal has been neutrophils and eosinophils and exhibiting no deposited at the American Type Culture Collec- specificity for lymphocytes, basophils and tion and has accession number ATCC No. monocytes. Further thereisnoreactivitywithac- HB9917. ute leukemia cells. One of the partners in the hybridoma fusion of a mouse spleen cell 4865835 developed from using human granulocytes as the immunization agent. The monoclonal antibody further is capable of being used to enumerate and DIAGNOSIS AND TREATMENT isolate neutrophils in normal peripheral blood OF TUMORS and possibly in blood of patients with acute leukemia. Richard H J Begent, London S W 19, United Kingdom 4865980 There are disclosed liposomes to which are MONOCLONAL ANTIBODIES linked agents which are capable of binding an anti-tumor antibody. The liposomes are useful in FOR DNA-RNA HYBRID the detection and treatment of tumors by reason COMPLEXES AND THEIR USES of their ability to remove non-specifically dist- ributed anti-tumor antibodies from vascular and W Dorse Stuart, Mark B Frank assigned to other extra-cellular spaces. University of Hawaii

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PATENT ABSTRACTS 463

Antibodies raised against a synthetic replicate of 4865841 the N-terminal six residues of the 18 kD chain are effective to reduce the activity of highly M E T H O D S A N D C O M P O S I T I O N S purified 32 kD inhibin and may be administered FOR TRANSIENT ELIMINATION to mammalian animals for the purpose of O F H U M O R A L I M M U N E neutralizing endogenous inhibin and thereby in- A N T I B O D I E S creasing gonadotropin secretion. The antibodies are also useful in immunoassays to determine in- hibin levels in mammalian fluids. To generate Joseph P Baiint, Sharo Cochran, Frank Jones, the antibodies, short chain peptides are syn- Harry Snyder assigned to lmre Corporation thesized which mimic portions of natural mam- malian inhibin protein chains, the synthetic Antibody is removed from the blood of patients peptides are conjugated to large carrier who are being treated or diagnosed with ex- molecules and the conjugates are used as in- ogenous macromolecules, such as immuno- oculum to induce a mammalian immune system toxins. As the immunotoxins are foreign to produce inhibin-reactive antibodies, antigens, the patient will" develop an immune

response. The antibodies produced by the im- mune response upon subsequent immunization

4864020 with the immunotoxins will interfere with the desired function of the immunotoxins by pre-

M O N O C L O N A L A N T I B O D I E S venting them from binding with their specific A N D C E L L L I N E S F O R target site. By extracorporeally removing the

P A R A T H Y R O I D T I S S U E - S P E C I F I C antibodies, the activity of the immunotoxins can A N T I G E N P A R A T H Y R O I D - be enhanced.

S P E C I F I C

4865971 William G Cance, Joseph M Davie, Samuel A Wells, William G Dilley, Michael J Welch, M O N O C L O N A L A N T I B O D Y Jeremiah J Morrissey assigned to Washington S P E C I F I C T O A C O M M O N University School of Medicine D E T E R M I N A N T S I T E O F

Monoclonal antibodies specific for an antigen N E U T R O P H I L S A N D present on the surface of parathyroid tissue are E O S I N O P H I L S useful in imaging such tissue when conjugated to suitable label. The antibodies of the invention Kenneth Kortright, David E Hofheinz, Gary bind exclusively to parathyroid surfaces and do Toedter assigned to Coulter Corporation not bind to other tissues. The antibodies are use- ful in establishing the location of the parathyroid A hybrid cell line capable of producing mono- whether in its normal location or in ectopic clonal antibodies uniquely specific to human placements. An exemplary monoclonal has been neutrophils and eosinophils and exhibiting no deposited at the American Type Culture Collec- specificity for lymphocytes, basophils and tion and has accession number ATCC No. monocytes. Further thereisnoreactivitywithac- HB9917. ute leukemia cells. One of the partners in the

hybridoma fusion of a mouse spleen cell 4865835 developed from using human granulocytes as the

immunization agent. The monoclonal antibody further is capable of being used to enumerate and

