COMPOSITIONS AND METHODS FOR THE TREATMENT OF ANDROGENETIC ALOPECIA

Description

1 / 57 COMPOSITIONS AND METHODS FOR THE TREATMENT OF ANDROGENETIC ALOPECIA REFERENCE TO RELATED ORDERS

[001] The application claims the benefit of the Provisional Serial Number US 63 / 457,928, filed April 7, 2023, the contents of which are incorporated by reference. BACKGROUND OF THE INVENTION

[002] Hair loss often has a negative social and psychological impact on the individual who suffers from it. Many factors are believed to contribute to hair loss, including genetics, hormones, environmental exposure, medications, psychological stress, and nutrition. One known treatment is hair transplantation, which requires anesthesia, is expensive, time-consuming, and sometimes painful. Other approaches include massage and acupuncture, but these have not proven effective. Hormones and other medications have been used to treat hair loss; however, these treatments often cause undesirable side effects, such as hair growth in unwanted areas.

[003] Consequently, there is a need for an effective therapy to stimulate hair growth. BRIEF SUMMARY OF THE INVENTION

[004] This document provides methods for treating androgenetic alopecia (AGA) in a patient who requires it. In some embodiments, the methods may include administering the compositions described in this document into the patient's skin. In some embodiments, the methods may include administering the compositions from the disclosure into the patient's skin via intradermal injection. In some embodiments, the compositions may include up to about 1% by weight of hyaluronic acid. For example, the compositions may include from about 0.2% by weight to about 0.4% by weight. Petition 870250089627, dated 02 / 10 / 2025, page 8 / 86 2 / 57 weight of hyaluronic acid. In some modalities, the compositions may be administered at least twice a week to the individual. In some modalities, the compositions may be administered approximately three times a week. In some modalities, the composition may include hyaluronic acid that is not cross-linked. In some modalities, the average molecular weight of hyaluronic acid may be up to approximately 100 kDa.

[005] In some modalities, the treatment methods of AGA may include administering the composition to the patient on consecutive days of the week. In some modalities, the compositions may be administered on three consecutive days of the week. In some modalities, the compositions may be injected to a depth of approximately 0.1 mm or more into the skin. In some modalities, the composition may be injected approximately 0.6 mm to approximately 0.8 mm deep into the skin. In some modalities, the injection area may be approximately 4 cm² or more. In some modalities, the compositions may be administered into or near a stem cell area of ​​a follicle.

[006] In some modalities, the compositions may be administered to the skin in one or more of the patient's frontotemporal scalp regions and the patient's vertex scalp region.

[007] In some modalities, treatment with the composition may improve or increase target area hair count (THAC); target area hair width (THAW); and / or hair darkening.

[008] In some embodiments, the compositions are administered to a patient who has experienced an onset of hair loss approximately three to five years prior to administration of the composition. In some embodiments, the compositions are administered to Petition 870250089627, dated 02 / 10 / 2025, page 9 / 86 3 / 57 a patient who experienced an onset of hair loss approximately ten years prior to administration of the composition. In some embodiments, the patient had previously received a hair transplant. In some embodiments, the patient received the hair transplant approximately one to two months prior to administration of the composition. In some embodiments, the patient is a male patient.

[009] In some embodiments, the compositions of the disclosure may be used to treat mild or moderate AGA. In some embodiments, the compositions of the disclosure may be used to treat a patient who has received a score of III on the Modified Norwood Hamilton Scale or a score of IV on the Modified Norwood Hamilton Scale. In some embodiments, improvement or increase in THAC, THAW and / or hair darkening is measured from about 10 days to about 160 days after administration of the composition.

[0010] In some modalities, the patient has experienced hair loss previously.

[0011] In some modalities, the compositions of the disclosure may stimulate hair growth in the frontotemporal region of the patient's scalp and / or in the vertex region of the patient's scalp.

[0012] Methods for stimulating hair growth on a patient's skin are also provided in this document. The methods may include administering the disclosure compositions to the patient's skin. In some embodiments, the compositions may be administered to the patient via intradermal injection. In some embodiments, the disclosure compositions may include up to 1% by weight of hyaluronic acid, such as about 0.2% by weight to about 0.4% by weight of hyaluronic acid. In some embodiments, the disclosure compositions may include up to 1% by weight of hyaluronic acid, such as about 0.2% by weight to about 0.4% by weight of hyaluronic acid. Petition 870250089627, dated 02 / 10 / 2025, p. 10 / 86 4 / 57 modalities, the dissemination essays can be administered at least twice a week. For example, the essays can be administered approximately three times a week. In some modalities, the composition may include hyaluronic acid that is not cross-linked. In some modalities, the average molecular weight of hyaluronic acid may be up to approximately 100 kDa.

