IP Library Granted Patent US 12,697,374
Granted Patent B2
US 12,697,374 · App. 18/581,040 · Granted Aug 4, 2026

Use of clostridium histolyticum protease mixture in promoting wound healing

Inventors: Ira Herman (Boston, MA); Vincent Ronfard (Keller, TX); Lei Shi (Mansfield, TX)
A61K38/4886A61K9/0014A61K9/06A61K9/7007A61K35/74A61K38/48A61K45/06C12Y304/24003
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Quick Facts
Patent No.
US 12,697,374
App. No.
18/581,040
Filed
Feb 19, 2024
Granted
Aug 4, 2026
Kind
B2
Art Unit
1638
USPC
424/94.67
Abstract

Provided are methods for repairing a wound or inducing the proliferative phase of a wound comprising administering a composition comprising a protease mixture comprising collagenases and a neutral protease to the wound in an amount effective for repair of wound tissue or for inducing the proliferative phase in the wound.

Claims (23)

1 . A method for treating a wound, the method comprising administering a composition comprising a protease mixture comprising collagenases and a neutral protease to the wound in an amount effective for treating the wound,

wherein the protease mixture is obtained from fermenting Clostridium histolyticum and comprises collagenase ColG, collagenase ColH, and non-specific neutral protease,

wherein the wound is not in need of debridement, and

wherein the protease mixture is administered to the wound prior to granulation tissue formation in the wound and promotes granulation tissue formation in the wound.

2 . The method of claim 1 , wherein the wound is substantially devoid of necrotic tissue.

3 . The method of claim 1 , wherein the wound is entirely devoid of necrotic tissue.

4 . The method of claim 1 , wherein the wound was debrided prior to administration of the composition.

5 . The method of claim 4 , wherein the wound was debrided with an enzymatic debriding agent.

6 . The method of claim 5 , wherein the enzymatic debriding agent comprises a protease mixture obtained from fermenting Clostridium histolyticum and comprises collagenase ColG, collagenase ColH, and non-specific neutral protease.

7 . The method of claim 1 , wherein administration of the composition to the wound induces fibroblast proliferation, induces angiogenesis, epithelialization, or a combination thereof to promote repair of the wound.

8 . The method of claim 1 , wherein the composition is comprised in a wound dressing.

9 . The method of claim 8 , wherein the wound dressing is a patch, wrap, or bandage.

10 . The method of claim 1 , wherein the composition is a spray, liquid, salve, dissolvable gel-forming film, cream, powder, film, or semi-solid.

11 . The method of claim 1 , wherein the composition is sterile.

12 . The method of claim 1 , wherein the composition is administered topically.

13 . The method of claim 1 , wherein the composition consists of collagenase ColG, collagenase ColH, non-specific neutral protease, and petrolatum.

14 . The method of claim 1 , wherein the composition does not include petrolatum.

15 . The method of claim 1 , wherein the composition further comprises an antimicrobial agent selected from an antibiotic or an antiseptic.

16 . The method of claim 1 , wherein the wound is a burn.

17 . The method of claim 1 , wherein the wound is a chronic wound or a non-healing wound.

18 . The method of claim 1 , wherein the wound is a diabetic foot ulcer, venous leg ulcer, arterial leg ulcer, decubitus ulcer, stasis ulcer, dermal ulcer, pressure ulcer or a peptic ulcer.

19 . The method of claim 1 , wherein the wound is a surgical, hypertrophic, cosmetic, or keloid scar.

20 . The method of claim 1 , wherein the wound is unhealed and in need of repair.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Oct 1, 2024
From: HERMAN, IRA; RONFARD, VINCENT; SHI, LEI
To: SMITH & NEPHEW, INC.
Reel/Frame 068752/0773 →
Continuity (3)
Continuation 15534547 · Dec 10, 2015
Provisional Application 62091313 · Dec 12, 2014
Related Publication 20240261377A1 · Aug 8, 2024
References Cited (30)
US 3705083A · Chiulli et al. · 1972 [cited by applicant]
US 3821364A · Chiulli et al. · 1974 [cited by applicant]
US 5718897A · Herman · 1998 [cited by applicant]
US 5851522A · Herman · 1998 [cited by applicant]
US 6548556B2 · Hobson et al. · 2003 [cited by applicant]
US 7785584B2 · Jones et al. · 2010 [cited by applicant]
US 8357655B2 · Herman · 2013 [cited by applicant]
US 8663617B2 · Herman · 2014 [cited by applicant]
US 9694100B2 · Shi et al. · 2017 [cited by applicant]
US 10058596B2 · Hanson · 2018 [cited by applicant]
US 20070128685A1 · Faudoa et al. · 2007 [cited by applicant]
US 20090010869A9 · Trumbore · 2009 [cited by examiner]
US 20130287759A1 · Munoz · 2013 [cited by examiner]
US 20160008293A1 · Shi et al. · 2016 [cited by applicant]
Ramundo et al. “Collagenase for Enzymatic Debridement” JWOCN Nov./Dec. 2009 (Year: 2009). [cited by examiner]
Das et al. “Novel mechanisms of Collagenase Santyl Ointment (CSO) in wound and resolutions of wound inflammation” Scientific Report (Year: 2017). [cited by examiner]
Shi et al. “Collagenase Santyl Ointment, A Selective Agent for Wound Debridement” JWOCN Nov./Dec. 2009 (Year: 2009). [cited by examiner]
Huang et al. “Ulceration and Delayed Healing Following Pressure Loading in Hyperglycemic Rats with an Immature Dermal Collagen Fiber Network” Wounds, 2010, 22(9); 237-244. (Year: 2010). [cited by examiner]
Merriam Webster Definition of the word “wound” (Year: 2025). [cited by examiner]
Saggini et al. “Extracorporeal shock wave therapy: an emerging treatment modality for retracting scars on the hands” Ultrasound in Med & Biol., vol. 42, No. 1, pp. 185-195, 2016. (Year: 2016). [cited by examiner]
Merriam Webster Definition of Wound (Year: 2025). [cited by examiner]
ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). Identifier NCT00651820, Effect of Collagenase on Healing and Scarring: Apr. 3, 2008 [Accessed on Aug. 7, 2018]: [16 pages] Available from:… [cited by applicant]
Collagenase SANTYL Ointment [prescription information], Healthpoint, Ltd., Fort Worth, Texas; 2013. [cited by applicant]
Collagenase Santyl Ointment Brochure by Healthpoint (Year: 2013). [cited by applicant]
Herman, I., “Stimulation of Human Keratinocyte Migration and Proliferation in Vitro: Insights into the Cellular Responses to Injury and Wound Healing,” Wounds: A Compendium of Clinical Research and Practice, 8(2), pp. 3… [cited by applicant]
International Search Report and Written Opinion Issued in Corresponding International Patent Application No. PCT/US2015/065024, mailed Apr. 3, 2016. [cited by applicant]
Postlehwaite, et al., “Chemotactic Attraction of Human Fibroblasts to Type I, II, and III Collagens and Collagen-Derived Peptides,” [cited by applicant]
Radice, et al. “Clostridial Collagenase Releases Bioactive Fragments from Extracellular Matrix Models”, [cited by applicant]
Swezey et al. “Wound Source” Article, https://www.woundsource.com (Year: 2013). [cited by applicant]
Tallis, et al., “Clinical and Economic Assessment of Diabetic Foot Ulcer Debridement with Collagenase: Results of a Randomized Controlled Study,” Clinical Therapeutics, 35(11), pp. 1805-1820. (2013). [cited by applicant]