Prophylactic protection against viral infections

Inventors

Squiquera, LuisHodge, ThomasSulley, Jamie

Assignees

Orgenesis Inc

Publication Number

US-11331378-B2

Publication Date

2022-05-17

Expiration Date

2037-04-28

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Abstract

The present disclosure provides methods for prophylactically treating a subject for viral infections comprising topically administering a ranpirnase composition. The disclosure also provides compositions that could be used for prophylactic treatment.

Core Innovation

The invention provides methods for prophylactically treating a subject to protect against sexually-transmitted viral infections by topically administering compositions comprising ribonucleases. The compositions may be in various forms such as gels, creams, ointments, lotions, solutions, suspensions, or sprays, and include pharmaceutically acceptable excipients. The disclosed ribonucleases include members of the ribonuclease A superfamily such as ranpirnase, its '805 variant, Amphinase 2, and recombinant Amphinase 2.

The problem addressed is the significant public health threat posed by sexually transmitted infections like HIV. Current prophylactic measures rely on mechanical barriers such as condoms or oral antiretroviral drugs, which have drawbacks including inconsistent use, reduced effectiveness due to poor compliance, interference from other medications, and side effects like nausea and diarrhea. There is a need for prophylactic measures that are easy to use and free from such side effects.

This invention offers antiviral prophylactic measures that do not require injection or oral administration, instead using topical application of ribonuclease-based compositions before or during sexual intercourse. The compositions may use personal lubricants as vehicles to deliver and stabilize the ribonuclease, and the ribonuclease concentration may range from about 0.01% to 10% by weight or from about 6 μg/ml to about 66 μg/ml. The treatment thereby increases resistance to sexually-transmitted viral infections, including HIV, HPV, HSV, hepatitis B and C, and cytomegalovirus.

Claims Coverage

The patent contains one independent claim with multiple inventive features that define a method for increasing resistance to sexually-transmitted viral infection using topical application of ribonuclease compositions.

Topical prophylactic treatment using unconjugated ribonuclease at effective concentration

A method comprising topically applying a composition comprising an unconjugated ribonuclease at a concentration of 6 μg/ml or greater to increase resistance to HIV infection compared with untreated subjects.

Use of ribonuclease A superfamily members as active agents

The method employs ribonucleases selected from the ribonuclease A superfamily, including ranpirnase, its '805 variant, Amphinase 2, and recombinant Amphinase 2.

Versatile pharmaceutical forms and personal lubricant compositions

The composition for topical application can be formulated as a personal lubricant or as gel, cream, ointment, lotion, solution, suspension, or spray, facilitating ease of use and application to body regions exposed to sexually-transmitted viruses.

Specific pharmaceutically acceptable excipients in compositions

The compositions may contain excipients such as glycerin, hydroxyethylcellulose, chlorhexidine gluconate, gluconolactone, methylparaben, sodium hydroxide, propylene glycol, sorbitol, benzoic acid, among others for stability and performance enhancement.

Ribonuclease concentration range in compositions

The ribonuclease is present in an amount from about 0.01% to about 10% by weight in the composition, including narrower ranges such as 0.1% to 1%, or specific amounts like about 1%, 5%, or 10%.

Timing and frequency of topical application

The composition is applied topically prior to or during sexual intercourse and can be applied one to five times per day to maintain prophylactic efficacy.

Targeted topical administration sites

The topical application can be directed to body regions exposed to sexually-transmitted viruses, including vaginal, extra-vaginal, intra-vaginal, anal, peri-anal, and intra-anal sites.

The claims define a method that provides prophylactic protection against HIV and other sexually-transmitted viral infections by topical administration of ribonuclease-containing compositions formulated with specific excipients, applied at effective concentrations and frequencies to exposed body areas.

Stated Advantages

The prophylactic treatment does not require injection or oral administration, avoiding associated side effects like nausea and diarrhea.

Topical application is easy to use and may improve user compliance over mechanical barriers or oral prophylactics.

Compositions incorporating ribonucleases provide effective antiviral protection without cytotoxicity at effective concentrations.

The invention allows flexibility in formulation forms, including personal lubricants, enhancing acceptability and practicality for users.

Documented Applications

Prophylactic treatment to prevent sexually-transmitted viral infections including HIV, HPV, herpes simplex viruses, hepatitis B and C viruses, and cytomegalovirus through topical application.

Application of ribonuclease-containing compositions prior to or during sexual intercourse.

Use of personal lubricants containing ribonucleases for antiviral protection.

Intravaginal rings impregnated with ranpirnase to provide sustained prophylactic release against viral infections.

Administration of modified bacteria (e.g., transfected E. coli or Lactobacillus) producing ribonucleases at mucosal surfaces for prophylactic protection of tissues such as vagina, rectum, digestive tract, or external genitalia.

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