Researchers Submit Patent Application, “Compositions And Methods For Treatment Of Skin Disorders”, for Approval (USPTO 20220323513): Patent Application

2022 NOV 01 (NewsRx) -- By a News Reporter-Staff News Editor at Insurance Daily News -- From Washington, D.C., NewsRx journalists report that a patent application by the inventors HANZEL, David (Palo Alto, CA, US); TAYLOR, Emma (San Francisco, CA, US), filed on November 18, 2021, was made available online on October 13, 2022.

No assignee for this patent application has been made.

News editors obtained the following quote from the background information supplied by the inventors: “The community of microorganisms living on and/or within an individual is the microbiome. The microbiome consists of many different bacterial species some of which are beneficial, neutral or deleterious to human health. Alterations in the microbiome have been connected to many disease states such as inflammatory diseases, metabolic disease, developmental diseases, psychological diseases and cancer. Determining the composition of the microbiome, and altering the microbiome from a pathological to healthy state holds great therapeutic promise for many different diseases.”

As a supplement to the background information on this patent application, NewsRx correspondents also obtained the inventors’ summary information for this patent application: “Provided herein are microbiome-based approaches to skin therapy using beneficial bacteria on the skin to eliminate or reduce harmful bacteria and restore skin to a healthy state. The methods and compositions disclosed herein may be used for a wide range of skin disorders including acne, eczema, psoriasis, rosacea and seborrheic dermatitis. Problems with current treatments for these disorders include antibiotic resistance, side effects, complicated regimens, and lack of long-term effectiveness. Treatments disclosed herein may provide alternatives to antibiotics, use healthy bacteria, present few side effects, with simple treatment regimens and long-term effectiveness.

“Compositions described herein generally contain at least one health-associated microbe or probiotic that conveys beneficial effects to a subject with a skin disorder. Thus, the compositions disclosed herein are effective on the skin (e.g., at skin temperature). These compositions sometimes contain a mixture of several strains that have each been isolated, purified, selected or engineered to provide a specific cocktail of bacteria that does not occur in nature. These strains can be stored or packaged with a preservative agent, such as glycerol or polyethylene glycol in a container or on an applicator such as a cotton swab, as shown in FIG. 1. These containers and applicators can be stored in a freezer, refrigerator or on a shelf at room temperature, both before and during use.

“Many of the compositions and methods disclosed herein comprise bacteria known as Propionibacterium acnes, abbreviated P. acnes, and uses thereof, respectively. However, other bacteria, including genetically modified strains, and uses thereof are also contemplated herein. Some strains of P. acnes used in compositions and methods disclosed herein are referred to herein as healthy strains of P. acnes or, for simplicity, “healthy P. acnes.” Healthy strains of P. acnes generally promote skin health by preventing a skin disorder or reducing symptoms of a skin disorder. Healthy strains of P. acnes may even promote skin health by eliminating the cause of a skin disorder. Other strains of P. acnes are referred to herein as pathogenic strains or “pathogenic P. acnes.” Pathogenic P. acnes generally promote or cause a skin disorder or symptoms thereof. Generally, pathogenic P. acnes are not used in compositions and methods described herein. Instead, methods and compositions disclosed herein may be useful in reducing or preventing growth of pathogenic P. acnes on the skin of a subject. In some cases, an amount of P. acnes can be considered healthy or pathogenic, too much or too little being desirable or undesirable. In some cases, a combination of multiple P. acnes strains confers health. Conversely, in some cases, a different combination of multiple P. acnes strains can be pathogenic. Strains of P. acnes, combinations thereof, and amounts thereof that are healthy and pathogenic are described herein.

