IP Library › Granted Patent US 12,280,101
Granted Patent B2
US 12,280,101 · App. 15/858,239 · Granted Apr 22, 2025

Compositions and methods for stabilization of active agents

Inventors: David L. Kaplan (Concord, MA); Fiorenzo G. Omenetto (Lexington, MA)
Assignee: Trustees of Tufts College
A61K39/20A61K9/0019A61K9/06A61K9/146A61K9/19A61K9/5026A61K9/5063A61K9/7007A61K39/0015A61K39/02A61K39/04A61K39/08A61K39/092A61K39/095A61K39/099A61K39/12A61K39/165A61K47/42A61K47/46B82Y5/00A61K38/00A61K2039/5252A61K2039/5254A61K2039/6031A61K2039/622A61K2039/64A61K2039/70C12N2760/18434C12N2760/18734C12N2770/36234Y02A50/30
View Patent ↗
Loading inventors, assignments & file history…
Monitor This Case
Get email alerts when status or documents change.
Order Certified Copies
Most orders are placed with the USPTO same day — all within 24 business hours.
Order via The Patent Place →
Pre-filled with this patent's details
Quick Facts
Patent No.
US 12,280,101
App. No.
15/858,239
Granted
Apr 22, 2025
Kind
B2
Abstract

Provided herein are methods and compositions for stabilization of active agents. The active agents are distributed, mixed or embedded in a silk fibroin matrix, thereby retaining the bioactivity of the active agents upon storage and/or transportation. In some embodiments, the storage-stable vaccine-silk compositions are also provided herein.

Claims (26)

1. A storage-stable composition comprising a silk fibroin film, particle, or microneedle and an active agent distributed therein, wherein the active agent is a vaccine, wherein administering the composition to a subject initiates sustained release of the active agent over a period of at least 1 hour; and the active agent retains at least about 30% of its original bioactivity when the composition is (a) subjected to at least one freeze-thaw cycle, or (b) maintained for at least about 24 hours at a temperature above 0° C., or (c) both (a) and (b).

2. The storage-stable composition of claim 1 , wherein the active agent retains at least about 30% of its original bioactivity when the composition is (a) subjected to at least one freeze-thaw cycle, and (b) maintained for at least about 24 hours at a temperature above 0° C.

3. The storage-stable composition of claim 1 , wherein the active agent retains at least about 60% of its original bioactivity when the composition is (a) subjected to at least one freeze-thaw cycle, or (b) maintained for at least about 24 hours at a temperature above 0° C., or (c) both (a) and (b).

4. The storage-stable composition of claim 1 , wherein the active agent retains at least about 60% of its original bioactivity when the composition is (a) subjected to at least one freeze-thaw cycle, and (b) maintained for at least about 24 hours at a temperature above 0° C.

5. The storage-stable composition of claim 1 , the composition further comprising a stabilizing agent selected from the group consisting of a saccharide, a sugar alcohol, an ion, a surfactant, and combinations thereof.

6. The storage-stable composition of claim 5 , wherein the stabilizing agent is a saccharide.

7. The storage-stable composition of claim 6 , wherein the saccharide is sucrose.

8. The storage-stable composition of claim 5 , wherein the stabilizing agent is a sugar alcohol.

9. The storage-stable composition of claim 8 , wherein the sugar alcohol is sorbitol or mannitol.

10. The storage-stable composition of claim 1 , wherein the vaccine comprises an antigenic molecule that when introduced into the subject's body produces immunity to a specific disease by causing the activation of the immune system, antibody formation, and/or creating of a T-cell and/or B-cell response.

11. The storage-stable composition of claim 1 , wherein the vaccine is a live, attenuated virus or an inactivated virus.

12. The storage-stable composition of claim 11 , wherein the live, attenuated virus or inactivated virus is chosen from a measles virus, a mumps virus, a rubella virus, a varicella virus, a flavivirus, a yellow fever virus, an influenza virus, a rotavirus, a reovirus, a hepatitis virus, a rabies virus, and a poliovirus.

