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Stability, Characterization, Formulation, and Delivery System Development for Transforming Growth Factor-Beta1

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Formulation, Characterization, and Stability of Protein Drugs: Case Histories

Part of the book series: Pharmaceutical Biotechnology ((PBIO,volume 9))

Conclusions

This chapter has reviewed the multifunctional role that the TGF-β play with diverse proliferative and suppressive effects on many different cell types. The various in vitro and in vivo effects of TGF-β was discussed with emphasis on the therapeutic potential of this growth factor in areas such as wound healing and bone regeneration. The structure and properties of TGF-β were presented, followed by a more detailed description of the characterization and stabilization of TGF-β 1) in both the liquid and lyophilized state. The chapter concluded with a review of some of the different controlled release systems that have been utilized for the delivery of TGF-β 1 to various preclinical models. Clearly the therapeutic potential for TGF-β 1) is great. Both the formulation and delivery of this growth factor will play an important role in its eventual clinical success

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References

  • Amman, A. J., Beck, L. S., DeGuzman, L., Hirabayashi, S. E., Lee, W. P., McFatridge, L., Nguyen, T., Xu, Y., and Mustoe, T. A., 1990, Transforming growth factor beta. Effect on soft tissue repair, Ann. N.Y. Acad. Sci. 593:124–134.

    Article  Google Scholar 

  • Anzano, M. A., Roberts, A. B., De Larco, J. E., Wakefield, L. M., Assoian, R. K., Roche, N. S., Smith, J. M., Lazarus, J. E., and Sporn, M. B., 1985, Increased secretion of type beta transforming growth factor accompanies viral transformation of cells, Mol Cell. Biol. 5:242–247.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Arakawa, T., and Timasheff, S. N., 1982, Stabilization of protein structure by sugars, Biochemistry 26: 7813–7818.

    Google Scholar 

  • Assoian, R. K., Komoriya, A., Meyers, C. A., Miller, D. M., and Sporn, M. B., 1983, Transforming growth factor beta in human platelets. Identification of a major storage site, purification and characterization, J. Biol. Chem. 258:7155–7160.

    CAS  PubMed  Google Scholar 

  • Beck, S. L., Chen, T. L., Hirabayashi, S. E., Deguzman, L., Lee, W. P., McFatridge, L. A., Xu, Y., Bates, R. L., and Ammann, A. J., 1990a, Accelerated healing of ulcer wounds in the rabbit ear by recombinant human transforming growth factor beta 1, Growth Factors 2:273–282.

    Article  CAS  PubMed  Google Scholar 

  • Beck, S. L., Chen, T. L., Mikalauski, P., and Ammann, A. J., 1990b, Recombinant human transforming growth factor beta1 rhTGF-β 1 enhances healing and strength of granulation skin wounds, Growth Factors 3:267–275.

    Article  CAS  PubMed  Google Scholar 

  • Beck, S. L., Deguzman, L., Lee, W. P., Xu, Y., McFatridge, L. L., and Amento, E. P., 1991a, TGF-β 1 accelerates wound healing: Reversal of steroid-impaired healing in rats and rabbits, Growth Factors 6:295–304.

    Article  Google Scholar 

  • Beck, S. L., Deguzman, L., Lee, W. P., McFatridge, L. L., Gillett, N. A., and Amento, E. P., 1991b, TGF-β 1) induces bone closure of skull defects, J. Bone Miner. Res. 6:1257–12

    Article  CAS  PubMed  Google Scholar 

  • Brown, G. L., Curtsinger, L. J., White, M, Mitchell, R. O., Pietsch, J., Nordquist, R., vonFraunhofer, A., and Schultz, G. S., 1988, Acceleration of tensile strength of incisions treated with EGF and TGF-β, Ann. Surg. 208:788–793.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cate, R. L., Mattaliano, R. J., Hession, C., Tizard, R., Farber, N. M., Cheung, A., Ninfa, E. G., Frey, A. Z., Gash, D. J., and Chow, E. P., 1986, Isolation of the bovine and human genes for Mullerian inhibiting substance and expression of the human gene in animal cells, Cell 45:685–698.