[0013] This disclosure provides a method of administering a hair growth composition to a patient in need thereof. Methods may include administering the compositions of the disclosure into the patient's skin. In some embodiments, the compositions may be administered via intradermal injection. In some embodiments, the compositions may include up to about 1% by weight of hyaluronic acid as well as from about 0.2% by weight to about 0.4% by weight of hyaluronic acid. The composition may be administered at least twice a week, for example, about three times a week. In some embodiments, the composition may include hyaluronic acid that is not cross-linked. In some embodiments, the average molecular weight of the hyaluronic acid may be up to about 100 kDa.

[0014] In some embodiments, the methods for hair growth may involve administering the composition to the patient on consecutive days. In one embodiment, the compositions may be administered on three consecutive days per week. In some embodiments, the composition may be injected to a depth of approximately 0.1 mm or more, for example, from approximately 0.6 mm to approximately 0.8 mm deep into the skin. In some embodiments, the injection area may be approximately 4 cm2 or more. In some embodiments, the dissemination compositions may be administered into or near a stem cell area of ​​a follicle.

[0015] In some modalities, the compositions for the growth Petition 870250089627, dated 02 / 10 / 2025, page 11 / 86 5 / 57 Hair growth can be administered to the skin in one or more of the frontotemporal regions of the patient's scalp and the vertex region of the patient's scalp.

[0016] In some modalities, treatment with the composition may improve or increase target area hair count (THAC); target area hair width (THAW); and / or hair darkening.

[0017] In some embodiments, the compositions are administered to a patient who has experienced an onset of hair loss approximately three to five years prior to administration of the composition. In some embodiments, the compositions are administered to a patient who has experienced an onset of hair loss approximately ten years prior to administration of the composition. In some embodiments, the patient has previously received a hair transplant. In some embodiments, the patient received the hair transplant approximately one to two months prior to administration of the composition. In some embodiments, the patient is a male patient.

[0018] In some embodiments, the compositions may be used for hair growth in a patient who has AGA. AGA may be mild or moderate. In some embodiments, the compositions of the disclosure may be used to treat hair loss in a patient who has received a score of III on the Modified Norwood Hamilton Scale or a score of IV on the Modified Norwood Hamilton Scale. In some embodiments, improvement or increase in THAC, THAW and / or hair darkening is measured from about 10 days to about 160 days after administration of the composition. BRIEF DESCRIPTION OF THE VARIOUS VIEWS OF THE DRAWINGS

[0019] The following detailed description of the com modalities Petition 870250089627, dated 02 / 10 / 2025, p. 12 / 86 6 / 57 positions and methods for stimulating hair growth will be better understood when read in conjunction with the attached drawings. It should be understood, however, that the invention is not limited to the precise arrangements shown.

[0020] In the drawings:

[0021] Figure 1 is a drawing showing the characteristics associated with each score of the Modified Norwood-Hamilton Scale. DETAILED DESCRIPTION OF THE INVENTION I. Compositions

[0022] In some embodiments, a hair growth-stimulating composition includes hyaluronic acid. In some embodiments, the compositions described in U.S. Patent 11,337,993 may be used in this disclosure (the contents of which are incorporated herein by reference in their entirety). 1. Hyaluronic Acid (HA)

[0023] HA is a naturally occurring endogenous glycosaminoglycan. HA is found in the extracellular matrix and is widely distributed throughout the body, most abundant in the skin (~50%). HA is primarily produced by mesenchymal cells and its function in the body is to retain water; it is responsible for skin hydration and viscoelasticity; it facilitates the transport of ionic solutes and nutrients; and it protects the skin from free radical damage (Erickson & Stern, 2012).

