| United States Patent | 5,496,712 |
| Cappello, et. al. | Mar. 5, 1996 |
| Inventors: | Cappello; Joseph (San Diego, CA); Ferrari; Franco A. (La Jolla, CA). |
| Assignee: | Protein Polymer Technologies, Inc. (San Diego, CA). |
| Appl. No.: | 972,032 |
| Filed: | Nov. 5, 1992 |
| Continuation-in-part of Ser No. 791,960, Nov. 12, 1991, abandoned, which is a continuation-in-part of Ser. No. 609,716, Nov. 6, 1990. |
| Intl. Cl. : | C12P 21/02, C12N 15/12, C07K 14/245, C07K 14/47 |
| Current U.S. Cl.: | 435/69.1; 435/252.33; 530/356; 530/388.9; 530/389.8; 536/23.5 |
| Field of Search: | 435/69.1, 252.33; 536/23.5; 530/354, 356, 388.9, 389.8 |
| 8803533 | Nov., 1986 | WO | |
| 8805082 | Dec., 1987 | WO | |
| 9005177 | Nov., 1988 | WO |
I. Goldberg, et al. (1989) Gene 80:305-314. Cloning and expression of a collagen-analog-encoding synthetic gene in E. coli.
T. Kempe, et al. (1985) Gene 39:239-245. Multiple copy genes: production and modification of monomeric peptides from large multimeric fusion proteins.
M. Lennick, et al. (1987) Gene 61:103-112. High-level expression of a-human atrial natriuretic peptide from multiple joined genes in E. coli.
W. Taylor and P. Hagerman (1987) Gene 53:139-144. A general method for cloning DNA fragments in multiple copies.
L. Aslund, et al. (1987) Proc. Natl. Acad. Sci., USA 84:1399-1403. Synthetic gene contruct expressing a repeated and highly immunogenic epitope of the P. falciparum antigen Pf1155.
M. Schulz, et al. (1987) J. Bact. 169:5385-5392. Increased expression in E. coli of a synthetic gene encoding human somatomedin C after gene duplication and fusion.
S. Kim and W. Szybalski (1988) Gene 7:1-8. Amplifiation of cloned DNA as tandem multimers using BspM1-generated asymmetric cohesive ends.
S. Takeshita, et al. (1988) Gene 71:9-18. Tandem gene amplification in vitro for rapid and efficient expression in animal cells.
G. Bressan, et al. (1987) Biochemistry 26:1497-1503. Repeating structure of chick tropoelastin revealed by complementary DNA cloning.
S. Shen (1984) Proc. Natl. Acad. Sci., USA 81:4627-4631. Multiple joined genes prevent product degradation in E. coli.
M. Doel, et al. (1980) Nuc. Acids Res. 8:4575-4592. The expression in E. coli of synthetic repeating polymeric genes coding for poly)L-aspartyl-L-phenylalanine).
J. Hartley, et al. (1981) Gene 13:347-353. Cloning multiple copies of a DNA segment.
J. Sadler, et al. (1980) Gene 8:279-300. Plasmids containing many tandem copies of a synthetic lactose operator.
Miller, E. J. (1985) Ann. N.Y. Acad. Sci. 460, 1-13.
Fleishmajer, et al. Collagen fibrillogenesis in human skin. Annals of the New York Academy of Sciences 260:246-257 (1985).
Primary Examiner: Patterson, Jr.; Charles L.
Attorney, Agent or Firm: Rowland; Bertram I.
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.
