Exponential Biotherapies, Inc.

The United States of America As Represented by the Department of Health

National Institutes of Health, a Component of the US Dept. of Health & Human Services

The United States of America As Represented by the Secretary of

University of Delhi Department of Biochemistry

Sankar L Adhya

Carl R Merril

Richard M Carlton

Ira H Pastan

David J FitzGerald

Vijay Kumar Chaudhary

Amita Gupta

Dean Scholl

The present invention relates to a process of obtaining recombinant lambdoid bacteriophage with high density display of functional peptides and proteins on surface of said phage comprising of: constructing a donor plasmid having a nucleotide sequence that defines the elements for replication of the vector in bacteria, a selectable marker, a nucleotide sequence flanked by two non-compatible recombination sequences, and an inducible cistron for expression of a capsid protein and a fusion protein; constructing a recipient phage having a nucleotide sequence that defines the lambdoid elements for replication and packaging of the vector into an assembled bacteriophage and encodes an inducible cistron for expression of a selectable marker flanked by two non-compatible recombination sequences; transferring the said donor plasmid to said recipient plasmid to obtain cointegrates; growing said cointegrates in selective liquid medium; harvesting phages displaying protein encoded by the foreign DNA encapsulated in said harvested phage particle.

Lambda phage display system and the process

The present invention is directed to bacteriophage therapy, using methods which enable the bacteriophage to delay inactivation by any and all parts of the host defense system (HDS) against foreign objects. The HDS normally reduces the number of bacteriophage in an animal, which decreases the efficiency of the bacteriophage in killing the host bacteria present during an infection. Disclosed is a method of producing bacteriophage modified for anti-HDS purposes by physico-chemical alteration of the bacteriophage surface proteins, so that the altered bacteriophage remain active in the body for longer periods of time than the unmodified bacteriophage.

Antibacterial therapy with bacteriophage physico-chemically altered by pegylation to delay inactivation by the host defense system

The present invention discloses compositions and methods for the prophylaxis and treatment of bacterial infections by the use of polyvalent bacteriophage having multiple host range.

Bacteriophage having multiple host range

The present invention is directed to bacteriophage therapy, using methods that enable the bacteriophage to delay inactivation by any and all parts of the host defense system (HDS) against foreign objects that would tend to reduce the numbers of bacteriophage and/or the efficiency of those phage at killing the host bacteria in an infection. Disclosed is a method of producing bacteriophage modified for anti-HDS purposes, one method being selection by serial passaging of a bacteriophage, and the other method being genetic engineering of a bacteriophage, so that the modified bacteriophage will remain active in the body for longer periods of time than the wild-type phage.

Bacteriophage genotypically modified to delay inactivations by the host

The present invention is directed to bacteriophage therapy, using methods that enable the bacteriophage to delay inactivation by any and all parts of the host defense system (HDS) against foreign objects that would tend to reduce the numbers of bacteriophage and/or the efficiency of those phage at killing the host bacteria in an infection. Disclosed is a method of producing bacteriophage modified for anti-HDS purposes, one method being selection by serial passaging, and the other method being genetic engineering of a bacteriophage, so that the modified bacteriophage will remain active in the body for longer periods of time than the wild-type phage.

Antibacterial therapy with bacteriophage genotypically modified to delay

Modified Pseudomonas exotaxins which comprise deletions in at least domain 1A are taught. The toxins exhibit reduced cytotoxicity.

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Gaithersburg, MD, United States of America

Sankar L Adhya