Osteogenic proteins

An isolated protein comprising the amino acid sequence described by residues 335 to 431 of Seq. ID No. 1 (OPS).

An isolated protein comprising the amino acid sequence described by residues 334 to 430 of Seq. ID No. 24.

An isolated protein comprising the amino acid sequence described by residues 303 to 399 of Seq. ID No. 26.

An isolated protein comprising the amino acid sequence described by residues 306 to 402 of Seq. ID No. 28.

Osteogenic protein expressed from recombinant DNA in a host cell,

• the protein comprising a pair of oxidized subunits disulfide bonded to produce a dimeric species, one of said subunits having an amino acid sequence sufficiently duplicative of the sequence comprising residues 335 to 431 of Seq. ID No. 1 (OPS),
• such that the disulfide bonded dimeric species comprising said subunit has a conformation capable of inducing cartilage and endochondral bone formation in a mammal when disposed within a matrix implanted in said mammal.

Osteogenic protein expressed from recombinant DNA in a host cell,

• the protein comprising a pair of oxidized subunits disulfide bonded to produce a dimeric species, having a conformation capable of inducing cartilage and endochondral bone formation in a mammal when disposed within a matrix implanted in said mammal,
• one of said subunits having an amino acid sequence encoded by a nucleic acid capable of hybridizing to a nucleic acid encoding OPS (res. 335-431, Seq. ID No. 1) under stringent hybridization conditions.

Osteogenic protein expressed from recombinant DNA in a host cell, the protein comprising a pair of oxidized subunits disulfide bonded to produce a dimeric species having a conformation capable of inducing cartilage and endochondral bone formation in a mammal when disposed within a matrix implanted in said mammal,

• one of said subunits having an amino acid sequence comprising OPS (residues 335 to 431 of Seq. ID No. 1), including mutated forms thereof, allelic variants thereof, truncated forms thereof and biosynthetic analogs thereof.

A dimeric protein expressed from a nucleic acid encoding an amino acid sequence sufficiently duplicative of the amino acid sequence encoded by the DNA sequence of Seq. ID No. 1 or Seq. ID No. 3 such that, when said protein is oxidized to produce a disulfide bonded dimeric species, the dimeric species has a conformation that is capable of inducing endochondral bone and cartilage formation when disposed within a matrix and implanted in a mammal.

An osteogenic protein expressed from recombinant DNA in a mammalian host cell and capable of inducing endochondral bone formation in a mammal when disposed within a matrix implanted in said mammal,

• the protein comprising two oxidized subunits, the amino acid sequence of each subunit being sufficiently duplicative of the amino sequence described by residues 335 to 431 of Seq. ID No. 1 (OPS) such that the dimeric species comprising said subunits has a conformation that is capable of inducing endochondral bone formation in a mammal when disposed within said matrix and implanted in said mammal.

An isolated polypeptide chain useful as a subunit of a dimeric osteogenic protein, said polypeptide chain having an amino acid sequence sharing greater than 74% identity with the sequence described by residues 264-402 of Seq. ID No. 28 (hOP2-Ala) such that the disulfide bonded dimeric species comprising said polypeptide chain is capable of inducing endochondral bone formation when implanted in a mammal in association with a matrix.

An isolated polypeptide chain useful as a subunit of a dimeric osteogenic protein having a conformation capable of inducing endochondral bone formation in a mammal when implanted in a mammal in association with a matrix,

• said polypeptide chain having an amino acid sequence encoded by a nucleic acid capable of hybridizing to a nucleic acid encoding the pro region of mOP2-PP (res. 17-260 of Seq. ID No. 26) or hOP2-PP (res. 17-263 of Seq. ID No. 28) under stringent hybridization conditions.

An isolated osteogenic protein comprising a pair of oxidized subunits disulfide bonded to produce a dimeric species, one of said subunits comprising a polypeptide chain having an amino acid sequence comprising the sequence OPX-7C (Seq. ID No. 31), wherein each Xaa independently represents one of the 20 naturally occurring L-isomer, .alpha.-amino acids or a derivative thereof, and together with said 7 cysteine residues define said polypeptide chain,

• such that the dimeric species comprising said subunit has a conformation capable of inducing endochondral bone formation in a mammal when implanted in said mammal in association with a matrix.

An isolated protein comprising a pair of oxidized subunits disulfide bonded to produce a dimeric species, one of said subunits comprising a polypeptide chain having an amino acid sequence comprising OPX (Seq. ID No. 30) such that the dimeric species comprising said subunit has a conformation capable of inducing cartilage and endochondral bone formation in a mammal when implanted in said mammal in association on with a matrix.

A protein expressed from recombinant DNA in a host cell, said protein comprising an amino acid sequence encoded by a nucleic acid capable of hybridizing to a nucleic acid encoding residues 306-402 of hOP2 (Seq. ID No. 28) under stringent hybridization conditions.