[0024] In some embodiments, a useful composition for stimulating hair growth includes hyaluronic acid. Hyaluronic acid is a natural ligand for CD44, and has now been found to be pro-inflammatory and stimulates hair growth. Hyaluronic acid is a natural linear polymer containing repeating units of a disaccharide of e-1,4-D-glucuronic acid and e-1,3-N-acetyl-D-glucosamine, as shown in Formula (I): Petition 870250089627, dated 02 / 10 / 2025, page 13 / 86 7 / 57

[0025] The units link together to form long, linear molecules, which form random coils as they become longer. At concentrations greater than 0.1%, HA chains form a continuous network. HA can be chemically enhanced to create cross-links between HA molecules in order to adjust the physical properties of the product.

[0026] HA has been studied in a variety of medical applications, including aesthetic (i.e., dermal fillers), ophthalmic (viscoelastic), and osteoarthritis applications. Several commercial HA products are available in the US, including dermal fillers such as Juvéderm and Restylane; viscoelastic products such as Healon and NuVisc; and osteoarthritis products such as Hyalgan and Orthovisc. HA-based mesotherapy (intradermal injection of small aliquots) has been well documented in the literature as a safe treatment for skin rejuvenation. Reported adverse events associated with HA were mild and transient and included injection site pain, itching, burning, erythema, edema, petechiae, purpura, hematomas, swelling, bruising, dark circles, ecchymosis, skin scratching and pinpoint bleeding, allergic reactions, urticaria, and papule formation.The risks associated with HA dermal fillers are generally mild and transient, but rare and serious complications due to vascular occlusion have occurred, including infection, embolism, and tissue necrosis. These events are associated with deep injection of cross-linked HA products. The present invention provides hyaluronic acid. Petition 870250089627, dated 02 / 10 / 2025, page 14 / 86 8 / 57 non-crosslinked ion in phosphate-buffered saline (PBS) for use in the methods described in this document.

[0027] In some embodiments, hyaluronic acid has a low average molecular weight. In some embodiments, low average molecular weight, as used in this document, refers to ranges from about 15,000 Da to about 40,000 Da. In some embodiments, hyaluronic acid has an intermediate average molecular weight. In some embodiments, intermediate average molecular weight, as used in this document, refers to ranges from about 75,000 Da to about 350,000 Da. In some embodiments, hyaluronic acid has a high average molecular weight. In some embodiments, high average molecular weight, as used in this document, refers to about 950,000 Da and higher.

[0028] In some embodiments, hyaluronic acid has an average molecular weight ranging from about 4,000 Da or less to about 10,000 Da. In some embodiments, hyaluronic acid has an average molecular weight ranging from about 10,000 Da to about 100,000 Da. In some embodiments, hyaluronic acid has an average molecular weight ranging from about 100,000 Da to about 1,500,000 Da or higher. In some embodiments, hyaluronic acid has an average molecular weight that can be from about 40 kDa to about 100 kDa. In one embodiment, hyaluronic acid has an average molecular weight of about 60 kDa.

[0029] In some forms, hyaluronic acid has an average molecular weight between approximately 1 kDa and approximately 10 kDa, between approximately 10 kDa and approximately 50 kDa, between approximately 50 kDa and approximately 100 kDa, between approximately 100 kDa and approximately 150 kDa, between approximately 200 kDa and approximately 250 kDa, between approximately 300 kDa and approximately 350 kDa, between approximately 400 kDa and approximately 450 kDa, between approximately 500 kDa and approximately 550 kDa, between approximately 600 kDa and approximately 650 kDa, between Petition 870250089627, dated 02 / 10 / 2025, page 15 / 86 9 / 57 near 700 kDa and near 750 kDa, between near 800 kDa and near 850 kDa, between near 900 kDa and near 1,000 kDa, between near 1,000 kDa and near 1,100 kDa, between near 1,100 kDa and near 1,200 kDa, between near 1,200 kDa and near 1,300 kDa, between near 1,300 kDa and near 1,400 kDa, between near 1,400 kDa and near 1,500 kDa, between near 1 kDa and near 100 kDa, between near 100 kDa and near 250 kDa, between near 250 kDa and near 500 kDa, between near 500 kDa and near 750 kDa, between approximately 750 kDa and approximately 1000 kDa, between approximately 1000 kDa and approximately 1250 kDa, between approximately 1,250 kDa and approximately 1,500 kDa, between approximately 1 kDa and approximately 250 kDa, between approximately 1 kDa and approximately 500 kDa, between approximately 100 kDa and approximately 500 kDa, between approximately 250 kDa and approximately 750 kDa, between approximately 500 kDa and approximately 1,000 kDa, between approximately 750 kDa and approximately 1250 kDa, or between approximately 1000 kDa and approximately 1,500 kDa.

