IP Library Granted Patent US 11,872,267
Granted Patent B2
US 11,872,267 · App. 17/070,747 · Granted Jan 16, 2024

Treatment of uterine fibroids using purified collagenase

Inventors: James H. Segars (Baltimore, MD); Phyllis Carolyn Leppert (Salt Lake City, UT); Thomas L. Wegman (N. Merrick, NY); Jean-Marie Soma (Lynbrook, NY)
Assignees: The Johns Hopkins University; Duke University; BioSpecifics Technologies LLC
A61K38/4886A61K9/0019A61K9/0021A61K9/0034A61P15/00A61B5/4824C12Y304/24003
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Quick Facts
Patent No.
US 11,872,267
App. No.
17/070,747
Granted
Jan 16, 2024
Kind
B2
Abstract

Disclosed herein are compositions and methods for treating uterine fibroids in vivo, and methods of reducing symptoms associated with uterine fibroids, including pain, bleeding and infertility. The disclosed compositions comprise collagenase in an amount effective to cause shrinkage and/or reduce stiffness of uterine fibroids.

Claims (14)

1. A method for reducing the size of a uterine fibroid in a patient, the method comprising:

administering into the uterine fibroid a composition comprising Clostridium histolyticum collagenase I and collagenase II in a 1:1 mass ratio to thereby reduce the size of the uterine fibroid, wherein there is an at least two fold increase in LC3B expression within the uterine fibroid as measured at 60 days following the administration.

2. The method of claim 1 , wherein said composition is delivered through a delivery channel into said fibroid, wherein the delivery channel is in a needle, syringe, cannula, catheter or jet injector.

3. The method of claim 1 , wherein about 0.005 mg to about 10 mg collagenase is administered per cm 3 of tissue to be treated.

4. The method of claim 1 , wherein about 0.05 mg to about 1 mg collagenase is administered per cm 3 of tissue to be treated.

5. The method of claim 1 , wherein about 0.25 mg to about 1 mg collagenase is administered per cm 3 of tissue to be treated.

6. The method of claim 1 , wherein the method results in an at least three fold reduction in expression of proliferating cell nuclear antigen (PCNA) as measured at 60 days following the administration.

7. A method for reducing pain associated with a uterine fibroid in a patient, the method comprising:

administering into the uterine fibroid in the patient a composition comprising Clostridium histolyticum collagenase I and collagenase II in a 1:1 mass ratio to thereby reduce the pain associated with the uterine fibroid, wherein the patient has a reduction of at least 1 point on the McGill Pain Scale as measured at 60 days following the administration.

8. The method of claim 7 , wherein said composition is delivered through a delivery channel into said fibroid, wherein the delivery channel is in a needle, syringe, cannula, catheter or jet injector.

9. The method of claim 7 , wherein about 0.005 mg to about 10 mg collagenase is administered per cm 3 of tissue to be treated.

10. The method of claim 7 , wherein about 0.05 mg to about 1 mg collagenase is administered per cm 3 of tissue to be treated.

11. The method of claim 7 , wherein about 0.25 mg to about 1 mg collagenase is administered per cm 3 of tissue to be treated.

12. The method of claim 7 , wherein at 60 days following the administering the patient has a reduction of about 15 points on the McGill Pain Scale.

