1
338 PATENT ABSTRACTS 4~M39 PRODUCTION AND USE OF MONOCLONAL ANTIBODIES TO PHOSPHOTYROSINE- CONTAINING PROTEINS A Raymond Frackelton, Herman N Eisen, Alonzo H Ross assigned to Massachusetts In- stitute of Technology A hybridoma cell line is disclosed that secretes monoelonal antibodies which serve as a high titer, reproducible, biological reagent useful in biological/medical research for isolating and identifying phosphotyrosine-containing pro- teins. In addition, the antibodies have potential uses in diagnosis of a variety of diseases, in- cluding certain cancers. The antibodies, which have demonstrated affinity for a variety of molecules containing o-phosphotyrosine residues, were prepared using a synthetic analog, p-azobenzyl phosphonate (ABP) covalently linked to a carrier protein, as the antigen. 4544545 LIPOSOMES CONTAINING MODIFIED CHOLESTEROL FOR ORGAN TARGETING Patrick J Ryan, Michael A Davis, Donald L Melchior assigned to Trustees University of Massachusetts Phospholipid liposomes are provided having an outer layer including a cholesterol derivative such as a cholesterol ester and an aqueous medium confined by the layer which includes a tracer agent, a cytoxic agent or a therapeutic a- gent. The liposomes are adapted for specific or- gan targeting. 4544634 METHOD OF PRODUCING ACYCLOVIR Thomas A Krenitsky assigned to Burroughs Wellcome Co The novel compound 6-deoxyacyciovir is en- zymatically converted to acyclovir by xanthine oxidase/dehydrogenase or aldehyde oxidase in vivo, i.e. within the body of the animal being treated. The enzymatic conversion may also be effected ex vivo (i.e. in vitro) as a method of syn- thesizing acyclovir. 4545985 PSEUDOMONAS EXOTOXIN CONJUGATE IMMUNOTOXINS Ira Pastan, Mark C Willingham, David J Fitz- gerald assigned to The United States of America as represented by the Secretary Dept of Health and Human Services A method of modifying Pseudomonas exotoxin (PE) with methyl-4-mercaptobutyrimidate is dis- closed so that after conjugating the exotoxin to a monoclonal antibody (ab) such as the antibody to the transferrin receptor, the PE-ab conjugate becomes a highly potent immunotoxin suitable for use against human tumor cells. This same method has been used to conjugate PE to epi- dermal growth factor (EGF) to create a highly potent growth factor-toxin conjugate for use against cells having large numbers of EGF recep- tors. Also disclosed are the immunotoxin con- jugates for Pseudomonas exotoxin coupled to anti-TFR (antibody to the transferrin receptor) and anti-TAC (antibody to the human T-cell growth factor receptor) and to EGF. 4~59~ TIMOTHY GRASS ANTIGEN SPECIFIC ANTI-IDIOTYPIC ANTIBODIES Arthur Malley assigned to Research Corpora- tion This invention provides a number of immuno- logical reagents useful for the suppression of al- lergic reactions induced by Timothy-grass pollen allergen (or cross-reacting allergens thereof) and for methods of obtaining said reagents. The rea- gents include: (l) an anti-idiotypic antibody (anti-IgEid) directed to the allergen (Timothy grass antigen) binding site of an IgE immuno- globulin; (2) an anti-idiotypic antibody directed to the allergenic T-cell helper factor (THF) derived from Timothy grass pollen antigen stimulated lymphocytes; (3) unique methods for generating antigen-specific T-suppressor cells (TS); (4) a unique method for producing antigen- specific suppressor T cell factors (TSF); (5) a method for fractionation of TSF; and (6) a specific T cell factor, TSF2. The invention fur- ther provides pharmaceutical compositions

4545985 Pseudomonas exotoxin conjugate immunotoxins

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338 PATENT ABSTRACTS

4 ~ M 3 9

P R O D U C T I O N A N D U S E O F M O N O C L O N A L A N T I B O D I E S T O

P H O S P H O T Y R O S I N E - C O N T A I N I N G P R O T E I N S

A Raymond Frackelton, Herman N Eisen, Alonzo H Ross assigned to Massachusetts In- stitute of Technology

A hybridoma cell line is disclosed that secretes monoelonal antibodies which serve as a high titer, reproducible, biological reagent useful in biological/medical research for isolating and identifying phosphotyrosine-containing pro- teins. In addition, the antibodies have potential uses in diagnosis of a variety of diseases, in- cluding certain cancers. The antibodies, which have demonstrated affinity for a variety of molecules containing o-phosphotyrosine residues, were prepared using a synthetic analog, p-azobenzyl phosphonate (ABP) covalently linked to a carrier protein, as the antigen.

4544545

L I P O S O M E S C O N T A I N I N G M O D I F I E D C H O L E S T E R O L F O R

O R G A N T A R G E T I N G

Patrick J Ryan, Michael A Davis, Donald L Melchior assigned to Trustees University of Massachusetts

Phospholipid liposomes are provided having an outer layer including a cholesterol derivative such as a cholesterol ester and an aqueous medium confined by the layer which includes a tracer agent, a cytoxic agent or a therapeutic a- gent. The liposomes are adapted for specific or- gan targeting.

4544634

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

Thomas A Krenitsky assigned to Burroughs Wellcome Co

The novel compound 6-deoxyacyciovir is en- zymatically converted to acyclovir by xanthine oxidase/dehydrogenase or aldehyde oxidase in vivo, i.e. within the body of the animal being treated. The enzymatic conversion may also be

effected ex vivo (i.e. in vitro) as a method of syn- thesizing acyclovir.

4545985

P S E U D O M O N A S E X O T O X I N C O N J U G A T E I M M U N O T O X I N S

Ira Pastan, Mark C Willingham, David J Fitz- gerald assigned to The United States of America as represented by the Secretary Dept of Health and Human Services

A method of modifying Pseudomonas exotoxin (PE) with methyl-4-mercaptobutyrimidate is dis- closed so that after conjugating the exotoxin to a monoclonal antibody (ab) such as the antibody to the transferrin receptor, the PE-ab conjugate becomes a highly potent immunotoxin suitable for use against human tumor cells. This same method has been used to conjugate PE to epi- dermal growth factor (EGF) to create a highly potent growth factor-toxin conjugate for use against cells having large numbers of EGF recep- tors. Also disclosed are the immunotoxin con- jugates for Pseudomonas exotoxin coupled to anti-TFR (antibody to the transferrin receptor) and anti-TAC (antibody to the human T-cell growth factor receptor) and to EGF.

4 ~ 5 9 ~

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

A N T I B O D I E S

Arthur Malley assigned to Research Corpora- tion

This invention provides a number of immuno- logical reagents useful for the suppression of al- lergic reactions induced by Timothy-grass pollen allergen (or cross-reacting allergens thereof) and for methods of obtaining said reagents. The rea- gents include: (l) an anti-idiotypic antibody (anti-IgEid) directed to the allergen (Timothy grass antigen) binding site of an IgE immuno- globulin; (2) an anti-idiotypic antibody directed to the allergenic T-cell helper factor (THF) derived from Timothy grass pollen antigen stimulated lymphocytes; (3) unique methods for generating antigen-specific T-suppressor cells (TS); (4) a unique method for producing antigen- specific suppressor T cell factors (TSF); (5) a method for fractionation of TSF; and (6) a specific T cell factor, TSF2. The invention fur- ther provides pharmaceutical compositions