    Article  CAS  PubMed  Google Scholar 

  • Chang, B. S., and Randall, C. S., 1992, Use of subambient thermal analysis to optimize protein lyophilization, Cryobiology 29:632–656.

    Article  CAS  Google Scholar 

  • Curtsinger, L. J., Pietsch, J. D., Brown, G. L., von Fraunhofer, A., Ackerman, D., Polk, H. C., and Schultz, G. S., 1989, Reversal of adriamycin-impaired wound healing by transforming growth factor-beta, Surg., Gynecol. Obstet. 168:517–522.

    CAS  Google Scholar 

  • Daopin, S., Piez, K. A., Ogawa. Y., and Davies, D. R., 1992, Crystal structure of transforming growth factorβ 2 An unusual fold for the superfamily, Science 257:369–373.

    Article  CAS  PubMed  Google Scholar 

  • Frolik, C. A., Wakefield, L. M., Smith, D. M., and Sporn, M. B., 1984, Characterization of a membrane receptor for transforming growth factor-beta in normal rat kidney fibroblasts, J. Biol. Chem. 259: 10995–11000.

    CAS  PubMed  Google Scholar 

  • Geigert, J., 1989, Overview of the stability and handling of recombinant protein drugs, J. Parent. Sci. Technol. 43:220–224.

    CAS  Google Scholar 

  • Gentry, L. E., Lioubin, M. N., Purchio, A. F., and Marquardt, H., 1988, Molecular events in the processing of recombinant type I pre-pro-transforming growth factor beta to the mature polypeptide, Mol. Cell. Biol. 8:4162–4168.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Glaser, B. M., Michels, R. G., and Kuppermann, B. D., 1992, Transforming growth factor-2 for the treatment of full-thickness macular holes. A prospective randomized study, Opthamology 99:1162–1173.

    Article  CAS  Google Scholar 

  • Gombotz, W. R., Pankey, S. C., Bouchard, L. S., Phan, D. H., and Puolakkainen, P. A., 1994, Stimulation of bone healing by transforming growth factor-beta, released from polymeric or ceramic implants, J. Appl. Biomater. 5:141–150.

    Article  CAS  PubMed  Google Scholar 

  • Gombotz, W. R., Pankey, S. C., Bouchard, L. S., Ranchalis, J., and Puolakkainen, P., 1993, Controlled release of TGF-β 1 from a biodegradable matrix for bone regeneration, J. Biomater. Sci. Polym. Ed. 5: 49–63.

    Article  CAS  PubMed  Google Scholar 

  • Heine, U. I., Munoz, E. F., Flanders, K. C., Ellingsworth, L. R., Lam, H. Y., Thompson, N. L., Roberts, A. B., and Sporn, M. B., 1987, Role of transforming growth factor beta in the development of the mouse embryo, J. Cell Biol. 105:2861–2876.

    Article  CAS  PubMed  Google Scholar 

  • Ignotz, R. A., and Massague, J., 1985, Type beta transforming growth factor controls the adipogenic differentiation of 3T3 fibroblasts, Proc. Natl. Acad. Sci. 82:8530–8534.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ikeda, T., Lioubin, M. N., and Marquardt, H., 1987, Human transforming growth factor type 2: Production by a prostatic adenocarcinoma cell line, purification and initial Characterization, Biochemistry 26:2406–2410.

    Article  CAS  PubMed  Google Scholar 

  • Jones, S. C., Curtsinger, L. J., Whalen, J. D., Pietsch, J. D., Ackerman, D., Brown, G. L., and Schultz, G. S., 1991, Effect of topical recombinant TGF-β on healing of partial thickness injuries, J. Surg. Res. 51: 344–352.

    Article  CAS  PubMed  Google Scholar 

  • Joyce, M. E., Roberts, A. B., Sporn, M. B., and Bolander, M. E., 1990, Transforming growth factor-and the initiation of chondrogenesis and osteogenesis in the rat femur, J. Cell Biol. 110:2195–2207.

    Article  CAS  PubMed  Google Scholar 

  • Keski-Oja, J., Lyons, R. M., and Moses, H. L., 1987, Inactive secreted form(s) of transforming growth factor-β (TGFβ) Activation by proteolysis, J. Cell. Biochem. (Suppl.) 11A:60.

