Compositions containing HC-HA/PTX3 complexes and methods of use thereof
Inventors
Tseng, Scheffer • He, Hua • Tighe, Sean • Zhang, Suzhen • Zhu, Ying-Tieng
Assignees
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Publication Number
US-10253065-B2
Publication Date
2019-04-09
Expiration Date
Abstract
Provided herein are methods for the production of native and reconstituted hyaluronan (HA) complexes containing pentraxin-3 (PTX3) and heavy chain 1 (HC1) of inter alpha inhibitor (IαI). Compositions containing the complexes and therapeutic methods using the complexes are provided. Combinations and kits for use in practicing the methods also are provided.
Core Innovation
The invention concerns reconstituted HC-HA/PTX3 complexes comprising hyaluronic acid (HA), heavy chain 1 (HC1) and heavy chain 2 (HC2) of inter-alpha-inhibitor (IαI), and pentraxin 3 (PTX3). The complexes are described as native and in-vitro reconstituted HA complexes, including complexes obtained from fetal tissues, amniotic membrane, and umbilical cord tissues.
The patent further describes biochemical preparation and assembly of these complexes from PTX3, TSG-6, IαI components, and HA, including recombinant or cell-free production approaches. It also describes PTX3 multimerization, use of TSG-6 fragments and the link module of TSG-6 for HC1-to-HA transfer, and purification of rcHC-HA/PTX3 complexes using chromatography and immunoaffinity or affinity methods involving antibodies or HA binding proteins.
The document connects these compositions to immune modulation, anti-inflammatory activity, anti-scarring and anti-fibrosis, including reduction of TGF-β signaling. Additional described formats include HA immobilization on solid support, device- and surface-immobilized complex formats, and associated kits, pharmaceutical compositions, and ocular delivery formulations.
Claims Coverage
The independent claim coverage is directed to reducing inflammation by administering a therapeutically effective amount of a composition containing a reconstituted HC-HA/PTX3 complex together with one or more formulation components. The consolidated coverage includes two core inventive features: the specific rcHC-HA/PTX3 complex composition and its use in an inflammation-reducing therapeutic composition, with dependent refinements for ocular and scar-related contexts.
Reconstituted hc-ha/ptx3 complex for inflammation reduction
A method of reducing inflammation by administering a therapeutically effective amount of a composition comprising a reconstituted HC-HA/PTX3 complex comprising hyaluronic acid (HA), heavy chain 1 (HC1) and heavy chain 2 (HC2) of inter-alpha-inhibitor (IαI), and pentraxin 3 (PTX3).
Formulation components included with the rc-hc-ha/ptx3 complex
The composition further comprises a natural polymer, adjuvant, excipient, preservative, agent for delaying absorption, filler, binder, adsorbent, buffer, or combination thereof together with the rcHC-HA/PTX3 complex for reducing inflammation.
Ocular administration to an eye or tissue adjacent to an eye
The method where the composition is administered to the eye, or to tissue adjacent to an eye.
Ocular delivery by topical administration or injectable depot preparation
The method where the composition is administered to the eye either by topical administration or as an injectable depot preparation.
Preventing or reversing scar formation
The method characterized such that the composition prevents or reverses scar formation.
Overall, the claims are centered on administering an inflammation-reducing composition that combines a reconstituted HC-HA/PTX3 complex with specified formulation components, with dependent refinements addressing ocular administration, route options, and scar formation prevention or reversal.
Stated Advantages
Reduces inflammation.
Prevents or reverses scar formation.
Documented Applications
Anti-inflammatory and anti-scarring effects across multiple animal disease models.
Ocular use including administration to an eye or to tissue adjacent to an eye, and ocular delivery by topical administration or injectable depot preparation.
Stem cell expansion and pluripotency induction contexts in which TGF-β suppression and BMP activation are described, including reduced transcription factors needed for iPSC induction.
In vitro mechanistic studies related to macrophage polarization and immune marker outcomes, including macrophage M1/M2 markers and cytokine profiles.
Anti-inflammatory treatment across multiple inflammatory disorders, including ocular applications.
Therapeutic use directed to macrophage M2 polarization, including reduced IL-12p40, IL-12p70, IL-23 and increased IL-10.
Induction of neutrophil apoptosis and enhanced phagocytosis of apoptotic neutrophils.
Anti-scarring and anti-fibrosis via reduction of TGF-β signaling.
Angiogenesis modulation.
Stem cell maintenance, expansion, and pluripotency.
Immobilized complex formats, including device- and surface-immobilized complexes.
Kits and pharmaceutical compositions containing the complexes.
Treatment contexts involving scar formation, including preventing or reversing scar formation.
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