American Cyanamid Company

Yeda Research and Develpment & Co. Ltd

American Cyanamid

Peter Bohlen

Andrew P Seddon

Joseph M Backer

Yakov Gluzman

Peter Gautschi-Sova

Phaik-Eng Sum

Susan Mancini Cady

Brian Lee Buckwalter

Hong-Ming Shieh

Michael Joseph Daley

Imre Kovesdi

Avner Yayon

Magdalena G Eisinger

Luyuan Li

The invention relates to Novel DNA and amino acid sequences for a heparin bending neurotrophic factor, (HBNF). Also described are expression vectors and host cells useful in a method for production of the HBNF protein.

Heparin binding neurotrophic factor gene sequence

The present invention relates to physiologically-active derivatized natural and recombinant mammalian and human proteins and polypeptides. The invention provides chemical methods for derivatizing natural and recombinantly-derived proteins or polypeptides containing cysteine residues, either naturally or through site specific mutageneses. The pharmaceutical compositions containing said derivatized proteins and/or polypeptides are formulated to provide stable, long-acting compositions of such proteins and/or polypeptides, previously difficult to achieve.

Stabilization of fibroblast growth factors by modification of cysteine

The present invention relates to physiologically-active derivatized natural and recombinant mammalian and human proteins and polypeptides. The invention provides chemical methods for derivatizing natural and recombinantly-derived proteins or polypeptides containing cysteine residues, either naturally or through site specific mutageneses. The pharmaceutical compositions containing the derivatized proteins and/or polypeptides are formulated to provide stable, long-acting compositions of such proteins and/or polypeptides, previously difficult to achieve.

Stabilization of somatotropins and other proteins by modification of

The invention relates to a method for inhibiting angiogenesis and proliferation of endothelial cells by administering an inhibitory amount of 7-�substituted amino!-9-�(substituted glycyl)amido!-6-demethyl-6-deoxytetracycline of Formula I: ##STR1## wherein R, R.sub.2, R.sub.3, and W are as defined in the specification. The invention also relates to a method for inhibiting proliferation of tumor cells and tumor growth by administering an inhibitory amount of a compound of Formula I in combination with a chemotherapeutic agent or radiation therapy. The invention also relates to compositions containing an effective inhibitory amount of a compound of Formula I in a pharmaceutically acceptable carrier.

Methods for inhibiting proliferation of tumor cells and tumor growth

The invention relates to a method for inhibiting angiogenesis and proliferation of endothelial cells by administering an inhibitory amount of a 7-�substituted amino!-9-�(substituted glycyl)amido!-6-demethyl-6-deoxytetracycline of Formula I: ##STR1## wherein R, R.sub.2, R.sub.3, and W are as defined in the specification. The invention also relates to a method for inhibiting proliferation of tumor cells and tumor growth by administering an inhibitory amount of a compound of Formula I in combination with a chemotherapeutic agent or radiation therapy. The invention also relates to compositions containing an effective inhibitory amount of a compound of Formula I in a pharmaceutically acceptable carrier.

Methods for inhibiting angiogenesis, proliferation of endothelial or

A group of growth factors, designated heparin-binding brain mitogens (HBBMs), is disclosed. The HBBMs are isolated from brain tissue by a sequence of purification steps. The growth factors may be useful in the promotion of angiogenesis, such as in the promotion of wound healing, bone healing and in the treatment of burns, as well as in promoting the formation, maintenance and repair of tissue, in particular, neural tissue.

Therapeutic compositions and methods for use of heparin-binding brain

The invention relates to a method for inhibiting angiogenesis and proliferation of endothelial cells by administering an inhibitory amount of a 7-halogen-9-[hydrogen or [(substituted glycyl)amido]]-6-demethyl-6-deoxytetracycline of Formula I: ##STR1## wherein X and W are as defined in the specification. The invention also relates to a method for inhibiting proliferation of tumor cells and tumor growth by administering an inhibitory amount of a compound of Formula I in combination with a chemotherapeutic agent or radiation therapy. The invention also relates to compositions containing an effective inhibitory amount of a compound of Formula I in a pharmaceutically acceptable carrier.

Methods for inhibiting angiogenesis proliferation of endothelial or

The invention relates to a method for inhibiting angiogenesis and proliferation of endothelial cells by administering an inhibitory amount of a 7-(hydrogen or di (C.sub.1 -C.sub.4)alkylamino)-8-halogen-9-(substituted)-6-demethyl-6-deoxytetracycl ine of Formula I: ##STR1## wherein R, X and W are as defined in the specification. The invention also relates to a method for inhibiting proliferation of tumor cells and tumor growth by administering an inhibitory amount of a compound of Formula I in combination with a chemotherapeutic agent or radiation therapy. The invention also relates to compositions containing an effective inhibitory amount of a compound of Formula I in a pharmaceutically acceptable carrier.

Method for inhibiting angiogenesis, proliferation of endothelial or

The invention relates to a method for inhibiting angiogenesis and proliferation of endothelial cells by administering an inhibitory amount of a 9-[(substituted glycyl)amido]-6-demethyl-6-deoxytetracycline of Formula I: ##STR1## wherein W, R.sub.2 and R.sub.3 are as defined in the specification. The invention also relates to a method for inhibiting proliferation of tumor cells and tumor growth by administering an inhibitory amount of a compound of Formula I in combination with a chemotherapeutic agent or radiation therapy. The invention also relates to compositions containing an effective inhibitory amount of a compound of Formula I in a pharmaceutically acceptable carrier.

Structural analogues of fibroblast growth factors have an amino acid sequence replacement in the ninth or tenth .beta.-strand of the factor, or the sequence that corresponds to the surface loop that connects the ninth and tenth .beta.-strands, such that the folding of the molecule is not significantly perturbed. Preferred analogues have the amino acid sequence replacement in the surface loop that extends from the ninth .beta.-strand to the tenth .beta.-strand and have the overall secondary and tertiary structure of the original factor, and bind to heparin and a member or members of the fibroblast growth factor receptor family with high affinity. In some embodiments, the analogues are prepared by replacing the surface loop sequence that connects the ninth and tenth .beta.-strand with another amino acid sequence such as a loop sequence from another structurally related fibroblast growth factor or an interleukin. Preferred analogues exhibit different biological properties and/or receptor binding specificity profiles from native factors.

Surface loop structural analogues of fibroblast growth factors

The present invention relates to novel fragments of basic fibroblast growth factor (bFGF). The mitogenic potency of one of these bFGF fragments, identified as HBF-2 is about 25-50 fold less than that of native bFGF but at least 10.sup.3 -10.sup.4 fold more active than that of previously reported synthetic fragments of bFGF. Therefore, the present invention provides the shortest fragment of bFGF that retains substantial biologic activity.

Active fragments of fibroblast growth factor

The present invention relates to novel chimeric fibroblast growth factors (FGF) wherein the alanine at amino acid 3 and serine 5 of native human recombinant basic fibroblast growth factor are replaced with glutamic acid. The N-terminus sequence of the present chimeric FGFs identify homology with that of human acidic fibroblast growth factor. The mitogenic properties of the native human recombinant basic FGF are exhibited by the present chimeric FGFs, and they are efficiently expressed in E. coli at significantly greater yields that previously reported. Novel variants of this new glu.sup.3,5 basic fibroblast growth factor, such as those in which cysteine 78 and cysteine 96 are replaced, e.g., with serine or other amino acids, to produce stabilized versions of the glu.sup.3,5 basic FGF and eliminate disulfide scrambled forms, are also described.

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Peekskill, NY, United States of America

Peter Bohlen