[0030] In some modalities, the average molecular weight of hyaluronic acid can be up to about 100 kDa.For example, the average molecular weight of hyaluronic acid can range from approximately 1 kDa to approximately 10 kDa, from approximately 5 kDa to approximately 15 kDa, from approximately 10 kDa to approximately 20 kDa, from approximately 15 kDa to approximately 25 kDa, from approximately 20 kDa to approximately 30 kDa, from approximately 25 kDa to approximately 35 kDa, from approximately 30 kDa to approximately 40 kDa, from approximately 35 kDa to approximately 45 kDa, from approximately 40 kDa to approximately 50 kDa, from approximately 45 kDa to approximately 55 kDa, from approximately 50 kDa to approximately 60 kDa, from approximately 55 kDa to approximately 65 kDa, from approximately 60 kDa to approximately 70 kDa, from approximately 65 kDa to approximately 75 kDa, between about 70 kDa and about 80 kDa, between about 75 kDa and about 85 kDa, between about 80 kDa and about 90 kDa, between about 85 kDa and about 95 kDa, between about 90 kDa and about 100 kDa, between about 95 kDa and about 105 kDa, in between. Petition 870250089627, dated 02 / 10 / 2025, page 16 / 86 10 / 57 near 100 kDa and near 200 kDa, between near 150 kDa and near 250 kDa, between near 200 kDa and near 300 kDa, between near 250 kDa and near 350 kDa, between near 300 kDa and near 400 kDa, between near 350 kDa and near 450 kDa, between near 400 kDa and near 500 kDa, between near 450 kDa and near 550 kDa, between near 500 kDa and near 600 kDa, between near 550 kDa and near 650 kDa, between near 600 kDa and near 700 kDa, between near 650 kDa and near 750 kDa, between near 700 kDa and near 800 kDa, between about 750 kDa and about 850 kDa, between about 800 kDa and about 900 kDa, between about 850 kDa and about 950 kDa, between about 900 kDa and about 1000 kDa, between about 950 kDa and about 1000 kDa or more.

[0031] In some embodiments, hyaluronic acid is not cross-linked. In some embodiments, hyaluronic acid is substantially free of cross-linking. In some embodiments, the composition includes free hyaluronic acid, that is, non-cross-linked hyaluronic acid. Generally, free hyaluronic acid is not exposed to cross-linking conditions. In some embodiments, the compositions may contain free hyaluronic acid, and the free hyaluronic acid may be present in concentrations between 5 and 95 percent by weight of the total hyaluronic acid.

[0032] In some forms, hyaluronic acid is cross-linked. Cross-linking can improve the lifespan of hyaluronic acid, and in some modalities, some degree of cross-linking may be desirable. In some modalities, the hyaluronic acid has sufficient cross-linking to last about a week. However, without being linked by a mechanism of action, hyaluronic acid is believed to be effective in stimulating hair growth by interacting with CD44 receptors. Therefore, in some modalities, it is desirable that the hyaluronic acid not be cross-linked so extensively that the cross-linking interferes with the hyaluronic acid's ability to interact with... Petition 870250089627, dated 02 / 10 / 2025, p. 17 / 86 11 / 57 a CD44 receiver.

[0033] The hydroxyl (--OH), carboxylic (--COOH) and / or amide (--NHCOCH.sub.3) functional groups of hyaluronic acid can be crosslinked via an ether (R--O--R), ester (R-COO--R) or carbodiimide linkage, respectively. In some embodiments, hyaluronic acid is crosslinked with 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC), glutaraldehyde (GTA), poly(ethylene glycol) diglycidyl ether (PEGDE), ethylene glycol diglycidyl ether (EGDE), divinyl sulfonate (DVS) or tetraacrylated pentaerythritol (PT).