    Google Scholar 

  • Kibblewhite, D. J., Bruce, A. G., Strong, D. M., Ott, S. M., Purchio, A. F., and Larrabee, W. F., 1993, Transforming growth factor-beta accelerates osteoinduction in a craniofacial onlay model, Growth Factors 9:185–193.

    CAS  PubMed  Google Scholar 

  • Kurokawa, M., Lynch, K., and Podolsky, D. K., 1987, Effects of growth factors on an intestinal epithelial cell line: Transforming growth factor beta inhibits proliferation and stimulates differentiation, Biochem. Biophys. Res. Commun. 142:775–782.

    Article  Google Scholar 

  • Kuruvilla, A. P., Shah, R., Hochwald, G. M., Liggitt, H. D., Palladino, M. A., and Thorbecke, G. J., 1991, Protective effect of transforming growth factor 1 on experimental autoimmune diseases in mice, Proc. Natl. Acad. Sci. 88:2918–2921.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lawrence, D. A., Pircher, R., and Jullien, P., 1985, Conversion of a high molecular weight latent beta-TGF from chicken embryo fibroblasts into a low molecular weight active beta-TGF under acidic conditions, Biochem. Biophys. Res. Commun. 133:1026–1034.

    Article  CAS  PubMed  Google Scholar 

  • Lefer, A. M., Tsao, P., Aoki, N., and Palladino, M. A., 1990, Mediation of cardioprotection by transforming growth factor-beta, Science 249:61–64.

    Article  CAS  PubMed  Google Scholar 

  • Ling, N., Ying, S. Y., Ueno, N., Shimasaki, S., Esch, F., Hotta, M., and Guillemin, R., 1986, Pituitary FSH is released by a heterodimer of the beta-subunits from the two forms of inhibin, Nature 321:779–782.

    Article  CAS  PubMed  Google Scholar 

  • Lioubin, M. N., Madisen, L., and Marquardt, H., 1991, Characterization of latent recombinant TGF-β 2 produced by Chinese hamster ovary cells, J. Cell. Biochem. 45:112–121.

    Article  CAS  PubMed  Google Scholar 

  • Lyons, R. M., Keski-Oja, J., and Moses, H. L., 1988, Proteolytic activation of latent transforming growth factor-beta from fibroblast-conditioned medium, J. Cell. Biol. 106:1659–1665.

    Article  CAS  PubMed  Google Scholar 

  • Mackie, E. J., and Trechsel, U., 1990, Stimulation of bone formation in vivo by transforming growth factor-β remodeling of woven bone and lack of inhibition by indomethacin. Bone 11:295–300.

    Article  CAS  PubMed  Google Scholar 

  • Madri, J. A., Pratt, B. M., and Tucker, A., 1988, Phenotypic modulation of endothelial cells by transforming growth factor-β depends upon the composition and organization of the extracellular matrix, 7. Cell Biol. 106:1375–1384.

    Article  CAS  Google Scholar 

  • Marcelli, C., Yates, A. J., and Mundy, G. R., 1990, in vivo effects of human recombinant transforming growth factor β on bone turnover in normal mice, J. Bone Miner. Res. 5:1087–1096.

    Article  CAS  PubMed  Google Scholar 

  • Marquardt, H., Lioubin, M. N., and Ikeda, T., 1987, Complete amino acid sequence of human transforming growth factor type β 2, J. Biol. Chem. 262:12127–121

    CAS  PubMed  Google Scholar 

  • Mason, A. J., Hayflick, J. S., Ling, N., Esch, F., Ueno, N., Ying, S. Y., Guillemin, R., Niall, H., and Seeburg, P. H., 1985, Complementary DNA sequences of ovarian follicular inhibin show precursor structure and homology with transforming growth factor-beta, Nature 318:659–663.

    Article  CAS  PubMed  Google Scholar 

  • Massague, J., 1985, Subunit structure of a high-affinity receptor for type beta-transforming growth factor. Evidence for a disulfide-linked glycosylated receptor complex, J. Biol. Chem. 260:7059–7066.