D I A G N O S I S A N D T R E A T M E N T isolate neutrophils in normal peripheral blood OF TUMORS and possibly in blood of patients with acute

leukemia. Richard H J Begent, London S W 19, United Kingdom 4865980

There are disclosed liposomes to which are M O N O C L O N A L A N T I B O D I E S linked agents which are capable of binding an anti-tumor antibody. The liposomes are useful in F O R D N A - R N A H Y B R I D the detection and treatment of tumors by reason C O M P L E X E S A N D T H E I R U S E S of their ability to remove non-specifically dist- ributed anti-tumor antibodies from vascular and W Dorse Stuart, Mark B Frank assigned to other extra-cellular spaces. University of Hawaii

464 PATENT ABSTRACTS

Monoclonal antibodies are provided capable of caused by defective genes. After delivery of the distinguishing DNA-RNA hybrid complexes genetic material, t h e replication-defective from single stranded DNA and RNA and double character of the viral vector prevents its stranded DNA and RNA. The antibodies find reproduction. particular use in determining the presence of a specific nucleic acid sequence on a solid surface. Single stranded polynucleotide is fixed to a solid 4866071 (gel) surface and then hybridized with the com- plementary probe. The hybrid complex specific M E T H O D O F I N H I B I T I N G monoclonal antibody is then added to bind to L E U K E M I A S A N D S A R C O M A S IN any hybrid crmplexes which have formed. By A M A M M A L I A N H O S T appropriate label, the hybrid complex may be

visualized in a variety of ways. George R Pettit assigned to Arizona Board of Regents

4865998 A new antineoplastic substance denominated pancratistatin. Methods of isolating natural and

M O N O C L O N A L A N T I B O D I E S T O synthetic pancratistatin and 7-deoxynarciclasine H U M A N L U N G C A N C E R S A N D and the pharmaceutically acceptable derivatives

M E T H O D thereof to make a pharmaceutical preparation therefrom and methods for treating a host af-

Hans-Joachim Feickert, Wolfgang Rettig, flicted with a neoplasm with said preparations. Karen Chorney, Carlos Cordon-Cardo, Myron R Melamed, Kenneth O Lloyd, Herbert F Oett- gen, Lloyd J 'Old, Bernd Anger assigned to 4867962 Sloan-Kettering Institute for Cancer Research

F U N C T I O N A L L Y S P E C I F I C A panel of monoclonal antibodies produced A N T I B O D I E S from normal human lung fibroblasts and human lung tumors as immunogen is used to diagnose the presence of lung tumors and differentiate Paul G Abrams assigned to NeoRx Corporation between those which are benign and those which are cancerous. Diagnostic or therapeutic agents are attached to

two or more antibody species having non- overlapping patterns of cross-reactivity to in-

4866042 crease the relative amount of the active agent(s) delivered to desired target cells compared to

M E T H O D F O R T H E D E L I V E R Y non-target cells. The agents may be attached to O F G E N E T I C M A T E R I A L A C R O S S monoclonal antibodies which bind to cancer

cells so that a higher percentage of the active T H E B L O O D B R A I N B A R R I E R agent(s) localize on the target cells compared to

each type of cross-reactive normal tissue. Edward Neuwelt

A method for treating genetic and acquired 4867973 brain disorders is disclosed in which genetic material is introduced into the blood stream for delivery to the brain. Prior to delivery, the inter- A N T I B O D Y - T H E R A P E U T I C endothelial structure of the BBB is chemically A G E N T C O N J U G A T E S altered to permit passage of the genetic material therethrough. This is accomplished through os- John W F Goers, Hurley D King, Chyi Lee, motic disruption of the BBB by administration Daniel Coughlin, Vernon Alvarez, John D Rod- of suitable chemical agents. Prior to administra- well, Thomas McKearn assigned to Cytogen tion, the genetic material can be inserted within Corporation the genome of a viral vector preferably incapable of replication in vivo. After crossing the blood This invention relates to antibody-therapeutic a- brian barrier, the vector containing the genetic gent conjugates having a therapeutic agent cova- material enters the brain tissues where it delivers lently attached to an antibody or antibody in a site-specific manner the genetic material in fragment. Also described are methods for inter- order to control adverse effects of the disease mediates in the preparation of antibody con-