13. The storage-stable composition of claim 11 , wherein the live, attenuated virus or the inactivated virus shows an increased half-life of at least about 1.5-fold at a temperature of at least about 20° C., compared to the live, attenuated virus or the inactivated virus without the silk fibroin film, particle, or microneedle.

14. The storage-stable composition of claim 1 , wherein the original bioactivity is original immunogenicity.

15. The storage-stable composition of claim 14 , wherein the vaccine retains at least 30% of its original immunogenicity after the composition is maintained at 4° C. for 4 weeks.

16. The storage-stable composition of claim 1 , wherein the original bioactivity is original infectivity.

17. The storage-stable composition of claim 16 , wherein the vaccine retains at least 30% of its original infectivity for at least about 24 hours at a temperature of at least about room temperature or higher.

18. The storage-stable composition of claim 1 , wherein the silk fibroin film, particle, or microneedle comprises a silk fibroin concentration of about 0.5% w/v to about 20% w/v.

19. The storage-stable composition of claim 1 , wherein the silk fibroin film, particle, or microneedle is in an air-dried, nitrogen-dried, or lyophilized form.

20. The storage-stable composition of claim 1 , wherein the composition is formulated for transdermal delivery.

21. The storage-stable composition of claim 1 , wherein the composition is implantable.

22. The storage-stable composition of claim 1 , wherein the composition has a residual moisture that is adapted to provide storability such that the active agent retains at least about 30% of its original bioactivity when the composition is (a) subjected to at least one freeze-thaw cycle, or (b) maintained for at least about 24 hours at a temperature above 0° C., or (c) both (a) and (b).

23. The storage-stable composition of claim 1 , which is a microneedle.

24. The storage-stable composition of claim 23 , wherein the microneedle is configured to puncture the skin of a subject and release the vaccine subcutaneously.

25. The storage-stable composition of claim 24 , wherein the microneedle is configured to release the vaccine by dissolving.

26. A storage-stable composition comprising a silk fibroin film, particle, or microneedle and an active agent distributed therein, the active agent is a vaccine having a bioactivity that is reduced upon being subjected to either at least one freeze-thaw cycle or maintenance for at least 24 hours at a temperature of above 0° C. in the absence of the silk fibroin film, particle, or microneedle, the composition having a residual moisture that is adapted to provide storage stability such that the active agent has at least about 30% greater bioactivity relative to the active agent in the absence of the silk fibroin film, particle, or microneedle when the composition or the at least one active agent in the absence of the silk fibroin film, particle, or microneedle is (a) subjected to at least one freeze-thaw cycle, or (b) maintained for at least about 24 hours at a temperature of above 0° C., or (c) both (a) and (b), and wherein administering the composition to a subject initiates sustained release of the active agent over a period of at least 1 hour.

