Extended local release of anti-CSFR1 antibodies
Inventors
Alani, Laman • Hsu, Chung-Chiang • Johnson, Kirk William
Assignees
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-11427641-B2
Publication Date
2022-08-30
Expiration Date
Abstract
The present disclosure provides compositions and methods for extended release of certain types of antibodies in vivo. It was discovered that such antibodies are able to initiate reversible gelation of hyaluronic acid (HA) by creating a depot that dissociates over time to release the antibody without any impact on its physical and chemical properties as well as its biological activity. As certain tissues and organs, such as eyes, joints and skins, contain HA, local injection of the antibodies to these tissues or organs will result in embedding of the antibody in gel formed from the HA, which becomes a repository of slow-released antibodies. In addition, slow-released formulations can be prepared with antibodies mixed with HA, optionally with other polymers.
Core Innovation
The invention provides extended release of an antibody in a mammalian subject by injection of an aqueous solution comprising at least 15 mg/mL of the antibody to or near a tissue that contains hyaluronic acid (HA). The antibody reversibly forms gel with HA, producing an extended release depot associated with HA gelation and subsequent slow dissociation/erosion described in the disclosure.
In one embodiment, the antibody is AM001, where AM001 comprises a heavy chain comprising the amino acid sequence of SEQ ID NO:7 and a light chain comprising the amino acid sequence of SEQ ID NO:8. The aqueous solution has a pH between 4.5 and 5.5 and includes less than 100 mM of an alkaline salt or a salt of an amino acid. The document describes that these formulation conditions enable the antibody to reversibly form gel with HA.
In another embodiment, the antibody is Emactuzumab. The aqueous solution has a pH between 5.5 and 6.5 and includes less than 100 mM of an alkaline salt or a salt of an amino acid. The disclosure further states that when injected to or near HA-containing tissues, the antibody reversibly forms gel with HA to provide extended release.
The document also describes that the extended release is tied to HA-containing tissues such as eyes, joints, and skin/dermis, including local injection to produce a gel-like depot with endogenous HA. Supporting experiments in the disclosure report HA-driven reversible gelation/precipitation in vitro and extended release/CSF1R inhibition plateau in vivo, with loss of activity/integrity avoided as described in the disclosure.
Claims Coverage
The independent claims are clm-00001 and clm-00002. Each independent claim recites a method of providing extended release by local injection into/near HA-containing tissue with reversible HA gel formation, with additional inventive features specifying the particular antibody and formulation pH and salt constraints; a total of multiple inventive features are present across the two independent claims.
Extended release via HA reversibly forming gel depot
The method comprises injection of an aqueous solution comprising at least 15 mg/mL of the antibody to or near a tissue in a mammalian subject, where the tissue contains hyaluronic acid (HA) and the antibody reversibly forms gel with HA.
AM001 formulation enabling HA reversible gel formation
The antibody is AM001 comprising a heavy chain comprising the amino acid sequence of SEQ ID NO:7 and a light chain comprising the amino acid sequence of SEQ ID NO:8, and the aqueous solution has a pH between 4.5 and 5.5 and includes less than 100 mM of an alkaline salt or a salt of an amino acid.
Emactuzumab formulation enabling HA reversible gel formation
The antibody is Emactuzumab and the aqueous solution has a pH between 5.5 and 6.5 and includes less than 100 mM of an alkaline salt or a salt of an amino acid.
Across the independent claims, extended release is provided by injecting a concentrated antibody solution to or near HA-containing tissue such that the antibody reversibly forms gel with HA. Claim clm-00001 further requires AM001 with specified heavy and light chain sequences and a pH between 4.5 and 5.5 with less than 100 mM alkaline/amino-acid salt, while claim clm-00002 requires Emactuzumab with a pH between 5.5 and 6.5 and less than 100 mM alkaline/amino-acid salt.
Stated Advantages
Provides extended release of an antibody in a mammalian subject via reversible HA gel formation.
Enables prolonged antibody release without loss of activity/integrity as described in the disclosure.
Produces an extended release/extended half-life with sustained CSF1R inhibition plateau as described in the disclosure.
Documented Applications
Local injection into HA-containing tissues including eyes (e.g., intravitreal), joints (e.g., intra-articular), and skin/dermis (e.g., subcutaneous) to provide extended release.
Treatment context described with CSF1/CSF1R biology including tenosynovial giant cell tumor (TGCT) as referenced in the disclosure.
Interested in licensing this patent?