Assignments (16)
SECURITY INTEREST Recorded Jul 22, 2024
From: ENDO BIOLOGICS LIMITED; ENDO OPERATIONS LIMITED
To: COMPUTERSHARE TRUST COMPANY, NATIONAL ASSOCIATION
Reel/Frame 068469/0001 →
SECURITY INTEREST Recorded Jul 19, 2024
From: ENDO BIOLOGICS LIMITED; ENDO OPERATIONS LIMITED
To: GOLDMAN SACHS BANK USA
Reel/Frame 068461/0692 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Apr 27, 2024
From: ENDO USA, INC.
To: ENDO BIOLOGICS LIMITED
Reel/Frame 067245/0693 →
RELEASE OF SECURITY INTEREST Recorded Apr 26, 2024
From: WILMINGTON TRUST, NATIONAL ASSOCIATION
To: ACTIENT PHARMACEUTICALS LLC; ASTORA WOMEN’S HEALTH HOLDINGS, LLC; ASTORA WOMEN’S HEALTH LLC; AUXILIUM PHARMACEUTICALS, LLC; AUXILIUM US HOLDINGS, LLC; BIOSPECIFICS TECHNOLOGIES CORP.; BIOSPECIFICS TECHNOLOGIES LLC; DAVA INTERNATIONAL, LLC; DAVA PHARMACEUTICALS, LLC; ENDO GENERIC HOLDINGS, INC. (FORMERLY KNOWN AS PAR PHARMACEUTICALS COMPANIES, INC.); ENDO PHARMACEUTICALS INC.; ENDO PHARMACEUTICALS SOLUTIONS INC. (FORMERLY KNOWN AS INDEVUS PHARMACEUTICALS, INC.); GENERICS BIDCO I, LLC; GENERICS INTERNATIONAL (US), INC.; PAR PHARMACEUTICAL, INC.; PAR STERILE PRODUCTS, LLC (FORMERLY KNOWN AS JHP PHARMACEUTICALS, LLC); QUARTZ SPECIALTY PHARMACEUTICALS, LLC; SLATE PHARMACEUTICALS, LLC; VINTAGE PHARMACEUTICALS, LLC
Reel/Frame 067239/0795 →
RELEASE OF SECURITY INTEREST Recorded Apr 26, 2024
From: WILMINGTON TRUST, NATIONAL ASSOCIATION
To: ACTIENT PHARMACEUTICALS LLC; ASTORA WOMEN’S HEALTH HOLDINGS, LLC; ASTORA WOMEN’S HEALTH LLC; AUXILIUM PHARMACEUTICALS, LLC; AUXILIUM US HOLDINGS, LLC; BIOSPECIFICS TECHNOLOGIES CORP.; BIOSPECIFICS TECHNOLOGIES LLC; DAVA INTERNATIONAL, LLC; DAVA PHARMACEUTICALS, LLC; ENDO GENERIC HOLDINGS, INC. (FORMERLY KNOWN AS PAR PHARMACEUTICALS COMPANIES, INC.); ENDO PHARMACEUTICALS INC.; ENDO PHARMACEUTICALS SOLUTIONS INC. (FORMERLY KNOWN AS INDEVUS PHARMACEUTICALS, INC.); GENERICS BIDCO I, LLC; GENERICS INTERNATIONAL (US), INC.; PAR PHARMACEUTICAL, INC.; PAR STERILE PRODUCTS, LLC (FORMERLY KNOWN AS JHP PHARMACEUTICALS, LLC); QUARTZ SPECIALTY PHARMACEUTICALS, LLC; SLATE PHARMACEUTICALS, LLC; VINTAGE PHARMACEUTICALS, LLC
Reel/Frame 067239/0737 →
RELEASE OF SECURITY INTEREST Recorded Apr 25, 2024
From: WILMINGTON TRUST, NATIONAL ASSOCIATION
To: ACTIENT PHARMACEUTICALS LLC; ASTORA WOMEN’S HEALTH LLC; AUXILIUM PHARMACEUTICALS, LLC; AUXILIUM US HOLDINGS, LLC; BIOSPECIFICS TECHNOLOGIES CORP.; BIOSPECIFICS TECHNOLOGIES LLC; DAVA INTERNATIONAL, LLC; DAVA PHARMACEUTICALS, LLC; ENDO PHARMACEUTICALS INC.; ENDO PHARMACEUTICALS SOLUTIONS INC. (FORMERLY KNOWN AS INDEVUS PHARMACEUTICALS, INC.); GENERICS BIDCO I, LLC; GENERICS INTERNATIONAL (US), INC.; PAR PHARMACEUTICAL, INC.; PAR PHARMACEUTICAL COMPANIES, INC.; PAR STERILE PRODUCTS, LLC (FORMERLY KNOWN AS JHP PHARMACEUTICALS, LLC); QUARTZ SPECIALTY PHARMACEUTICALS, LLC; SLATE PHARMACEUTICALS, LLC; VINTAGE PHARMACEUTICALS, LLC