[0034] Hyaluronic acid may have a cross-linking density of approximately 1x10⁻⁷ mol / cm³ or higher, approximately 2x10⁻⁷ mol / cm³ or higher, approximately 3x10⁻⁷ mol / cm³ or higher, approximately 4x10⁻⁷ mol / cm³ or higher, approximately 5x10⁻⁷ mol / cm³ or higher, approximately 6x10⁻⁷ mol / cm³ or higher, approximately 7x10⁻⁷ mol / cm³ or higher, approximately 8x10⁻⁷ mol / cm³ or higher, approximately 9x10⁻⁷ mol / cm³ or higher, approximately 1x10⁻⁶ mol / cm³ or higher, approximately 2x10⁻⁶ mol / cm³ or higher, approximately 3x10⁻⁶ mol / cm³ or higher, approximately 4x10⁻⁶ mol / cm³ or higher, approximately 5x10⁻⁶ mol / cm³ or higher, approximately of 6 x10-6mol / cm3 or greater, about 7 x10-6mol / cm3 or greater, about 8 x10-6mol / cm3 or greater, about 9 x10-6mol / cm3 or greater, or about 1 x10-5mol / cm3 or greater.In some forms, hyaluronic acid can have a cross-linking density between approximately 1 x 10⁻⁷ mol / cm³ and approximately 1 x 10⁻⁵ mol / cm³, between approximately 1 x 10⁻⁷ mol / cm³ and approximately 1 x 10⁻⁶ mol / cm³, between approximately 1 x 10⁻⁷ mol / cm³ and approximately 5 x 10⁻⁷ mol / cm³, between approximately 5 x 10⁻⁷ mol / cm³ and approximately 1 x 10⁻⁶ mol / cm³, between approximately 1 x 10⁻⁷ mol / cm³ and approximately 2 x 10⁻⁷ mol / cm³, between approximately 2 x 10⁻⁷ mol / cm³ and approximately 4 x 10⁻⁷ mol / cm³, between approximately 4 x 10⁻⁷ mol / cm³ and approximately 6 x 10⁻⁷ mol / cm³, between approximately 6 x 10⁻⁷ mol / cm³ and approximately 8 x 10⁻⁷ mol / cm³. x10-7mol / cm3, or between about 8 x10-7mol / cm3 and about 1 x10-6mol / cm3, between about 1. Petition 870250089627, dated 02 / 10 / 2025, p. 18 / 86 12 / 57 x10-6mol / cm3e about 1x10-5mol / cm3, between about 1 x10-6mol / cm3e about 5 x10-6mol / cm3, between about 5 x10-6 mol / cm3 and about 1x10-5mol / cm3, between about 1x10-6mol / cm3 and about 1x10-6mol / cm3 x10-6mol / cm3, between about 2 x10-7mol / cm3 and about 4 x10-7mol / cm3, between about 4 x10-7mol / cm3 and about 6 x10-7mol / cm3, between about 6 x10-7 mol / cm3 and about 8 x10-7mol / cm3, between about 8 x10-7mol / cm3 x10-7mol / cm3 and about 1x10-5mol / cm3 or between about 5 x10-7mol / cm3 and about 5 x10-6mol / cm3.

[0035] The compositions of the invention may include an amount of hyaluronic acid sufficient to provide a therapeutic effect, for example, stimulating hair growth in a patient who needs it and / or to treat Androgenetic Alopecia (AGA). In some embodiments, higher concentrations of hyaluronic acid may result in undesirable inflammation. In some embodiments, the compositions of the invention include an amount of hyaluronic acid sufficient to provide a therapeutic effect, for example, stimulating hair growth or treating AGA in a patient who needs it, and insufficient to provide an unacceptable or undesirable inflammatory response.

