Granted Patent B2

US 12,622,945 · App. 18/242,406 · Granted May 12, 2026

Inventors: Yoshinari Kumagai (Foster City, CA); Dawn McGuire (Orinda, CA); Meghan Miller (Antioch, CA); David Rosen (New Braunfels, TX)

Assignee: OrthoTrophix, Inc.

A61K38/16A61B5/055A61B5/4504A61B5/4848A61B6/032A61B6/505A61B8/0875A61K9/0019A61K38/18A61P19/02

Abstract

Claims (21)

1 . A method of determining efficacy of a peptide comprising:

(a) testing and confirming that the peptide binds integrin α v β 3 expressed on osteocytes, wherein the binding affinity of the peptide to integrin α v β 3 expressed on osteocytes is found to be at least 300 times higher than its binding affinity to the integrins α v β 1 , α v β 6 , α v β 8 , α 1 β 1 , α 2 β 1 , α 3 β 1 , α 4 β 1 , α 5 β 1 , α 6 β 1 , α 8 β 1 , α 9 β 1 , and α 10 β 1 and wherein the peptide is found to bind integrin α v β 5 with a lower affinity than the peptide's affinity to integrin α v β 3 ,

(b) testing and confirming that the peptide is agonistic on binding to integrin α v β 3 expressed on osteocytes, and is not antagonistic, inhibitory, or blocking; and

(c) injecting a subject with the peptide confirmed in step (a) to potentially be efficacious and thereby determining if binding to integrin α v β 3 is at a level so as to result in improving joint function upon injection into a subject;

(d) testing and confirming that the peptide binding to integrin α v β 3 expressed on osteocytes is at a level so as to result in improving joint function upon injection into a subject.

2 . The method of claim 1 , further comprising:

(e) measuring 3D bone shape change by obtaining a bone image of the subject injected in (c) and analyzing the image with an algorithm which calculates the 3D bone shape, and wherein the 3D bone shape is determined by a B-score, wherein the algorithm is based on active appearance modeling (AAM).

3 . The method of claim 2 , further comprising:

(f) determining if the injecting results in impacting a change of three-dimensional (3D) bone shape in the subject.

4 . The method of claim 3 , further comprising:

(g) continuing the injecting of the subject at different points in time and determining if the peptide delays, arrests, or reverses 3D bone shape change in the subject.

5 . The method of claim 4 , further comprising:

(h) determining if the 3D bone shape change occurs in a joint of the subject.

6 . The method of claim 5 , wherein the 3D bone shape change occurs in a knee joint.

7 . The method of claim 5 , wherein the 3D bone shape change in the joint is determined to be associated with natural aging.

8 . The method of claim 5 , wherein the 3D bone shape change in the joint is determined to be pathological.

9 . The method of claim 5 , wherein the 3D bone shape change in the joint is associated with one or more of osteoarthritis, rheumatoid arthritis, trauma, osteoporosis, disc herniation, spinal injury, or temporomandibular disorder; and

wherein the 3D bone shape change occurs in one or more of the joints of knee, hip, ankle, toe, finger, hand, wrist, elbow, shoulder, spine, or jaw.

10 . The method of claim 2 , wherein the bone image is obtained using imaging technology selected from the group consisting of magnetic resonance (MR), radiography (X-ray), computer tomography (CT) and ultrasound.

11 . The method of claim 8 , wherein the peptide reduces a pathological event selected from the group consisting of excessive mineralization of the bone, and excessive bone sclerosis.

12 . The method of claim 1 , wherein the peptide binds to integrin α v β 3 at a binding affinity at least three (3) times higher than its binding affinity to the integrin α v β 5 .

Assignments (1)

Continuity (6)

References Cited (73)