Chiron Corporation

Nordisk Gentofte

Novo Nordisk A/s

Novartis Vaccines & Diagnostics, Gmbh

Frank R Masiarz

Denis J Gospodarowicz

Michael C Kiefer

George Kuo

Pablo D Valenzuela

Martha Truett

Mirella Ezban Rasmussen

Jennifer M Favaloro

Philip J Barr

Rae Lyn Burke

Carol A Pachl

Daniel Caput

Walter Hans Born

Jurgen Johann Zapf

The present invention relates to a keratinocyte growth factor fragment, KGF, or an analog thereof that is composed of a portion of an amino acid sequence of mature, full length keratinocyte growth factor, KGF. The fragment exhibits at least a 2-fold increase in mitogenic activity as compared to a mature, recombinant keratinocyte growth factor, rKGF, but lacks a sequence comprising the first 23 amino acid residues, C-N-D-M-T-P-E-Q-M-A-T-N-V-N-C-S-S-P-E-R-H-T-R- (SEQ ID NO: 2) of the KGFN-terminus. The present invention also relates to a DNA molecule encoding KGF, an expression vector and a transformed host containing the DNA molecule, and a method of producing KGFby culturing the transformed host. The present invention further relates to a conjugate of KGFand a toxin molecule, and the use thereof for treatment of hyperproliferative disease of the epidermis. Moreover, the present invention relates to a therapeutic composition containing KGFand a pharmaceutically acceptable carrier and the use thereof for wound healing purposes.

Truncated keratinocyte growth factor (KGF) having increased biological activity

Methods and compositions are provided for recombinant DNA production of Factor VIIIC and truncated derivatives thereof. Based on amino acid sequences, probes are developed for isolating messenger RNA, cDNA and/or chromosomal DNA encoding for Factor VIIIC. The Factor VIIIC gene in its entirety, a fragment thereof, or a cDNA is then used for expression of Factor VIIIC in a host. The bacteriophage &#x3bb;FVIII23D containing the 14.43 kb EcoRI fragment was deposited at the A.T.C.C. on Jan. 4, 1984 and given Accession No. 40094. Also, the vector pSVF8-200 was deposited at the A.T.C.C. on Jul. 17, 1985 and given Accession No. 40190.

Factor VIII:C nucleic acid molecules

The present invention relates to a keratinocyte growth factor fragment, KGF, or an analog thereof that is composed of a portion of an amino acid sequence of mature, full length keratinocyte growth factor, KGF. The fragment exhibits at least a 2-fold increase in mitogenic activity as compared to a mature, recombinant keratinocyte growth factor, rKGF, but lacks a sequence comprising the first 23 amino acid residues; C-N-D-M-T-P-E-Q-M-A-T-N-V-N-C-S-S-P-E-R-H-T-R- (SEQ ID NO: 2) of the KGFN-terminus. The present invention also relates to a DNA molecule encoding KGF, an expression vector and a transformed host containing the DNA molecule, and a method of producing KGFby culturing the transformed host. The present invention further relates to a conjugate of KGFand a toxin molecule, and the use thereof for treatment of hyperproliferative disease of the epidermis. Moreover, the present invention relates to a therapeutic composition containing KGFand a pharmaceutically acceptable carrier and the use thereof for wound healing purposes.

The present invention relates to a keratinocyte growth factor fragment, KGF , or an analog thereof that is composed of a portion of an amino acid sequence of mature, full length keratinocyte growth factor, KGF . The fragment exhibits at least a 2-fold increase in mitogenic activity as compared to a mature, recombinant keratinocyte growth factor, rKGF, but lacks a sequence comprising the first 23 amino acid residues. C-N-D-M-T-P-E-Q-M-A-T-N-V-N-C-S-S-P-E-R-H-T-R- (SEQ ID NO: 2) of the KGF N-terminus. The present invention also relates to a DNA molecule encoding KGF , an expression vector and a transformed host containing the DNA molecule, and a method of producing KGF by culturing the transformed host. The present invention further relates to a conjugate of KGF and a toxin molecule, and the use thereof for treatment of hyperproliferative disease of the epidermis. Moreover, the present invention relates to a therapeutic composition containing KGF and a pharmaceutically acceptable carrier and the use thereof for wound healing purposes.

The present invention relates to keratinocyte growth factor fragment, KGF.sub.des1-23, or an analog thereof that is composed of a portion of an amino acid sequence of mature, full length keratinocyte growth factor, KGF.sub.163. The fragment exhibits at least a 2-fold increase in mitogenic activity as compared to a mature, recombinant keratonocyte growth factor, rKGF, but lacks a sequence comprising the first 23 amino acid residues, C-N-D-M-T-P-E-Q-M-A-T-N-V-N-C-S-S-P-E-R-H-T-R-(SEQ ID NO: 2) of the KGF.sub.163 N-terminus. The present invention also relates to a DNA molecule encoding KGF.sub.des1-23, an expression vector and a transformed host containing the DNA molecule, and a method of producing KGF.sub.des1-23 by culturing the transformed host. The present invention further relates to a conjugate of KGF.sub.des1-23 and a toxin molecule, and the use thereof for treatment of hyperproliferative disease of the epidermis. Moreover, the present invention relates to a therapeutic composition containing KGF.sub.des1-23 and a pharmaceutically acceptable carrier and the use thereof for wound healing purposes.