    CAS  PubMed  Google Scholar 

  • Masui, T., Wakefield, L. M., Lechner, J. F., LaVeck, M. A., Sporn, M. B., and Harris, C. C., 1986, Type beta transforming growth factor is the primary differentiation-inducing serum factor for normal human bronchial epithelial cells, Proc. Natl. Acad. Sci. 83:2438–2442.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Miller, D. A., Pelton, R. W., Derynk, R., and Moses, H. A., 1990, Transforming growth factor-β a family of growth regulatory proteins, Ann. N.Y. Acad. Sci. 593:208–217.

    Article  CAS  PubMed  Google Scholar 

  • Miyazono, K., Hellman, U., Wernstedt, C., and Helin, C. H., 1988, Latent high molecular weight complex of transforming growth factor beta 1. Purification from human platelets and structural characterization, J. Biol. Chem. 263:6407–6415.

    CAS  PubMed  Google Scholar 

  • Moses, H. L., Tucker, R. F., Leof, E. B., Coffey, R. J., Halper, J., and Shipley, G. D., 1985, Type-β transforming growth factor is a growth stimulator and growth inhibitor, Cancer Cells 3:65–71.

    CAS  Google Scholar 

  • Mumper, R. J., Hoffman, A. S., Puolakkainen, P. A., Bouchard, L. S., and Gombotz, W. R., 1994, Calciumalginate beads for the oral delivery of transforming growth factor-β 1 (TGF-β 1); stabilization of TGF-β 1 by the addition of polyacrylic acid within acid-treated beads, J. Control. Rel. 30:241–251.

    Article  CAS  Google Scholar 

  • Mustoe, T. A., Pierce, G. F., Thomason, A., Gramates, P., Sporn, M. B., and Deuel, T. F., 1987, Accelerated healing of incisional wounds in rats induced by transforming growth factor β, Science 237:1333–1336.

    Article  CAS  PubMed  Google Scholar 

  • Nilsen-Hamilton, M., 1990, Transforming growth factor beta and its actions on cellular growth and differentiation, Curr. Top. Dev. Biol. 24:95–136.

    Article  CAS  PubMed  Google Scholar 

  • Noda, M., and Camilliere, J. J., 1989, In vivo stimulation of bone formation by transforming growth factor-β Endocrinology 124:2991–2995.

    Article  CAS  PubMed  Google Scholar 

  • Piez, K. A., and Sporn, M. B., 1990, Transforming growth factor-βs, chemistry, biology and therapeutics, Ann. N. Y. Acad. Sci. 593.

    Google Scholar 

  • Pikal, M. J., Dellerman, K. M., Roy, M. L., and Riggin, R. M., 1991, The effects of formulation variables on the stability of freeze-dried human growth hormone, Pharm. Res. 8:427–436.

    Article  CAS  PubMed  Google Scholar 

  • Pircher, R., Jullien, P., and Lawrence, D. A., 1986, Beta-transforming growth factor is stored in human blood platelets as a latent high molecular weight complex, Biochem. Biophys. Rex. Commun. 136:30–37.

    Article  CAS  Google Scholar 

  • Puolakkainen, P. A., Ranchalis, J. E., Gombotz, W. R., Hoffman, A. S., Mumper, R. J., and Twardzik, D. R., 1994, Novel delivery system for inducing quiescence in intestinal stem cells in rats by transforming growth factor β 1, Gastroenterology 107:1319–13

    Article  CAS  PubMed  Google Scholar 

  • Puolakkainen, P., and Twardzik, D. R., 1993, Transforming growth factors alpha and beta, in: Neurotrophic Factors (S. E. Loughlin and J. H. Fallon, eds.). Academic Press, San Diego, pp. 359–389.

    Google Scholar 

  • Puolakkainen, P. A., Twardzik, D. R., Ranchalis, J. E., Pankey, S. C., Reed, M. J., and Gombotz, W. R., 1995, The enhancement in wound healing by transforming growth factor beta 1 (TGF-β 1) depends on the topical delivery system, J. Surg. Res. 58:321–329.

    Article  CAS  PubMed  Google Scholar 

  • Purchio, A. F., Cooper, J. A., Brunner, A. M., Lioubin, M. N., Gentry, L. E., Kovacine, K. S., Roth, R. A., and Marquardt, H., 1988, Identification of mannose 6-phosphate in two asparagine-linked sugar chains of recombinant transforming growth factor beta 1 precursor, J. Biol. Chem. 263:14211–14215.