[0036] In some embodiments, a composition comprises about 0.001% by weight or more of hyaluronic acid, about 0.0025% by weight or more of hyaluronic acid, about 0.0050% by weight or more of hyaluronic acid, about 0.0075% by weight or more of hyaluronic acid, about 0.01% by weight or more of hyaluronic acid, about 0.025% by weight or more of hyaluronic acid, about 0.05% by weight or more of hyaluronic acid, about 0.075% by weight or more of hyaluronic acid, about 0.1% by weight or more of hyaluronic acid, about 0.25% by weight or more of hyaluronic acid, about 0.5% by weight or more of hyaluronic acid, about 0.75% by weight or more of hyaluronic acid hyaluronic acid, or about 1% Petition 870250089627, dated 02 / 10 / 2025, page 19 / 86 13 / 57 by weight or more of hyaluronic acid. In some embodiments, a composition comprises between approximately 0.001% by weight and approximately 0.0025% by weight of hyaluronic acid, between approximately 0.0025% by weight and approximately 0.005% by weight of hyaluronic acid, between approximately 0.0025% by weight and approximately 0.0075% by weight of hyaluronic acid, between approximately 0.0025% by weight and approximately 0.01% by weight of hyaluronic acid, between approximately 0.001% by weight and approximately 0.01% by weight of hyaluronic acid, between approximately 0.005% by weight and approximately 0.0075% by weight of hyaluronic acid, between approximately 0.005% by weight and approximately 0.01% by weight of hyaluronic acid, between approximately 0.0075% by weight and approximately 0.01% by weight of hyaluronic acid, between about 0.01% by weight and about 0.02% by weight of hyaluronic acid, between about 0.01% by weight and about 0.05% by weight of hyaluronic acid, between about 0.02% by weight and about 0.04% by weight of hyaluronic acid, between about 0.05% by weight and about 0.1% by weight of hyaluronic acid, between about 0.04% by weight and about 0.06% by weight of hyaluronic acid, between about 0.06% and about 0.08% by weight of hyaluronic acid, between about 0.08% by weight and about 0.1% by weight of hyaluronic acid, between about 0.1% by weight and about 0.2% by weight of hyaluronic acid, between about 0.2% by weight and about 0.3% by weight of hyaluronic acid, between about 0.1% by weight and about 0.5% by weight of hyaluronic acid, between about 0.2% by weight and about 0.4% by weight of hyaluronic acid, between about 0.5% by weight and about 1% by weight of hyaluronic acid, between about 0.3% by weight and about 0.4% by weight of hyaluronic acid, between about 0.4% by weight and about 0.5% by weight of hyaluronic acid, between about 0.5% by weight and about 0.6% by weight of hyaluronic acid, between about 0.4% by weight and about 0.6% by weight of hyaluronic acid, between about 0.6% by weight and about 0.7% by weight of hyaluronic acid, between, Petition 870250089627, dated 02 / 10 / 2025, p. 20 / 86 14 / 57 approximately 0.7% by weight and approximately 0.8% by weight of hyaluronic acid, between approximately 0.6% and approximately 0.8% by weight of hyaluronic acid, between approximately 0.8% by weight and approximately 0.9% by weight of hyaluronic acid, or approximately 0.8% by weight and approximately 1% by weight of hyaluronic acid. In some forms, a composition comprises approximately 0.1% by weight, approximately 0.11% by weight, approximately 0.12% by weight, approximately 0.13% by weight, approximately 0.14% by weight, approximately 0.15% by weight, approximately 0.16% by weight, approximately 0.17% by weight, approximately 0.18% by weight, approximately 0.19% by weight, approximately 0.2% by weight, approximately 0.21% by weight, approximately 0.22% by weight, approximately 0.23% by weight, approximately 0.24% by weight, approximately 0.25% by weight, approximately 0.26% by weight, approximately 0.27% by weight, approximately 0.28% by weight, approximately 0.29% by weight, approximately 0.3% by weight, approximately 0.31% by weight weight, approximately 0.32% by weight, approximately 0.33% by weight, approximately 0.34% by weight, approximately 0.35% by weight, approximately 0.36% by weight, approximately 0.37% by weight,approximately 0.38% by weight, approximately 0.39% by weight, approximately 0.4% by weight, approximately 0.41% by weight, approximately 0.42% by weight, approximately 0.43% by weight, approximately 0.44% by weight, approximately 0.45% by weight, approximately 0.46% by weight, approximately 0.47% by weight, approximately 0.48% by weight, approximately 0.49% by weight, approximately 0.5% by weight, approximately 0.51% by weight, approximately 0.52% by weight, approximately 0.53% by weight, approximately 0.54% by weight, approximately 0.55% by weight, approximately 0.56% by weight, approximately 0.57% by weight, approximately 0.58% by weight, approximately 0.59% by weight, approximately 0.6% by weight, approximately 0.61% by weight, approximately 0.62% by weight, approximately 0.63% by weight, approximately 0.64% by weight, approximately 0.65% by weight, approximately 0.66% by weight, approximately 0.67% by weight, approximately 0.68% by weight, approximately 0.69% by weight, approximately 0.7% by weight, approximately 0.71% by weight, approximately 0.72% by weight, approximately 0.73% by weight, approximately 0.74% by weight, approximately 0.75% by weight, approximately 0.76% by weight, Petition 870250089627, dated 02 / 10 / 2025, page 21 / 86 15 / 57 approximately 0.77% by weight, approximately 0.78% by weight, approximately 0.79% by weight, approximately 0.8% by weight, approximately 0.81% by weight, approximately 0.82% by weight, approximately 0.83% by weight, approximately 0.84% ​​by weight, approximately 0.85% by weight, approximately 0.86% by weight, approximately 0.87% by weight, approximately 0.88% by weight, approximately 0.89% by weight, approximately 0.9% by weight, approximately 0.91% by weight, approximately 0.92% by weight, approximately 0.93% by weight, approximately 0.94% by weight, approximately 0.95% by weight, approximately 0.96% by weight, approximately 0.97% by weight, approximately 0.98% by weight, approximately 0.99% by weight, approximately 1% by weight or more of hyaluronic acid.