Assignments (2)
CONFIRMATORY LICENSE Recorded Mar 21, 2018
From: TUFTS UNIVERSITY BOSTON
To: NATIONAL INSTITUTES OF HEALTH (NIH), U.S. DEPT. OF HEALTH AND HUMAN SERVICES (DHHS), U.S. GOVERNMENT
Reel/Frame 045665/0376 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jan 4, 2018
From: KAPLAN, DAVID L.; OMENETTO, FIORENZO G.
To: TRUSTEES OF TUFTS COLLEGE
Reel/Frame 044534/0846 →
Continuity (4)
Continuation 15492363 · Apr 20, 2017
Division 14112769
Provisional Application 61477737 · Apr 21, 2011
Related Publication 20180360947A1 · Dec 20, 2018
References Cited (153)
US 3832253A · Palma · 1974 [cited by applicant]
US 3854480A · Zaffaroni · 1974 [cited by applicant]
US 4452775A · Kent · 1984 [cited by applicant]
US 4667014A · Nestor, Jr. · 1987 [cited by applicant]
US 4675189A · Kent · 1987 [cited by applicant]
US 4748034A · de Rham · 1988 [cited by applicant]
US 5075109A · Tice · 1991 [cited by applicant]
US 5133974A · Paradissis · 1992 [cited by applicant]
US 5239660A · Ooi · 1993 [cited by applicant]
US 5245012A · Lombari · 1993 [cited by applicant]
US 5346481A · Bunin · 1994 [cited by applicant]
US 5407686A · Patel · 1995 [cited by applicant]
US 5736152A · Dunn · 1998 [cited by applicant]
US 5797898A · Santini, Jr. · 1998 [cited by applicant]
US 5900238A · Gombotz · 1999 [cited by applicant]
US 6669683B2 · Santini, Jr. · 2003 [cited by applicant]
US 7052488B2 · Uhland · 2006 [cited by applicant]
US 7060260B2 · Fahnestock · 2006 [cited by applicant]
US 7582080B2 · Santini, Jr. · 2009 [cited by applicant]
US 7635755B2 · Kaplan · 2009 [cited by applicant]
US 7842780B2 · Kaplan · 2010 [cited by applicant]
US 8206774B2 · Kaplan et al. · 2012 [cited by applicant]
US 20040096455A1 · Maa · 2004 [cited by applicant]
US 20040133160A1 · Dalton · 2004 [cited by applicant]
US 20050112135A1 · Cormier · 2005 [cited by applicant]
US 20050123565A1 · Subramony · 2005 [cited by applicant]
US 20050255121A1 · Campbell · 2005 [cited by applicant]
US 20090043280A1 · Dalton · 2009 [cited by applicant]
US 20090142836A1 · Wang · 2009 [cited by applicant]
US 20090143724A1 · Cormier · 2009 [cited by applicant]
US 20090155330A1 · Ghartey-Tagoe · 2009 [cited by examiner]
US 20090182306A1 · Lee · 2009 [cited by examiner]
US 20090202614A1 · Kaplan · 2009 [cited by examiner]
US 20100028451A1 · Kaplan · 2010 [cited by applicant]
US 20100178304A1 · Wang · 2010 [cited by applicant]
US 20100279112A1 · Kaplan · 2010 [cited by applicant]
US 20110171239A1 · Kaplan · 2011 [cited by applicant]
US 20120052124A1 · Kaplan · 2012 [cited by applicant]
US 20140287043A1 · Kaplan · 2014 [cited by applicant]
EP 0290197 · 1988 [cited by applicant]
EP 0404097 · 1990 [cited by applicant]
EP 1725258 · 2006 [cited by applicant]
JP S628054 · 1987 [cited by applicant]
JP S6393727 · 1988 [cited by applicant]
JP S646220 · 1989 [cited by applicant]
JP H02311500 · 1990 [cited by applicant]
JP H11151438 · 1999 [cited by applicant]
JP 2000507963 · 2000 [cited by applicant]
JP 2005097229 · 2005 [cited by applicant]
RU 21271 · 2002 [cited by applicant]
WO 199311161 · 1993 [cited by applicant]
WO 1997008315 · 1997 [cited by applicant]
WO 199828000 · 1998 [cited by applicant]
WO 2004062697 · 2004 [cited by applicant]
WO 2005016239 · 2005 [cited by applicant]
WO 2005085327 · 2005 [cited by applicant]
WO 2006062685 · 2006 [cited by applicant]
WO WO2006076711 · 2006 [cited by applicant]
WO WO2008118133 · 2008 [cited by applicant]
WO 2012054582 · 2012 [cited by applicant]
You et al. “Rapidly dissolving fibroin microneedles for transdermal drug delivery,” Materials Science and Engineering C 31:1632-1636, 2011 (available online Jun. 28, 2011). [cited by examiner]