Truncated keratinocyte growth factor (KGF) having increased biological

A purified binding protein selected from the group consisting of insulin-like growth factor binding protein having an amino acid sequence which is at least 85% homologous to the amino acid sequence of FIG. 1 and fragments thereof comprising at least 10 consecutive amino acids of the sequence that are capable of binding to an antibody specific for the protein or to an insulin-like growth factor is described. Recombinant DNA molecules encoding the binding proteins and subsequences thereof are also described along with recombinant microorganisms and cell lines containing the DNA molecules and methods for preparing the binding proteins by growing the recombinant hosts containing the relevant DNA molecules. Antibodies to the protein, identified as IGFBP-6, which are useful in various diagnostic applications, are also described.

Insulin-like growth factor binding protein (IGFBP-6)

Antibodies to insulin-like growth factor binding protein IGFBP-6

The present invention relates to a keratinocyte growth factor fragment, KGF.sub.des1-23, or an analog thereof that is composed of a portion of an amino acid sequence of mature, full length keratinocyte growth factor, KGF.sub.163. The fragment exhibits at least a 2-fold increase in mitogenic activity as compared to a mature, recombinant keratinocyte growth factor, rKGF, but lacks a sequence comprising the first 23 amino acid residues, C-N-D-M-T-P-E-Q-M-A-T-N-V-N-C-S-S-P-E-R-H-T-R- (SEQ ID NO: 2) of the KGF.sub.163 N-terminus. The present invention also relates to a DNA molecule encoding KGF.sub.des1-23, an expression vector and a transformed host containing the DNA molecule, and a method of producing KGF.sub.des1-23 by culturing the transformed host. The present invention further relates to a conjugate of KGF.sub.des1-23 and a toxin molecule, and the use thereof for treatment of hyperproliferative disease of the epidermis. Moreover, the present invention relates to a therapeutic composition containing KGF.sub.des1-23 and a pharmaceutically acceptable carrier and the use thereof for wound healing purposes.

The present invention relates to a keratiniocyte growth factor fragment, KGF.sub.des1-23, or an analog thereof that is composed of a portion of an amino acid sequence of mature, full length keratinlocyte growth factor, KGF.sub.163. The fragment exhibits at least a 2-fold increase in mitogenic activity as compared to a mature, recombinant keratinocyte growth factor, rKGF, but lacks a sequence comprising the first 23 amino acid residues, C-N-D-M-T-P-E-Q-M-A-T-N-V-N-C-S-S-P-E-R-H-T-R- (SEQ ID NO: 2) of the KGF.sub.163 N-terminus. The present invention also relates to a DNA molecule encoding KGF.sub.des1-23, an expression vector and a transformed host containing the DNA molecule, and a method of producing KGF.sub.des1-23 by culturing the transformed host. The present invention further relates to a conjugate of KGF.sub.des1-23 and a toxin molecule, and the use thereof for treatment of hyperproliferative disease of the epidermis. Moreover, the present invention relates to a therapeutic composition containing KGF.sub.des1-23 and a pharmaceutically acceptable carrier and the use thereof for wound healing purposes.

Methods of wound healing and treating hyperproliferative diseases of

Methods and compositions are provided for recombinant DNA production of Factor VIIIC and truncated derivatives thereof. Based on amino acid sequences, probes are developed for isolating messenger RNA and/or chromosomal DNA encoding for Factor VIIIC. The Factor VIIIC gene in its entirety or encoding for a fragment thereof is then used for expression of Factor VIIIC in a host. The bacteriophage .lambda.FVIII23D containing the 14.43 kb EcoRI fragment was deposited at the A.T.C.C. on Jan. 4, 1984 and given Accession No. 40094.

Method and composition for preparation of factor VIIIC

The present invention relates to a keratinocyte growth factor fragment, KGF.sub.des1-23, or an analog thereof that is composed of a portion of an amino acid sequence of mature, full length keratinocyte growth factor, KGF.sub.163. The fragment exhibits at least a 2-fold increase in mitogenic activity as compared to a mature, recombinant keratinocyte growth factor, rKGF, but lacks i sequence comprising the first 23 amino acid residues, C-N-D-M-T-P-E-Q-M-A-T-N-V-N-C-S-S-P-E-R-H-T-R-(SEQ ID NO: 2) of the KGF.sub.163 N-terminus. The present invention also relates to a DNA molecule encoding KGF.sub.des1-23, an expression vector and a transformed host containing the DNA molecule, and a method of producing KGF.sub.des1-23 by culturing the transformed host The present invention further relates to a conjugate of KGF.sub.des1-23 and a toxin molecule, and the use thereof for treatment of hyperproliferative disease of the epidermis. Moreover, the present invention relates to a therapeutic composition containing KGF.sub.des1-23 and a pharmaceutically acceptable carrier and the use thereof for wound healing purposes.

Conjugates comprising truncated keratinocyte growth factor (KGF) having

The isolation, identification and production by recombinant methods of bone calcification factor, a 22 KD polypeptide, are disclosed. The peptide has calcification-inducing activity when implanted with matrix Gla protein into mammals.

Bone calcification factor and recombinant production of the factor

The purification and cloning of bone morphogenetic proteins are disclosed, as well as production of BMP and its analogs thereof by recombinant DNA techniques. Pharmaceutical compositions comprising BMP and the use of such compositions are also disclosed.

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San Francisco, CA, United States of America

Frank R Masiarz