Cartilage-homing peptides

Patent metadata

Field	Value
Publication number	US-2022016202-A1
Application number	US-202117353447-A
Country	US
Kind code	A1
Filing date	Jun 21, 2021
Priority date	Sep 9, 2015
Publication date	Jan 20, 2022
Grant date	—

Abstract

Peptides that home, target, migrate to, are directed to, are retained by, or accumulate in and/or binds to the cartilage of a subject are disclosed. Pharmaceutical compositions and uses for peptides or peptide-active agent complexes comprising such peptides are also disclosed. Such compositions can be formulated for targeted delivery of a drug to a target region, tissue, structure or cell in the cartilage. Targeted compositions of the disclosure can deliver peptide or peptide-active agent complexes to target regions, tissues, structures or cells targeted by the peptide.

First claim

1 .- 118 . (canceled)

119 . A knotted peptide comprising a sequence having at least 90% sequence identity to SEQ ID NO: 325.

120 . The knotted peptide of claim 119 , wherein the knotted peptide 4 or more cysteine residues and a plurality of disulfide bridges formed between cysteine residues.

121 . The knotted peptide of claim 119 , wherein the knotted peptide homes, targets, migrates to, accumulates in, binds to, is retained by, or is directed to a cartilage.

122 . The knotted peptide of claim 119 , wherein the knotted peptide has a sequence of SEQ ID NO: 325.

123 . The knotted peptide of claim 119 , wherein the knotted peptide is linked to an active agent.

124 . The knotted peptide of claim 123 , wherein the active agent comprises a therapeutic agent, a detectable agent, or a combination thereof.

125 . The knotted peptide of claim 124 , wherein the therapeutic agent comprises a therapeutic small molecule.

126 . The knotted peptide of claim 124 , wherein the therapeutic agent comprises an antibiotic, an anti-viral agent, an anti-fungal agent, an anti-inflammatory agent, a protease inhibitor, an immune modulator, an anti-cytokine agent, a tyrosine kinase inhibitor, a growth factor, a cytotoxic T-lymphocyte-associated protein 4 (CTLA4) inhibitor, a B-cell lymphoma 2 (BCL-2) family inhibitor, a tumor necrosis factor alpha (TNF-α) modulator, a tumor necrosis factor receptor (TNFR) family modulator, or any combination thereof.

127 . The knotted peptide of claim 126 , wherein the anti-inflammatory agent comprises a steroid or a nonsteroidal anti-inflammatory drug (NSAID).

128 . The knotted peptide of claim 127 , wherein the steroid is a corticosteroid or a glucocorticoid.

129 . The knotted peptide of claim 127 , wherein the steroid is triamcinolone acetonide, dexamethasone, budesonide, triamcinolone, cortisone, prednisone, rednisolone, triamcinolone hexacetonide, or methylprednisolone.

130 . The knotted peptide of claim 127 , wherein the NSAID is ibuprofen, naproxen, ketorolac, indomethacin, etodolac, tolemetin, celecoxib, aceclofenac, nabumetone, sulindac, or diclofenac.

131 . The knotted peptide of claim 126 , wherein the protease inhibitor is a matrix metalloprotease 13 (MMP13) inhibitor.

132 . The knotted peptide of claim 124 , wherein the therapeutic agent comprises imatinib mesylate or methotrexate.

133 . The knotted peptide of claim 124 , wherein the therapeutic agent comprises a therapeutic peptide.

134 . The knotted peptide of claim 133 , wherein the therapeutic peptide is a cytokine, an enzyme, a growth factor, a chemokine, a neurotransmitter, an Fc region, or any combination thereof.

135 . The knotted peptide of claim 124 , wherein therapeutic agent comprises an antibody or an antibody fragment.

136 . The knotted peptide of claim 124 , wherein the detectable agent comprises a fluorophore, a metal, a metal chelate, an X-ray contrast agent, a PET agent, a radioisotope, a photosensitizer, a radiosensitizer, a radionuclide chelator, or any combination thereof.

137 . A pharmaceutical composition comprising the knotted peptide of claim 119 and a pharmaceutically acceptable carrier.

138 . The pharmaceutical composition of claim 137 , wherein the pharmaceutical composition is formulated for inhalation, intranasal administration, oral administration, intravenous administration, subcutaneous administration, intra-articular administration, intramuscular administration, intraperitoneal administration, administration locally into an affected area, administration into a joint, or any combination thereof.

139 . A method of labeling an organ or a body region in a subject, the method comprising:
administering to the subject a composition comprising a knotted peptide linked to a detectable agent, wherein the knotted peptide comprises a sequence having at least 90% sequence identity to SEQ ID NO: 325; thereby labeling the organ or the body region in the subject.

140 . A method of treating a disease or condition in a subject, the method comprising:
administering to the subject a composition comprising a knotted peptide linked to a therapeutic agent, wherein the knotted peptide comprises a sequence having at least 90% sequence identity to SEQ ID NO: 325; thereby treating the disease or condition in the subject.

141 . The method of claim 140 , wherein the knotted peptide homes, targets, or migrates to cartilage of the subject following administration.

142 . The method of claim 140 , wherein the disease or condition is associated with a function of cartilage.

143 . The method of claim 140 , wherein the disease or condition is lupus, a type of arthritis, bursitis, tendinitis, gout, pseudogout, an arthropathy, inflammation, a cancer, degradation, a growth disturbance, genetic, a tear, an infection, an injury, a chondrodystrophy, a traumatic rupture or detachment, a costochondritis, a herniation, a polychondritis, a chordoma, achondroplasia, a benign chondroma, or a malignant chondrosarcoma.

144 . The method of claim 143 , wherein the type of arthritis is osteoarthritis, rheumatoid arthritis, ankylosing spondylitis, or psoriatic arthritis.

Assignees

• Hutchinson Fred Cancer Res
• Blaze Bioscience Inc

Inventors

• Olson James
• Strand Andrew David
• Girard Emily June
• Strong Roland
• Mehlin Christopher
• Correnti Colin
• Nairn Natalie

Classifications

• A61P19/04

  for non-specific disorders of the connective tissue · CPC title

• A61K49/0032

  Methine dyes, e.g. cyanine dyes · CPC title

• A61K51/08

  Peptides, e.g. proteins {, carriers being peptides, polyamino acids, proteins} · CPC title

• A61K38/17 Primary

  from animals; from humans {(enzyme inhibitors A61K38/005)} · CPC title

• A61K49/0056 Primary

  Peptides, proteins, polyamino acids · CPC title