You et al. “Rapidly dissolving fibroin microneedles for transdermal drug delivery,” Proceedings of the 2010 IEEE, pp. 144-147, 2010. [cited by examiner]
Mathur et al. “Silk fibroin-derived nanoparticles for biomedical applications,” Nanomedicine, 5(5):807-820, 2010. [cited by examiner]
Wikipedia “Conjugate vaccine,” last edited Dec. 18, 2019; https://en.wikipedia.org/wiki/Conjugate_vaccine. [cited by examiner]
ip.com translation of DE-20-2011-100790, published Oct. 26, 2011, printed 2020 (Year: 2020). [cited by examiner]
Wang et al. “In vivo degradation of three-dimensinal silk fibroin scaffolds,” Biomaterials 29:3415-3428, 2008 (Year: 2008). [cited by examiner]
Ohtake, S. et al., Arginine as a Synergistic Virucidal Agent, Molecules, 15(3): 1408-1424 (2010). [cited by applicant]
Ohtake, S. et al., Heat-stable measles vaccine produced by spray drying, Vaccine, 28(5):1275-84 (2010). [cited by applicant]
Ohtsuka, E. et al., An alternative approach to deoxyoligonucleotides as hybridization probes by insertion of deoxyinosine at ambiguous codon positions, J. Biol. Chem., 260(5): 2605-2608 (1985). [cited by applicant]
Peetermans et al., Stability of freeze-dried rubella virus vaccine (Cendehill strain) at various temperatures, 1 J. Biological Standardization 179 (1973). [cited by applicant]
Perry, H. et al., Nano- and Micropatterning of Optically Transparent, Mechanically Robust, Biocompatible Silk Fibroin Films, Advanced Materials, 20:3070-3072 (2008). [cited by applicant]
Pluckthun, The Pharmacology of Monoclonal Antibodies, vol. 113, Rosenburg and Moore eds., Springer-Verlag, New York, pp. 269-315 (1994). [cited by applicant]
Pritchard, E. et al., Silk fibroin encapsulated powder reservoirs for sustained release of adenosine, Journal of Controlled Release, 144(2):159-167 (2010). [cited by applicant]
Pritchard, E.M. et al., Physical and chemical aspects of stabilization of compounds in silk, Biopolymers, 97(6):479-498 (2012). [cited by applicant]
Rapp, F. et al., Protection of measles virus by sulfate ions against thermal inactivation, J. Bact., 90(1): 132-135 (1965). [cited by applicant]
Retraction: Applied Biological Sciences, Engineering, PNAS, 113(26): E3810, 6 pages (2016). [cited by applicant]
Rexroad, J. et al., Effect of pH and ionic strength on the physical stability of adenovirus type 5, Journal of Pharmaceutical Sciences, 95(2): 237-247 (2006). [cited by applicant]
Roberts, C.J., Non-Native Protein Aggregation Kinetics. Biotechnology and Bioengineering. 98 (5): 927-938 (2007). [cited by applicant]
Rossolini, G.M. et al., Use of Deoxyinosine-containing primers vs degenerate primers for polymerase chain reaction pased on ambiguous sequence information, Molecular and Cellular Probes, 8(2):91-98 (1994). [cited by applicant]
Russell, B. et al., The particle size of rubella virus, Journal of General Virology, 1(3): 305-310 (1967). [cited by applicant]
Santin et al. In vitro Evaluation of the Inflammatory Potential of the Silk Fibroin, J. Biomed. Mater. Res. 46:382-389 (1999). [cited by applicant]
Schalk, J.A. et al., Potency estimation of measles, mumps and rubella trivalent vaccines with quantitative PCR Infectivity assay, Biologicals, 33(2): 71-79 (2005). [cited by applicant]
Sofia, et al., Functionalized silk-based biomaterials for bone formation, Journal of Biomedical Materials Research, 54 (1):139-148 (2001). [cited by applicant]
Tsioris, K. et al., Fabrication of silk microneedles for controlled-release drug delivery, Advanced Functional Materials (2011). [cited by applicant]
