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-11518782-B2
Publication Date
2022-12-06
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 relates to hyaluronan (HA) complexes that include pentraxin 3 (PTX3) and inter-α-inhibitor heavy chain 1 (HC1), comprising native and reconstituted HC-HA/PTX3 complexes. The reconstituted complex (rcHC-HA/PTX3) is formed by immobilized high molecular weight hyaluronan (HMW-HA) and PTX3 followed by transfer of IαI (HC1) catalyzed by TSG-6, and the native HC-HA/PTX3 complex (nHC-HA/PTX3) is described as a related composition basis.
The complexes are described as functional immunomodulatory compositions that promote macrophage polarization toward an M2 phenotype and upregulate IL-10 under LPS-stimulated conditions. In the same conditions, they reduce pro-inflammatory cytokine expression, including IL-12p40, IL-12p70, and IL-23, and they induce apoptosis and enhance phagocytosis of apoptotic neutrophils.
The complexes are also described as supporting macrophage attachment behavior, including CD44/TLR4-mediated attachment on immobilized complexes. The document presents composition and application scope for anti-inflammatory activity, anti-scarring/anti-fibrosis activity, and additional therapeutic themes including anti-angiogenesis, anti-adhesion, and tissue regeneration, and it discusses pharmaceutical formulations, device coatings, combinations/kits, and preparation from fetal tissues such as amnion and umbilical cord.
Claims Coverage
The independent claim coverage centers on a method for reducing scarring that administers a therapeutically effective amount of a composition containing a reconstituted Heavy Chain–Hyaluronan/pentraxin 3 (rcHC-HA/PTX3) complex with a pharmaceutically acceptable excipient, using topical administration, injection, infusion, or implantation. Two inventive features are consistently present across the independent claim coverage: the rcHC-HA/PTX3 composition for scarring reduction and the permitted administration modes.
Reconstituted heavy chain-hyaluronan/pentraxin 3 complex for scarring reduction
A method of reducing scarring in an individual in need thereof by administering a therapeutically effective amount of a composition comprising a reconstituted Heavy Chain-Hyaluronan/pentraxin 3 (rcHC-HA/PTX3) complex and a pharmaceutically acceptable excipient.
Administration by topical administration, injection, infusion, or implantation
The method wherein administering is by topical administration, injection, infusion, or implantation.
Across the independent claim coverage, the core inventive concept is a scarring-reduction method that depends on administering a therapeutically effective amount of a composition containing a reconstituted HC-HA/PTX3 complex together with a pharmaceutically acceptable excipient, using topical administration, injection, infusion, or implantation.
Stated Advantages
Reduces scarring.
Promotes M2 macrophage polarization and IL-10 upregulation in LPS-stimulated conditions.
Reduces pro-inflammatory cytokine expression, including IL-12p40, IL-12p70, and IL-23.
Induces apoptosis and enhances phagocytosis of apoptotic neutrophils.
Supports macrophage attachment behavior, including CD44/TLR4-mediated attachment on immobilized complexes.
Therapeutic activity directed to anti-inflammatory and anti-scarring/anti-fibrosis themes.
Documented therapeutic/application scope includes anti-angiogenesis, anti-adhesion, and tissue regeneration themes.
Documented Applications
Reducing scarring in an individual in need thereof, including dry eye scarring associated with chronic graft-versus-host disease.
Co-administration with cells and tissue transplants, including stem cell transplant contexts, together with immunosuppressive agents.
Coating or treating organs, tissues, or stem cells to shield from host immunity and to reduce inflammatory effects.
Anti-inflammatory use based on immunomodulatory effects described in LPS-stimulated conditions.
Anti-scarring/anti-fibrosis application theme.
Anti-angiogenesis, anti-adhesion, and tissue regeneration application themes.
Pharmaceutical compositions and device coatings are described as part of the therapeutic/application scope.
Combinations/kits are described as part of the therapeutic/application scope, including optional co-administration of an additional therapeutic agent.
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