    CAS  PubMed  Google Scholar 

  • Reiss, M., and Sartorelli, A. C., 1987, Regulation of growth and differentiation of human keratinocytes by type beta transforming growth factor and epidermal growth factor, Cancer Res. 47:6705–6709.

    CAS  PubMed  Google Scholar 

  • Reznikoff, C. A., Brankow, D. W., and Heidelberger, C., 1973, Establishment and characterization of a cloned line of C3H mouse embryo cells sensitive to postconfluence inhibition of division, Cancer Res. 33:3231–3238.

    CAS  PubMed  Google Scholar 

  • Roberts, A. B., Anzano, M. A., Lamb, L. C., Smith, J. M., and Sporn, M. B.. 1981, New class of transforming growth factors potentiated by epidermal growth factor: Isolation from nonneoplastic tissues, Proc. Natl. Acad. Sci. 78:5339–5343.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Roberts, A. B., Anzano, M. A., Wakefield, L. M., Roche, N. S., Stern, D. F., and Sporn, M. B., 1985, Type beta transforming growth factor: a bifunctional regulator of cellular growth, Proc. Natl. Acad. Sci. 82:119–123.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Roberts, A. B., and Sporn, M. B., 1990, Transforming growth factor-βs, in: Handbook of Experimental Pharmacology, Vol. 95, Springer-Verlag, Berlin, pp. 419–472.

    Google Scholar 

  • Roberts, A. B., Sporn, M. B., Assoianm, R. K., Smoth, J. M., Roche, N. S., Wakefield, L. M., Heine, U. I., Liotta, L. A., Falanga, V., Kehrl, J. H., and Fauci, A. S., 1986, Transforming growth factor type β Rapid induction of fibrosis and angiogenesis in vivo and stimulation of collagen formation in vitro, Proc. Natl. Acad. Sci. 83:4167–4171.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ryle, A. P., and Sanger, F., 1955, Bisulfide interchange reactions, Biochem. J. 60:535–540.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Schein, C. H., 1990, Solubility as a function of protein structure and solvent components. Biotechnology 8:308–317.

    Article  CAS  PubMed  Google Scholar 

  • Schultz, G., Chegini, N., Grant, M., Khaw, P., and MacKay, S., 1992, Effects of growth factors on corneal wound healing, Ada Ophthalmol., Suppl. 70, pp. 60–66.

    Google Scholar 

  • Seyedin, S. M., Segarini, P. R., and Rosen, D. M., 1987, Cartilage inducing factor-β 2 is a unique protein structurally and functionally related to transforming growth factor-beta, J. Biol. Chem. 262:1946–1949.

    CAS  PubMed  Google Scholar 

  • Seyedin, S. M., Thompson, A.Y., Bentz, H., Rosen, D. M., McPherson, J. M., Conti, A., Siegel, N. R., Galluppi, G. R., and Piez, K. A., 1986, Cartilage-inducing factor-A. Apparent identity to transforming growth factor-beta, J. Biol. Chem. 261:5693–5695.

    CAS  PubMed  Google Scholar 

  • Sharpies, K., Plowman, G. D., Rose, T. M., Twardzik, D. R., and Purchio, A. F, 1987, Cloning and sequence analysis of simian transforming growth factor-β cDNA, DM4 6:239–244.

    Google Scholar 

  • Smiddy, W. E., Glaser, B. M., and Green, W. R., 1989, Transforming growth factor beta. A biologic chorioretinal glue, Arch. Opthalmol. 107:577–580.

    Article  CAS  Google Scholar 

  • Smiddy, W. E., Glaser, B. M., Thommepson, J. T., Sjaarda, R. N., Flynn, H. W., Hanham, A., and Murphy, R. P., 1993, Transforming growth factor β 2 significantly enhances the ability to flatten the rim of subretinal fluid surrounding macular holes, Retina 13:296–301.

    Article  CAS  PubMed  Google Scholar 

  • Sporn, M. B., and Roberts, A. B., 1989, Transforming growth factor-beta. Multiple actions and potential clinical applications, JAMA 262:938–941.