Vepari, C. et al., Silk as a Biomaterial, Prog. Polym. Sci., 32(8-9): 991-1007 (2007). [cited by applicant]
Wang, X. et al., Sonication-Induced Gelation of Silk-Fibroin for Cell Encapsulation, Biomaterials, 29(8): 1054-1064 (2008). [cited by applicant]
Wang, X. et al., Silk nanospheres and microspheres from silk/pva blend films for drug delivery, Biomaterials, 31(6): 1025-1035 (2010). [cited by applicant]
Wang, X., Controlled release from multilayer silk biomaterial coatings to modulate vascular cell responses, Biomaterials, 29(7): 894-903 (2008). [cited by applicant]
Waterman, K. and Adami, R.C., Accelerated aging: Prediction of chemical stability of pharmaceuticals, International Journal of Pharmaceutics, 293(1-2): 101-125 (2005). [cited by applicant]
Wenk, et al., Silk Fibroin Spheres as a Platform for Controlled Drug Delivery, Journal of Controlled Release, 132 (1):26-34 (2008). [cited by applicant]
WHO (2006). Temperature sensitivity of vaccines. WHO publications. [Online]. The reference can be accessed at whqlibdoc.who.int/hq/2006/WHO_IVB_06.10_eng.pdf. [cited by applicant]
WHO, UNAIDA, World Bank, UNESCO, UNFPA (2000). Health: a key to prosperity. In: Success Stories in Developing Countries. World Health Organization, Geneva. [cited by applicant]
WHO. (1982). Report of Expert Committee on Biological Standardization. Thirty-second report. Requirement for measles vaccine (live). Addendum 1981, Geneva, World Health Organization. (Technical Report Series No. 673, An… [cited by applicant]
WHO. (1994). Report of Expert Committee on Biological Standardization. Requirements for measles, mumps and rubella vaccines and combined vaccines (live). Geneva, World Health Organization. (Technical Report Series, No. … [cited by applicant]
WHO. (2011). Measles. Media centre fact sheet No. 286. Oct. 2011. [online]. The reference can be accessed at who.int/mediacentre/factsheets/fs286/en/. [cited by applicant]
Wightman, G. et al., An investigation into the behaviors of air rifle pellets in ballistic gel and their interaction with bone, Forensic Science International, 200 (1-3): 41-49 (2007). [cited by applicant]
Wild, T.F. et al., Measles vims: both the haemagglutinin and fusion glycoproteins are required for fusion, Journal of General Virology, 72 (Pt 2): 439-442 (1991). [cited by applicant]
Woelk, C.H. et al., Increased positive selection pressure in persistent (SSPE) versus acute measles vims infections, Journal of General Virology, 83(Pt 6): 1419-1430 (2002). [cited by applicant]
Wolfson, L.J. et al., Estimating the costs of achieving the WHO-UNICEF Global Immunization Vision and Strategy, 2006-2015, Bulletin of the World Health Organization, 86(1): 27-39 (2008). [cited by applicant]
Worrall, E.E. et al., Xerovac: an ultra-rapid method for the dehydration and preservation of live attenuated Rinderpest and Peste des Petits ruminants vaccines, Vaccine, 19(7-8): 834-839 (2001). [cited by applicant]
Written Opinion for PCT/US12/34643, 5 pages (Sep. 6, 2012). [cited by applicant]
Yildirim, S. et al., Development of silk fibroin-based beads for immobilized cell fermentations, Journal of Microencapsulation, 27(1): 1-9 (2010). [cited by applicant]
Zapata, G. et al., Engineering linear F(ab')2 fragments for efficient production in [cited by applicant]
Zweig, S.E., Advances in vaccine stability monitoring technology, Vaccine, 24(33-34): 5977-5985 (2006). [cited by applicant]
Adu, F.D., et al., Live viral vaccine potency: an index for assessing the cold chain system, Public Health, 110(6): 325-330 (1996). [cited by applicant]
