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PATENT ABSTRACTS 459 wherein the polypeptide includes: (a) a four 4861581 amino acid sequence which corresponds to the four amino acid sequence of a beta-turn of the DETECTION OF NECROTIC protein; (b) a sequence of two to eight amino acid MALIGNANT TISSUE AND residues attached to the amino terminal (H2N-) ASSOCIATED THERAPY of the four amino acid sequence; and (c) a sequence of two to eight amino acid residues at- Alan Epstein, Clive Taylor assigned to Cancer tached to the carboxyl terminal (-COOH) of the Biologics Inc four amino acid sequence, wherein the amino acid residues of subparts (b) and (c) correspond to those attached to the amino terminal and the Disclosed is a method for measuring the effec- carboxyl terminal, respectively of the beta-turn tiveness of therapy intended to kill malignant of the protein, and the pharmaceutically ac- cells in vivo in a mammal, comprising the steps ceptable salts of the polypeptide. The invention of obtaining monoclonal antibody that is specific to an internal cellular component of the relates to a conjugate which comprises the poly- peptide described above with a macromolecular mammal but not to external cellular compo- carrier. The invention also relates to antibodies nents, wherein the monoclonal antibody is and the production thereof which are specific for labeled; contacting the labeled antibody with tis- the polypeptide or the conjugate of the peptide sue of a mammal that has received therapy to kill described above. The synthetic polypeptide malignant cells in vivo,oand determining the el- sequences, peptide conjugates and antibodies fectiveness of the therapy by measuring the bi- thereof are useful as antigens in the production nding of the labeled antibody to the internal cellular component. The internal cellular com- of vaccines, antiviral agents, diagnostic reagents and the like, for the detection and treatment of ponent is preferably insoluble intracellular anti- infectious and immune diseases such as polio gen, and the label is preferably a radionuclide, a and cancer, and the like in mammals, par- radiopaque material, or a magnetic resonance- ticularly human beings, enhancing material. Also disclosed is a method whereby the antibody to insoluble intracellular antigen is conjugated to an antineoplastic agent, so that upon administration of the antibody- antineoplastic agent conjugate, antineoplastic a- gent may be delivered to the tumor. Also disclosed are antibodies for use with the fore- going methods. 4859769 4861709 ANTIVIRAL AGENTS DETECTION AND/OR IDENTIFICATION OF Karl-Anders Karlsson, Erling Norrby, Goran MICROORGANISMS IN A TEST Wadell, Gothenburg, Sweden assigned to SAMPLE USING Symbicom AB BIOLUMINESCENCE OR OTHER EXOGENOUS GENETICALLY- A second-step virus binding receptor is found in INTRODUCED MARKER nature on the surface of animal and plant cells. This receptor is thought to be needed for virus Shimon Y Ulitzur, Jonathan C Kuhn, Haifa, Is- penetration into target cells. The second-step rael assigned to Technicon Research A G receptor has been found to bind a wide variety of viruses belonging to a number of different A method for determining the presence of families. The second-step receptor and natural microorganisms in a tests sample. Exogenous or synthetic substances which correspond to or DNA containing a luminescent system or other are analogous to the binding epitope of the genetic marker system derived from a suitable second-step receptor in that they are able to bind donor source is introduced by genetic means into to a site on the virus which recognizes the bi- a host microorganism which lacks or poorly ex- nding epitope of the natural second-step recep- presses the donor DNA and whose presence it is tor, are therefore indicated for the diagnosis, desired to detect. Expression of the donor gene prophylaxis or treatment of viral infections, system allows the detection of the host micro-

4861709 Detection and/or identification of microorganisms in a test sample using bioluminescence or other exogenous genetically-introduced marker

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PATENT ABSTRACTS 459

wherein the polypeptide includes: (a) a four 4861581 amino acid sequence which corresponds to the four amino acid sequence of a beta-turn of the D E T E C T I O N O F N E C R O T I C protein; (b) a sequence of two to eight amino acid M A L I G N A N T T I S S U E A N D residues attached to the amino terminal (H2N-) A S S O C I A T E D T H E R A P Y of the four amino acid sequence; and (c) a sequence of two to eight amino acid residues at-

Alan Epstein, Clive Taylor assigned to Cancer tached to the carboxyl terminal (-COOH) of the Biologics Inc four amino acid sequence, wherein the amino acid residues of subparts (b) and (c) correspond to those attached to the amino terminal and the Disclosed is a method for measuring the effec- carboxyl terminal, respectively of the beta-turn tiveness of therapy intended to kill malignant of the protein, and the pharmaceutically ac- cells in vivo in a mammal, comprising the steps ceptable salts of the polypeptide. The invention of obtaining monoclonal antibody that is

specific to an internal cellular component of the relates to a conjugate which comprises the poly- peptide described above with a macromolecular mammal but not to external cellular compo- carrier. The invention also relates to antibodies nents, wherein the monoclonal antibody is and the production thereof which are specific for labeled; contacting the labeled antibody with tis- the polypeptide or the conjugate of the peptide sue of a mammal that has received therapy to kill described above. The synthetic polypeptide malignant cells in vivo,oand determining the el- sequences, peptide conjugates and antibodies fectiveness of the therapy by measuring the bi- thereof are useful as antigens in the production nding of the labeled antibody to the internal

cellular component. The internal cellular com- of vaccines, antiviral agents, diagnostic reagents and the like, for the detection and treatment of ponent is preferably insoluble intracellular anti- infectious and immune diseases such as polio gen, and the label is preferably a radionuclide, a and cancer, and the like in mammals, par- radiopaque material, or a magnetic resonance- ticularly human beings, enhancing material. Also disclosed is a method

whereby the antibody to insoluble intracellular antigen is conjugated to an antineoplastic agent, so that upon administration of the antibody- antineoplastic agent conjugate, antineoplastic a- gent may be delivered to the tumor. Also disclosed are antibodies for use with the fore- going methods.

