Use of c-type natriuretic peptide variants to treat osteoarthritis
Inventors
O'Neill, Charles A. • OPPENEER, TODD M. • Pinkstaff, Jason K.
Assignees
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Publication Number
US-12214015-B2
Publication Date
2025-02-04
Expiration Date
Abstract
The disclosure relates to the use of variants of C-type natriuretic peptide (CNP) to treat osteoarthritis, to ameliorate one or more symptoms of osteoarthritis, and to treat disorders having an osteoarthritis component.
Core Innovation
The patent describes methods of treating osteoarthritis in a subject by intraarticularly administering a composition comprising a C-type natriuretic peptide (CNP) variant. It describes CNP variants, including sequence-defined CNP-37 variants such as Gly-CNP-37 and Pro-Gly-CNP-37, and compositions related to producing and using those variants. The disclosure is directed to osteoarthritis pathology involving degeneration and cartilage architecture, including targeting degeneration/cartilage rather than only inflammation.
The patent further describes outcomes associated with administration of CNP variant peptides and compositions, including increased cartilage growth, reduced cartilage degeneration, increased calcified cartilage and subchondral bone growth, increased range of motion, reduced stiffness, reduced synovial inflammation, and reduced osteophyte growth. It also reports reduction of cartilage degeneration, improvements in mobility or gait, and reduction of osteophyte measures.
The disclosure additionally addresses engineering strategies intended to extend half-life and retain function by reducing NEP and/or NPR-C susceptibility, increasing NEP resistance through amino acid and peptide bond modifications at NEP-cleavage-related positions, reducing albumin binding through sequence/charge/pI control and polymer conjugation, and optional conjugations such as PEG/PEO, chimera/fusion proteins, and cleavable peptide/protein tags for delivery considerations.
Claims Coverage
The partial content provides three independent claims. Across these claims, the inventive features focus on intraarticular administration of enumerated CNP variants at a defined dose range to achieve osteoarthritis and joint-structure outcomes.
Intraarticular CNP variant treatment of osteoarthritis
A method of treating osteoarthritis in a subject by intraarticularly administering a composition comprising a C-type natriuretic peptide (CNP) variant at a dose of from 5 μg/kg to 800 μg/kg, where the CNP variant is selected from an enumerated group of sequence-defined CNP-37 variants.
Increasing cartilage growth or slowing cartilage degeneration
A method of increasing cartilage growth or slowing cartilage degeneration in a subject having osteoarthritis by intraarticularly administering a composition comprising a C-type natriuretic peptide (CNP) variant at a dose of from 5 μg/kg to 800 μg/kg, where the CNP variant is selected from an enumerated group of sequence-defined CNP-37 variants.
Reducing osteophyte growth
A method of reducing osteophyte growth in a subject having osteoarthritis or having an injury or trauma in a joint by intraarticularly administering a composition comprising a C-type natriuretic peptide (CNP) variant at a dose of from 5 μg/kg to 800 μg/kg, where the CNP variant is selected from an enumerated group of sequence-defined CNP-37 variants.
Across the independent claims, the shared inventive framework is intraarticular administration of a composition containing an enumerated CNP variant within a specified dose range, used to treat osteoarthritis, increase cartilage growth or slow cartilage degeneration, and reduce osteophyte growth in osteoarthritis and/or in a subject with joint injury or trauma.
Stated Advantages
Reduction of cartilage degeneration.
Improvements in mobility or gait.
Reduced osteophyte measures.
Decreased synovial inflammation in the subject.
Increases cartilage/calcified cartilage/subchondral bone growth or reduces cartilage degeneration.
Increases range of motion and reduces joint stiffness.
Reduces synovial inflammation.
Reduces osteophyte growth.
Documented Applications
Treating osteoarthritis in a subject by intraarticular administration of a composition comprising a C-type natriuretic peptide (CNP) variant.
Osteoarthritis treatment by intraarticular administration of a composition comprising a C-type natriuretic peptide (CNP) variant, including outcomes related to cartilage degeneration, osteophyte measures, and synovial inflammation.
Increasing cartilage growth or slowing cartilage degeneration in a subject having osteoarthritis.
Reducing osteophyte growth in a subject having osteoarthritis or having an injury or trauma in a joint.
Rat osteoarthritis model studies using Gly-CNP-37 and Pro-Gly-CNP-37, including intraarticular versus subcutaneous regimens and reported pharmacokinetic/pharmacodynamic observations [procedural detail omitted for safety].
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