Altman, G. H. et al., Silk-based biomaterials, Biomaterials, 24:401-416 (2003). [cited by applicant]
Arora, A., et al., Micro-scale devices for transdermal drug delivery, International Journal of Pharmaceutics. 364: 227-236 (2008). [cited by applicant]
Arya, S.C., Stabilization of vaccines: to be or not to be, Vaccine, 19(4-5):595-597 (2001). [cited by applicant]
Ausar, S.F., et al., Conformational stability and disassembly of Norwalk virus like particles: effect of pH and temperature, Journal of Biological Chemistry, 281(28): 19478-19488. (2006). [cited by applicant]
Batzer, M.A. et al., Enhanced evolutionary PCR using oligonucleotides with insosine at the 3′-terminus, Nucleic Acids Research, 19(18): 5081 (1991). [cited by applicant]
Beauchamp, J. and Mansoor, O., Temperature and the storage of vaccines, New Zealand Medical Journal. 105 (931): 135 (1992). [cited by applicant]
Bishai, D.M., Vaccine storage practices in pediatric offices, Pediatrics, 89(2): 193-196 (1992). [cited by applicant]
Brandau, D.T. et al., Thermal Stability of Vaccines, Journal of Pharmaceutical Sciences, 92(2): 218-231 (2003). [cited by applicant]
Center for Disease Control (CDC) Monthly Immunization Table, 45 MMWR 24 (1996). [cited by applicant]
Chen, D. and Kristensen, D., Opportunities and challenges of developing thermostable vaccines, Expert Review of Vaccines, 8(5): 547-558 (2009). [cited by applicant]
Cheriyan, E., Monitoring the vaccine cold chain, Archives of disease in childhood, 69(5): 600-601 (1993). [cited by applicant]
Cheyne, J., Vaccine delivery management, Rev. Infect. Dis., 11(Suppl. 3): S617-S622 (1989). [cited by applicant]
Chinese Patent Office Search Report for 2012800305827, mailing date of Feb. 17, 2015, 2 pages. [cited by applicant]
Chinese Patent Office Search Report for 2015105598406, mailing date of Jul. 19, 2017, 11 pages. [cited by applicant]
Chothia, C. et al., Canonical structure for the hypervariable regions of immunoglobulins, Journal of Molecular Biology, 196(4):901-917 (1987). [cited by applicant]
Colinet G. et al., A study of the stability of a bivalent measles-mumps vaccine, Journal of Biological Standardization, 10(4): 341-346 (1982). [cited by applicant]
Creighton, T.E., Protein folding, Biochemical Journal, 270(1): 1-16 (1990). [cited by applicant]
Dorsett, P.H. et al., Structure and function of the rubella virus proteins, Reviews of Infectious Diseases, 7(1): S150-S156 (1985). [cited by applicant]
European Search Report for EP 12774253.4, 9 pages (Nov. 24, 2014). [cited by applicant]
Evans, M. and Pope, M., Vaccine handling and storage in general practice, Health Trends, 27: 124-126 (1995). [cited by applicant]
Galazka et al., Thermostability of vaccines, in Global Programme for Vaccines & Immunization (World Health Organization, Geneva, 1998). [cited by applicant]
Hall, W.W. and Martin, S.J., Purification and Characterization of Measles Virus, Journal of General Virology, 19(2): 175-188 (1973). [cited by applicant]
Health Protection Agency, Foreign travel-associated illness, England, Wales, and Northern Ireland: 2007 report. London: Health Protection Agency (2007). [cited by applicant]
Hoffman, et al., Silk Fibroin as an Organic Polymer for Controlled Drug Delivery, Journal of Controlled Release, 11 (1-2):219-227 (2006). [cited by applicant]
Holliger, P. et al, “Diabodies”: small bivalent and bispecific antibody fragments, Proc. Natl. Acad. Sd. USA, 90: 6444-6448 (1993). [cited by applicant]
Horan, RL et al., In vitro degradation of silk fibroin, Biomaterials, 26(17): 3385-93 (2005). [cited by applicant]
Hu, X. et al., Effect of water on the thermal properties of silk fibroin, Thermochimica Acta, 461: 137-144 (2007). [cited by applicant]
