| United States Patent | 5,773,249 |
| Cappello, et. al. | Jun. 30, 1998 |
| Inventors: | Cappello; Joseph (San Diego, CA); Ferrari; Franco A. (La Jolla, CA). |
| Assignee: | Protein Polymer Technologies, Inc. (San Diego, CA). |
| Appl. No.: | 642,255 |
| Filed: | May 2, 1996 |
| Intl. Cl. : | C12P 21/02, C07K 14/435, C12N 15/12 |
| Current U.S. Cl.: | 435/69.1; 435/69.7; 435/252.3; 435/252.33; 530/356; 530/388.9; 530/389.8; 536/23.5 |
| Field of Search: | 530/356, 350, 388.9, 389.8; 536/93.5; 435/252.3, 252.33, 69.1, 69.7 |
| WO/8803533 | May, 1988 | WO | |
| WO/8805082 | Jul., 1988 | WO | |
| WO/9005177 | Nov., 1988 | WO |
Goldberg et al., "Cloning and Expression of a Collagen-Analog-Encoding Synthetic Gene in E. coli", Gene (1989), 80:305-314.
Kempe et al., "Multiple Copy Genes: Production and Modification of Monomeric Peptides From Large Multimeric Fusion Proteins", Gene (1985), 39:239-245.
Lennick et al., "High-Level Expression of A-Human Atrial Natriuretic Peptide From Multiple Joined Genes in E. coli", Gene (1987), 61:103-112.
Taylor and Hagerman, "A General Method for Cloning DNA Fragments in Multiple Copies", Gene (1987), 53:139-144.
Aslund et al., "Synthetic Gene Contruct Expression a Repeated and Highly Immunogenic", PNAS (1987), 84:1399-1403.
Schulz et al., "Increased Expression in E. coli of a Synthetic Gene Encoding Human Somatomedin C After Gene Duplication and Fusion", J. Bact. (1987), 169:5385-5392.
Kim and Szybalski, "Amplification of Cloned DNA as Tandem Multimers Using BspM1-Generated Asymmetric Cohesive Ends", Gene (1988), 7:1-8.
Takeshita et al., "Tandem Gene Amplification In Vitro for Rapid and Efficient Expression in Animal Cells", Gene (1988), 71:9-18.
Bressan et al., "Repeating Structure of Chick Tropoelastin Revealed By Complentary DNA Cloning", Biochemistry (1987), 26:1497-1503.
Shen, "Multiple Joined Genes Prevent Product Degradation in E. coli.", PNAS (1984), 81:4627-4631.
Doel et al., "The Expression in E. coli of Synthetic Repeating Polymeric Genes Coding for Poly)L-aspartyl-L-phenylalanine", Nucl. Acids. Res (1980), 8:4575-4592.
Hartley et al., "Cloning Multiple Copies of a DNA Segment", Gene (1981), 13:347-353.
Sadler et al., "Plasmids Containing Many Tandem Copies of a Synthetic Lactose Operator", Gene (1980), 8:279-300.
Fleishmajer et al., "Collagen Fibrillogenesis in Human Skin", Annals of the New York Academy of Sciences (1985), 260:246-257.
Miller, E.J. (1985) Ann. N.Y. Acad. Sci. 460,1-13.
Primary Examiner: Patterson, Jr.; Charles L.
Attorney, Agent or Firm: Flehr Hohbach Test Albritton and Herbert
LLPTrecartin; Richard F., Kresnak; Mark T.
Collagen-like polymers having repetitive triads are produced having reduced proline content, where glycine is the initial amino acid and the subsequent amino acids are varied, while retaining at least a minimum percentage of prolines. The resulting polymers have collagen-like properties, but are capable of being produced in unicellular microorganisms at high molecular weights and in high efficiency. The polymers, while retaining collagen-like characteristics, include various novel sequences which impart new characteristics, finding wide use in photographic, medical, structural and fiber applications.