4859769 4861709

A N T I V I R A L A G E N T S D E T E C T I O N A N D / O R

I D E N T I F I C A T I O N O F Karl-Anders Karlsson, Erling Norrby, Goran M I C R O O R G A N I S M S I N A T E S T Wadell, Gothenburg, Sweden assigned to S A M P L E U S I N G Symbicom AB B I O L U M I N E S C E N C E O R O T H E R

E X O G E N O U S G E N E T I C A L L Y - A second-step virus binding receptor is found in I N T R O D U C E D M A R K E R nature on the surface of animal and plant cells. This receptor is thought to be needed for virus Shimon Y Ulitzur, Jonathan C Kuhn, Haifa, Is- penetration into target cells. The second-step rael assigned to Technicon Research A G receptor has been found to bind a wide variety of viruses belonging to a number of different A method for determining the presence of families. The second-step receptor and natural microorganisms in a tests sample. Exogenous or synthetic substances which correspond to or DNA containing a luminescent system or other are analogous to the binding epitope of the genetic marker system derived from a suitable second-step receptor in that they are able to bind donor source is introduced by genetic means into to a site on the virus which recognizes the bi- a host microorganism which lacks or poorly ex- nding epitope of the natural second-step recep- presses the donor DNA and whose presence it is tor, are therefore indicated for the diagnosis, desired to detect. Expression of the donor gene prophylaxis or treatment of viral infections, system allows the detection of the host micro-

460 PATENT ABSTRACTS

organism. Compositions of bacteriophages and growth factor and purified insulin-like growth plasmids as well as a method for detection of factor. antibiotics in a test sample are described.

4861720 4861759

O N C O R N A V I R U S V A C C I N E S A N D F E L I N E A L P H A - T Y P E A N T I V I R A L C O M P O S I T I O N S

I N T E R F E R O N A N D M E T H O D S

Neils C Pedersen, Janet Yamamoto assigned to Hiroaki Mitsuya, Samuel Broder assigned to Regents of the University of California The United States of America as represented by

the Department of Health and Human Services Retroviral vaccines are provided comprising in- competent retroviruses containing defective Compositions containing 2',3'- RNA produced by growing viral transformed dideoxyadenosine, 2',Y-dideoxyinosine, and cells in the presence of interferon. The resulting dideoxyguanosine and their triphosphates for defective viruses by themselves or in combina- use in treating retroviral infections including ac- tion with interferon can be used as vaccines for quired immune deficiency syndrome (AIDS) are immunizing viral sensitive hosts against infec- disclosed with preferred methods of treatment tion. A novel feline interferon is produced in cul- which provide protection against cytopathic ef- ture with cells infected with the defective non- fects of human immunodeficiency virus (HIV). infectious retroviruses.

4861754 4863713

B A C T E R I O C I N S A N D C O M P O S I T I O N S T H E R E O F I N M E T H O D A N D S Y S T E M F O R

A N T I - V I R A L T R E A T M E N T A D M I N I S T E R I N G T H E R A P E U T I C A N D D I A G N O S T I C A G E N T S

Hannah Farkas-Himsley, Toronto, Ontario, M4W 2B1, Canada David A Goodwin, Claude Meares, Michae

McCall assigned to The Board of Trustees of It has been found that bacteriocins are able to Leland Stanford Jr Univ kill virally-infected mammalian cells, including virally infected white blood cells. Accordingly, A method and system for localizing a diagnostic viral infections can be detected and ultimately or therapeutic agent to an internal target site. treated using the bacteriocins and the methods The system includes (1) an epitopic compound, described herein. The invention is particularly (2) a binding protein which is effective to bind suited to detection and treatment of AIDS infec- specifically with the compound and capable of tion and infectious mononucleosis infection, localizing selectively at the target tissue, when

administered parenterally, and (3) a cleating a- gent which can bind to and cross-link the binding

4861757 protein, to form a protein aggregate which is readily cleared from the subject's bloodstream.

W O U N D H E A L I N G A N D B O N E In practicing the method of the invention, the bi- nding protein is administered to the subject

R E G E N E R A T I O N U S I N G P D G F parenterally, and allowed to localize at the target A N D I G F - I site, typically within 1-4 days. This is followed by

a chase with the cleating agent to remove cir- Harry N Antoniades, Samuel Lynch, Ray Wil- culating, but not target-localized binding pro- liams assigned to Institute of Molecular Biology; tein. When the epitopic compound is President and Fellows of Harvard Colle administered, binding of the compound to the

localized binding protein, and rapid clearance of Healing an external wound or regenerating bone unbound compound by the kidneys, results in of a mammal by administering to the mammal a selective localization of the compound at the tar- composition containing purified platelet-derived get site.