“Compositions and methods disclosed herein may comprise bacteria with a given genetic signature and uses thereof, respectively. While P. acnes is the bacteria primarily exemplified herein, it is contemplated that other bacteria having a particular genetic signature that is similar to healthy P. acnes could likewise be useful for compositions and methods disclosed herein. For example, many P. acnes strains that are identified as healthy herein comprise a combination of a deoxyribose operon repressor (deoR), a type II lipase, and a CRISPR associated Cas endonuclease. Additionally, healthy P. acnes strains are generally associated with an absence or only small amounts of an extrachromosomal plasmid known in the art as pIMPLE plasmids. It has previously been reported that some strains of P. acnes harbor an extrachromosomal plasmid, given the term, “pIMPLE plasmid,” by those in the field. Such plasmids are readily found in the art. pIMPLE plasmids may have multiple open reading frames (ORFs). The presence of these aforementioned genes (e.g., deoR, lipase, Cas) and/or a low presence of pIMPLE plasmid may provide a healthy skin promoting genetic signature that can be used to identify bacteria other than P. acnes that are useful in compositions and methods of treating acnes described herein.

“In some aspects, disclosed herein are pharmaceutical compositions that comprise: a first therapeutically effective amount of a first health-associated Propionibacterium microbe, wherein the first health-associated Propionibacterium microbe produces less than about one micromolar porphyrin; a second therapeutically effective amount of a second health-associated microbe; and a pharmaceutically acceptable excipient or biological stabilizer. In some embodiments, the second health-associated microbe comprises a strain of Propionibacterium. In some embodiments, the second health-associated microbe produces less than about one micromolar porphyrin. In some embodiments, the first health-associated Propionibacterium microbe and the second health-associated Propionibacterium microbe collectively produce less than about one micromolar porphyrin. In some embodiments, at least one of the first health-associated Propionibacterium microbe and the second health-associated Propionibacterium microbe produce less than about 200 nM porphyrin. In some embodiments, at least one of the first health-associated Propionibacterium microbe and the second health-associated Propionibacterium microbe produce less than about 100 nM porphyrin. In some embodiments, the first health-associated Propionibacterium microbe and the second health-associated Propionibacterium microbe collectively produce less than about 100 nM porphyrin. In some embodiments, at least one of the first health-associated Propionibacterium microbe and the second health-associated Propionibacterium microbe produce less than about one micromolar porphyrin in situ. In some embodiments, at least one of the first health-associated Propionibacterium microbe and the second health-associated Propionibacterium microbe produce less than about one micromolar porphyrin in vitro. In some embodiments, at least the first health-associated Propionibacterium microbe comprises a strain of Propionibacterium acnes, Propionibacterium granulosum, Propionibacterium avidum, or Propionibacterium acnes subsp. defendens. In some embodiments, at least the first health-associated Propionibacterium microbe comprises a strain of Propionibacterium acnes. In some embodiments, at least the first health-associated Propionibacterium microbe comprises a Propionibacterium acnes of a ribotype RT1 or RT2. In some embodiments, at least the first health-associated Propionibacterium microbe: (a) comprises at least one gene encoding an ATP binding cassette transporter; (b) comprises at least one gene encoding at least one of a deoxyribose operon repressor and a type II lipase, and less than about 10% pIMPLE plasmid; or © lacks at least one gene encoding a DNA binding response regulator or a phosphoglycerate kinase.

“In some aspects, disclosed herein are pharmaceutical compositions that comprise: (a) a therapeutically effective amount of a health-associated Propionibacterium acnes microbe, wherein the health-associated Propionibacterium acnes microbe is characterized by at least one of the following: comprises at least one gene encoding at least one of a deoxyribose operon repressor and a type II lipase, and less than about 10% pIMPLE plasmid; comprises at least one gene encoding an ATP binding cassette transporter; or lacks at least one gene encoding a DNA binding response regulator or a phosphoglycerate kinase, and (b) a pharmaceutically acceptable excipient or biological stabilizer. In some embodiments, the health-associated Propionibacterium acnes microbe has been engineered or selected to comprise a deoxyribose operon repressor and a type II lipase. In some embodiments, a Cas5 protein is absent from the health-associated Propionibacterium acnes microbe. In some embodiments, the health-associated Propionibacterium acnes microbe expresses an ATP binding cassette transporter. In some embodiments, the health-associated Propionibacterium acnes microbe does not express a DNA binding response regulator or a phosphoglycerate kinase. In some embodiments, the health-associated Propionibacterium acnes microbe comprises an RT1 or RT2 ribotype. In some embodiments, the health-associated Propionibacterium acnes microbe does not comprise an RT6 ribotype. In some embodiments, the health-associated Propionibacterium acnes microbe comprises a mixture of two or more different ribotypes of Propionibacterium acnes. In some embodiments, the health-associated Propionibacterium acnes microbe comprises an HP3A11 strain, an HP3B4 strain, an HP4G1 strain, or an HP5G4 strain. In some embodiments, the pharmaceutical probiotic composition comprises an additional strain of bacteria, wherein the additional strain comprises Propionibacterium avidum or Propionibacterium granulosum. In some embodiments, the additional strain comprises Propionibacterium acnes subsp. defendens.”