[0037] As used throughout this description, both mcg / ml and ug / ml refer to micrograms per milliliter. In some formulations, hyaluronic acid is present in an amount of approximately 10 mcg / ml of the composition or higher, approximately 15 mcg / ml of the composition or higher, approximately 20 mcg / ml of the composition or higher, approximately 25 mcg / ml of the composition or higher, approximately 30 mcg / ml of the composition or higher, approximately 35 mcg / ml of the composition or higher, approximately 40 mcg / ml of the composition or higher, approximately 45 mcg / ml of the composition or higher, approximately 50 mcg / ml of the composition or higher, approximately 55 mcg / ml of the composition or higher, approximately 60 mcg / ml of the composition or higher, approximately 65 mcg / ml of the composition or higher, approximately 70 mcg / ml of the composition or higher, approximately 75 mcg / ml of the composition or higher, approximately 80 mcg / ml of the composition or higher. superior, approximately 85 mcg / ml of the composition or superior, approximately 90 mcg / ml of the composition or superior,approximately 95 mcg / ml of the composition or higher, approximately 100 mcg / ml of the composition or higher, approximately 110 mcg / ml of the composition or higher, approximately 120 mcg / ml of the composition or higher, approximately 130 mcg / ml of the composition or higher, approximately 140 mcg / ml of the composition or higher, approximately 150 mcg / ml of the composition, Petition 870250089627, dated 02 / 10 / 2025, p. 22 / 86 16 / 57 concentration or higher, approximately 160 mcg / ml of the composition or higher, approximately 170 mcg / ml of the composition or higher, approximately 180 mcg / ml of the composition or higher, approximately 190 mcg / ml of the composition or higher, approximately 200 mcg / ml of the composition or higher, approximately 210 mcg / ml of the composition or higher, approximately 220 mcg / ml of the composition or higher, approximately 230 mcg / ml of the composition or higher, approximately 240 mcg / ml of the composition or higher, approximately 250 mcg / ml of the composition or higher, approximately 260 mcg / ml of the composition or higher, approximately 270 mcg / ml of the composition or higher, approximately 280 mcg / ml of the composition or higher, approximately 290 mcg / ml of the composition or higher, approximately 300 mcg / ml of the composition or higher, approximately 310 mcg / ml of the composition or higher, approximately 320 mcg / ml of the composition or higher, approximately 330 mcg / ml of the composition or higher, approximately 340 mcg / ml of the composition or higher, approximately 350 mcg / ml of the composition or higher,approximately 360 mcg / ml of the composition or higher, approximately 370 mcg / ml of the composition or higher, approximately 380 mcg / ml of the composition or higher, approximately 390 mcg / ml of the composition or higher, approximately 400 mcg / ml of the composition or higher, approximately 410 mcg / ml of the composition or higher, approximately 420 mcg / ml of the composition or higher, approximately 430 mcg / ml of the composition or higher, approximately 440 mcg / ml of the composition or higher, approximately 450 mcg / ml of the composition or higher, approximately 460 mcg / ml of the composition or higher, approximately 470 mcg / ml of the composition or higher, approximately 480 mcg / ml of the composition or higher, approximately 490 mcg / ml of the composition or higher, approximately 500 mcg / ml of the composition or higher, approximately 510 mcg / ml of the composition or higher, approximately 520 mcg / ml of the composition or higher, approximately 530 mcg / ml of the composition or higher, approximately 540 mcg / ml of the composition or higher, approximately 550 mcg / ml of the composition or higher, approximately 560 mcg / ml of the composition or higher,approximately 570 mcg / ml of the composition, Petition 870250089627, dated 02 / 10 / 2025, p. 23 / 86 17 / 57 concentration or higher, approximately 580 mcg / ml of the composition or higher, approximately 590 mcg / ml of the composition or higher, approximately 600 mcg / ml of the composition or higher, approximately 610 mcg / ml of the composition or higher, approximately 620 mcg / ml of the composition or higher, approximately 630 mcg / ml of the composition or higher, approximately 640 mcg / ml of the composition or higher, approximately 650 mcg / ml of the composition or higher, approximately 660 mcg / ml of the composition or higher, approximately 670 mcg / ml of the composition or higher, approximately 680 mcg / ml of the composition or higher, approximately 700 mcg / ml of the composition or higher, approximately 710 mcg / ml of the composition or higher, approximately 720 mcg / ml of the composition or higher, approximately 730 mcg / ml of the composition or higher, approximately 740 mcg / ml of the composition or higher, approximately 750 mcg / ml of the composition or higher, approximately 760 mcg / ml of the composition or higher, approximately 770 mcg / ml of the composition or higher, approximately 780 mcg / ml of the composition or higher,approximately 790 mcg / ml of the composition or higher, approximately 800 mcg / ml of the composition or higher, approximately 810 mcg / ml of the composition or higher, approximately 820 mcg / ml of the composition or higher, approximately 830 mcg / ml of the composition or higher, approximately 840 mcg / ml of the composition or higher, approximately 850 mcg / ml of the composition or higher, approximately 860 mcg / ml of the composition or higher, approximately 870 mcg / ml of the composition or higher, approximately 880 mcg / ml of the composition or higher, approximately 890 mcg / ml of the composition or higher, approximately 900 mcg / ml of the composition or higher, approximately 910 mcg / ml of the composition or higher, approximately 920 mcg / ml of the composition or higher, approximately 930 mcg / ml of the composition or higher, approximately 940 mcg / ml of the composition or higher, approximately 950 mcg / ml of the composition or higher, approximately 960 mcg / ml of the composition or higher, approximately 970 mcg / ml of the composition, approximately 980 mcg / ml of the composition or higher.