Reel/Frame 067239/0542 →
RELEASE OF SECURITY INTEREST Recorded Apr 25, 2024
From: WILMINGTON TRUST, NATIONAL ASSOCIATION
To: ACTIENT PHARMACEUTICALS LLC; ASTORA WOMEN’S HEALTH LLC; AUXILIUM PHARMACEUTICALS, LLC; AUXILIUM US HOLDINGS, LLC; BIOSPECIFICS TECHNOLOGIES CORP.; BIOSPECIFICS TECHNOLOGIES LLC; DAVA INTERNATIONAL, LLC; DAVA PHARMACEUTICALS, LLC; ENDO PHARMACEUTICALS INC.; ENDO PHARMACEUTICALS SOLUTIONS INC. (FORMERLY KNOWN AS INDEVUS PHARMACEUTICALS, INC.); GENERICS BIDCO I, LLC; GENERICS INTERNATIONAL (US), INC.; PAR PHARMACEUTICAL, INC.; PAR PHARMACEUTICAL COMPANIES, INC.; PAR STERILE PRODUCTS, LLC (FORMERLY KNOWN AS JHP PHARMACEUTICALS, LLC); QUARTZ SPECIALTY PHARMACEUTICALS, LLC; SLATE PHARMACEUTICALS, LLC; VINTAGE PHARMACEUTICALS, LLC
Reel/Frame 067239/0458 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Apr 23, 2024
From: BIOSPECIFICS TECHNOLOGIES LLC
To: ENDO USA, INC.
Reel/Frame 067198/0623 →
CHANGE OF NAME Recorded Jun 30, 2021
From: BIOSPECIFICS TECHNOLOGIES CORP.
To: BIOSPECIFICS TECHNOLOGIES LLC
Reel/Frame 056774/0545 →
CONFIRMATORY GRANT OF SECURITY INTEREST IN UNITED STATES PATENTS Recorded Apr 6, 2021
From: BIOSPECIFICS TECHNOLOGIES LLC; PAR PHARMACEUTICAL, INC.; AUXILIUM US HOLDINGS, LLC; ASTORA WOMEN'S HEALTH, LLC; ENDO PHARMACEUTICALS SOLUTIONS INC.; ENDO PHARMACEUTICALS, INC.
To: WILMINGTON TRUST, NATIONAL ASSOCIATION
Reel/Frame 055846/0246 →
CONFIRMATORY GRANT OF SECURITY INTEREST IN UNITED STATES PATENTS Recorded Apr 6, 2021
From: BIOSPECIFICS TECHNOLOGIES LLC; PAR PHARMACEUTICAL, INC.; AUXILIUM US HOLDINGS, LLC; ASTORA WOMEN'S HEALTH, LLC; ENDO PHARMACEUTICALS SOLUTIONS INC.; ENDO PHARMACEUTICALS, INC.
To: WILMINGTON TRUST, NATIONAL ASSOCIATION
Reel/Frame 055845/0618 →
SUPPLEMENT TO CONFIRMATORY GRANT OF SECURITY INTEREST IN UNITED STATES PATENTS Recorded Dec 14, 2020
From: BIOSPECIFICS TECHNOLOGIES CORP.
To: WILMINGTON TRUST, NATIONAL ASSOCIATION
Reel/Frame 054751/0412 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Dec 3, 2020
From: LEPPERT, PHYLLIS CAROLYN
To: DUKE UNIVERSITY
Reel/Frame 054534/0290 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Dec 3, 2020
From: WEGMAN, THOMAS L.; SOMA, JEAN-MARIE
To: BIOSPECIFICS TECHNOLOGIES CORP.
Reel/Frame 054534/0336 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Dec 3, 2020
From: SEGARS, JAMES H.
To: THE JOHNS HOPKINS UNIVERSITY
Reel/Frame 054534/0047 →
SUPPLEMENT TO CONFIRMATORY GRANT OF SECURITY INTEREST IN UNITED STATES PATENTS Recorded Dec 2, 2020
From: BIOSPECIFICS TECHNOLOGIES CORP.
To: WILMINGTON TRUST, NATIONAL ASSOCIATION
Reel/Frame 054575/0678 →