    Article  CAS  PubMed  Google Scholar 

  • Sporn, M. B., Roberts. A. B., Wakefield, L. M., and Assoian, R. K., 1986, Transforming growth factor-β Biological function and chemical structure, Science 233:532–534.

    Article  CAS  PubMed  Google Scholar 

  • Sumner, D. R., Turner, T. M., Purchio, A. F., Gombotz, W. R., Urban, R. M., and Galante, J. O., Enhancement of bone ingrowth by transforming growth factor beta, J. Bone Joint Surg., in press.

    Google Scholar 

  • Tanaka, T., Taniguchi, Y., Gotoh, K., Satoh, R., Inazu, M., and Ozawa, H., 1993, Morphological study of recombinant human transforming growth factor β 1-induced intramembranous ossification in neonatal rat parietal bone, Bone 14:117–123.

    Article  CAS  PubMed  Google Scholar 

  • Toriumi, D. M., East, C. A., and Larrabee, W. F., 1991, Osteoinductive biomaterials for medical implantation, J. Long Term Effects Med. Implants 1:53077.

    Google Scholar 

  • Tucker, R. F., Branum, E. L., Shipley, G. D., Ryan, R. J., and Moses, H. L., 1984, Specific binding to cultured cells of 125I-labeled type beta transforming growth factor from human platelets, Proc. Natl. Acad. Sci. 81:6757–6761.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tucker, R. F., Shipley, G. D., Moses, H. L., and Holley, R. W., 1984, Growth inhibitor from BSC-1 cells closely related to platelet type beta transforming growth factor, Science 226:705–707.

    Article  CAS  PubMed  Google Scholar 

  • Twardzik, D. R., Mikovits, J. A., Ranchalis, J. E., Purchio, A. F., and Ellingsworth, L., 1990, Interferon activation of latent transforming growth factor-β by human monocytes, Ann. N. Y. Acad. Sci. 593:276–284.

    Article  CAS  PubMed  Google Scholar 

  • Wakefield, L. M., Smith, D. M., Flanders, K. C., and Sporn, M. B., 1988, Latent transforming growth factor-beta from human platelets. A high molecular weight complex containing precursor sequences, J. Biol. Chem. 263:7646–7654.

    CAS  PubMed  Google Scholar 

  • Wang, Y. J., and Hanson, M. A., 1988, Parenteral formulations of proteins and peptides: Stability and stabilizers, J. Parent. Sci. Tech. Suppl. 42:S3–S26.

    Google Scholar 

  • Wozney, J. M., Rosen, V., Celeste, A. J., Mitsock, L. M., Whitters, M. J., Kriz, R. W., Hewick, R. M., and Wang, E. A., 1988, Novel regulators of bone formation: Molecular clones and activities, Science 242:1528–1534.

    Article  CAS  PubMed  Google Scholar 

  • Zale, S. E., and Klibanov, A. M., 1986, Why does ribonuclease irreversibly inactivate at high temperatures?, Biochemistry 25:5432–5444.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Drug Delivery and Formulation, Immunex Corporation, Seattle, Washington, 98101, USA

    Wayne R. Gombotz

  2. Pharmaceutical Research Institute, Bristol-Myers Squibb, Seattle, Washington, 98101, USA

    Susan C. Pankey, Lisa S. Bouchard & Duke H. Phan

  3. Mercer Island, Washington, 98040, USA

    Alan P. MacKenzie

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  5. Alan P. MacKenzie
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  1. Megabios Corporation, Burlingame, California, USA

    Rodney Pearlman

  2. Scios Nova, Inc., Mountain View, California, USA

    Y. John Wang

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Gombotz, W.R., Pankey, S.C., Bouchard, L.S., Phan, D.H., MacKenzie, A.P. (2002). Stability, Characterization, Formulation, and Delivery System Development for Transforming Growth Factor-Beta1 . In: Pearlman, R., Wang, Y.J. (eds) Formulation, Characterization, and Stability of Protein Drugs: Case Histories. Pharmaceutical Biotechnology, vol 9. Springer, Boston, MA. https://doi.org/10.1007/0-306-47452-2_4

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