Recombinant nucleic acids encoding cosmetic protein(s) for aesthetic applications

Inventors

Krishnan, Suma • PARRY, Trevor • Agarwal, Pooja

Assignees

Krystal Biotech Inc

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Publication Number

US-10786438-B2

Patent

Publication Date

2020-09-29

Expiration Date


Abstract

The present disclosure provides recombinant nucleic acids comprising one or more polynucleotides encoding one or more cosmetic proteins (e.g., one or more human collagen proteins); viruses comprising the recombinant nucleic acids; compositions (e.g., cosmetic formulations) comprising the recombinant nucleic acids and/or viruses; methods of their use; and articles of manufacture or kits thereof.

Core Innovation

The disclosure relates to pharmaceutical compositions for topical, transdermal, superficial, or intradermal administration that include a herpes simplex virus comprising a recombinant herpes simplex virus genome. The recombinant genome encodes a first polynucleotide for a first cosmetic protein and a second polynucleotide for a second cosmetic protein, together with a pharmaceutically acceptable excipient. The recombinant herpes simplex virus genome includes an inactivating mutation in both copies of the ICP4 herpes simplex virus gene and does not comprise a polynucleotide encoding a Collagen alpha-1 (VII) chain polypeptide (COL7).

The first cosmetic protein is selected from collagen proteins, fibronectin, elastin, lumican, vitronectin, a vitronectin receptor, laminin, neuromodulator, and fibrillin proteins. The document also characterizes variants that are replication-defective and/or have reduced cytotoxicity as compared to corresponding wild-type herpes simplex virus. HSV-1/HSV-2 selection and additional inactivating mutation targets such as ICP0, ICP22, ICP27, and ICP47 are described as refinements.

The invention further frames a method of improving skin condition, quality, and/or appearance in a subject. The method administers an effective amount of the pharmaceutical composition to the subject such that the recombinant herpes simplex virus genome is delivered to one or more target cells of the skin and the cosmetic protein is expressed in one or more target cells of the skin. The disclosed compositions are directed to skin delivery contexts, including topical, transdermal, intradermal, and superficial injection.

Claims Coverage

The independent claims are directed to a pharmaceutical composition and a method for improving skin condition, quality, and/or appearance. Across the claims, the main inventive features include recombinant HSV genome engineering for cosmetic-protein expression, ICP4 inactivation in both copies, exclusion of COL7, and skin-directed administration with delivery to skin target cells and expression in those cells.

Topical, transdermal, superficial, or intradermal recombinant HSV cosmetic protein composition

A pharmaceutical composition for topical, transdermal, superficial, or intradermal administration comprising a herpes simplex virus comprising a recombinant herpes simplex virus genome with a first polynucleotide encoding a first cosmetic protein and a second polynucleotide encoding a second cosmetic protein, and a pharmaceutically acceptable excipient.

Icp4 double-copy inactivating mutation

The recombinant herpes simplex virus genome comprises an inactivating mutation in both copies of the ICP4 herpes simplex virus gene.

No COL7 polynucleotide in the recombinant genome

The recombinant herpes simplex virus genome does not comprise a polynucleotide encoding a Collagen alpha-1 (VII) chain polypeptide (COL7).

Skin target cell delivery and cosmetic protein expression

The method comprises administering to the subject an effective amount of a pharmaceutical composition in which the recombinant herpes simplex virus genome is delivered to one or more target cells of the skin of a subject and the first cosmetic protein is expressed in one or more target cells of the skin of a subject.

Skin condition, quality, and appearance improvement

A method of improving skin condition, quality, and/or appearance in a subject by administering a pharmaceutical composition comprising a herpes simplex virus with a recombinant herpes simplex virus genome encoding a first cosmetic protein and a second cosmetic protein, with ICP4 double-copy inactivation and without a COL7-encoding polynucleotide.

The independent claims converge on recombinant herpes simplex virus genomes engineered for skin delivery of one or more cosmetic proteins, with an inactivating mutation in both copies of ICP4 and a deliberate exclusion of a COL7-encoding polynucleotide, while the method further requires delivery to skin target cells and expression of the cosmetic protein in those cells.

Stated Advantages

Reduced cytotoxicity as compared to a corresponding wild-type herpes simplex virus.

Replication-defective and/or reduced cytotoxicity as compared to corresponding wild-type herpes simplex virus.

Documented Applications

Improving skin condition, quality, and/or appearance in a subject.

Administration as a cosmetic composition via topical, transdermal, intradermal, or superficial injection to deliver and express cosmetic proteins in skin target cells.

Topical, transdermal, superficial, or intradermal administration to skin target cells.

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