There is additional summary information. Please visit full patent to read further.”

The claims supplied by the inventors are:

“1. A pharmaceutical composition comprising: a) a therapeutically effective amount of a health-associated Propionibacterium acnes microbe, wherein the health-associated Propionibacterium acnes microbe is characterized by at least one of the following: i) comprises at least one gene encoding at least one of a deoxyribose operon repressor and a type II lipase, and less than about 10% pIMPLE plasmid; ii) comprises at least one gene encoding an ATP binding cassette transporter; or iii) lacks at least one gene encoding a DNA binding response regulator or a phosphoglycerate kinase, and b) a pharmaceutically acceptable excipient or biological stabilizer.

“2. The pharmaceutical probiotic composition of claim 1, wherein the health-associated Propionibacterium acnes microbe has been engineered or selected to comprise a deoxyribose operon repressor and a type II lipase.

“3. The pharmaceutical probiotic composition of claim 1, wherein a Cas5 protein is absent from the health-associated Propionibacterium acnes microbe.

“4. The pharmaceutical probiotic composition of claim 1, wherein the health-associated Propionibacterium acnes microbe expresses an ATP binding cassette transporter.

“5. The pharmaceutical probiotic composition of claim 1, wherein the health-associated Propionibacterium acnes microbe does not express a DNA binding response regulator or a phosphoglycerate kinase.

“6. The pharmaceutical probiotic composition of claim 1, wherein the health-associated Propionibacterium acnes microbe comprises an RT1 or RT2 ribotype.

“7. The pharmaceutical probiotic composition of claim 1, wherein the health-associated Propionibacterium acnes microbe does not comprise an RT6 ribotype.

“8. The pharmaceutical probiotic composition of claim 1, wherein the health-associated Propionibacterium acnes microbe comprises less than about 1% pIMPLE plasmid.

“9. The pharmaceutical probiotic composition of claim 1, wherein the pharmaceutically acceptable excipient or biological stabilizer increases the viability of the health-associated Propionibacterium acnes microbe at a temperature from about -20° C. to about 30° C.

“10. The pharmaceutical composition of claim 1, wherein the health-associated Propionibacterium acnes microbe comprises a mixture of two or more different ribotypes of Propionibacterium acnes.

“11. The pharmaceutical probiotic composition of claim 1, wherein the health-associated Propionibacterium acnes microbe comprises an HP3A11 strain, an HP3B4 strain, an HP4G1 strain, or an HP5G4 strain.

“12. The pharmaceutical probiotic composition of claim 1, comprising an additional strain of bacteria, wherein the additional strain comprises Propionibacterium avidum, Propionibacterium acnes subsp. defendens, or Propionibacterium granulosum.

“13.-30. (canceled)”

For additional information on this patent application, see: HANZEL, David; TAYLOR, Emma. Compositions And Methods For Treatment Of Skin Disorders. Filed November 18, 2021 and posted October 13, 2022. Patent URL: https://appft.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PG01&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.html&r=1&f=G&l=50&s1=%2220220323513%22.PGNR.&OS=DN/20220323513&RS=DN/20220323513

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