Hubschen, J.M. et al., A multiplex TaqMan PCR assay for the detection of measles and rubella virus, J. Virol. Methods, 149(2): 246-250 (2008). [cited by applicant]
International Search Report for PCT/US12/34643, 4 pages (Sep. 6, 2012). [cited by applicant]
Jin, H.J. and Kaplan, D.L., Mechanism of silk processing in insects and spiders, Nature 424(6952):1057-1061 (2003). [cited by applicant]
Kikuchi, J. et al., Spectroscopic investigation of tertiary fold of staphylococcal protein A to expore its engineering application, Biomaterials 20(7): 647-654 (1999). [cited by applicant]
Kingston, R.L. et al., Structure of the nucleocapsid-binding domain from the mumps virus polymerase; An example of protein folding induced by crystallization, Journal of Molecular Biology, 379(4): 719-731 (2008). [cited by applicant]
Kissman, J. et al., Stabilization of measles virus for vaccine formulation, Human Vaccines. 4(5): 350-359(2008). [cited by applicant]
Koppel, D.E., Analysis of macromolecular polydispersity in intensity correlation spectroscopy: The method of cumulants, Journal of Chemical Physics, 57(11): 4814-4820 (1972). [cited by applicant]
Kubar, A. et al., Rapid and quantitative detection of mumps virus RNA by one-step real-time RT-PCR, Diagnostic Microbiology and Infectious Disease, 49(2): 83-88 (2004). [cited by applicant]
Kumakura, M., Effect of heat treatment on enzyme entrapped into polymer gels, Journal of Molecular Catalysis B: Enzymatic, L1-L6 (1995). [cited by applicant]
Lee, S. et al., Chemical instability of protein pharmaceuticals: mechanisms of oxidation and strategies of stabilization, Biotechnology and Bioengineering, 48(5): 490-500 (1994). [cited by applicant]
Liddle, J.L.M. and Harris, M.F., How general practitioners store vaccines. A survey in south-western Sydney, The Medical Journal of Australia, 162: 366-368 (1995). [cited by applicant]
Lu, S. et al., Stabilization of Enzymes in Silk Films, Biomacromolecules, 10(5): 1032-1042 (2009). [cited by applicant]
Lucas et al., “The silk fibroins.” Advances in protein chemistry. vol. 13. Academic Press, 1958. 107-242. [cited by applicant]
Malvoisin, E. and Wild T.F., Measles virus glycoproteins: studies on the structure and interaction of the haemagglutinin and fusion proteins, Journal of General Virology, 74(Pt 11): 2365-2372 (1993). [cited by applicant]
Manning, M.D. and Borchardt, P.K., Stability of pharmaceutical proteins, Pharmaceutical Research, 6(11): 903-918 (1989). [cited by applicant]
McAleer, W.J. et al., Stability on storage at various temperatures of live measles, mumps and rubella virus vaccines in new stabilizer, 8(4): 281-287 (1980). [cited by applicant]
Middaugh, C.R., Formulation and delivery of biopharmaceuticals, Journal of Pharmaceutical Sciences, 85: 1259-1260 (1996). [cited by applicant]
Mirchamsy et al., Stabilizing effect of magnesium chloride and sucrose on Sabin live polio vaccine, 41 Devel. Biol. Standardization 255 (1978). [cited by applicant]
Moss, W.J. and Gliffin, D.E., Global measles elimination, Nature Review Microbiology, 4(12): 900-908 (2006). [cited by applicant]
Murphy, A.R. et al., Modification of Silk Fibroin Using Diazonium Coupling Chemistry and the Effects on hMSC Proliferation and Differentiation, Biomaterials, 29(19):2829-2838 (2008). [cited by applicant]
Nakhasi, H.L. et al., Specific binding of host cell proteins to the 3′-terminal stem-loop structure of rubella virus negative-strand RNA, Journal of Virology, 65(11): 5961-5967 (1991). [cited by applicant]
Cited By (1)
US 12,636,250