[0038] In some modalities, hyaluronic acid is present Petition 870250089627, dated 02 / 10 / 2025, p. 24 / 86 18 / 57 in an amount in a range of about 1 mcg / ml of the composition to about 250 mcg / ml of the composition, about 10 mcg / ml of the composition to about 250 mcg / ml of the composition, about 10 mcg / ml of the composition to about 200 mcg / ml of the composition, 10 mcg / ml of the composition to about 150 mcg / ml of the composition, 10 mcg / ml of the composition to about 100 mcg / ml of the composition, about 25 mcg / ml of the composition to about 250 mcg / ml of the composition, about 25 mcg / ml of the composition to about 200 mcg / ml of the composition, about 25 mcg / ml of the composition to about 150 mcg / ml of the composition, about 25 mcg / ml of the composition to about 100 mcg / ml of the composition, approximately 50 mcg / ml of the composition to approximately 250 mcg / ml of the composition, approximately 50 mcg / ml of the composition to approximately 200 mcg / ml of the composition, approximately 50 mcg / ml of the composition to approximately 150 mcg / ml of the composition, approximately 50 mcg / ml of the composition to approximately 100 mcg / ml of the composition, approximately 75 mcg / ml of the composition to approximately 250 mcg / ml of the composition,approximately 75 mcg / ml of the composition to approximately 200 mcg / ml of the composition, approximately 75 mcg / ml of the composition to approximately 150 mcg / ml of the composition, approximately 75 mcg / ml of the composition to approximately 100 mcg / ml of the composition, approximately 100 mcg / ml of the composition to approximately 250 mcg / ml of the composition, approximately 100 mcg / ml of the composition to approximately 200 mcg / ml of the composition, approximately 100 mcg / ml of the composition to approximately 150 mcg / ml of the composition, approximately 150 mcg / ml of the composition to approximately 250 mcg / ml of the composition, approximately 200 mcg / ml of the composition to approximately 250 mcg / ml of the composition, approximately 60 mcg / ml of the composition to approximately 80 mcg / ml of the composition composition, approximately 50 mcg / ml of the composition to approximately 75 mcg / ml of the composition, approximately 25 mcg / ml of the composition to approximately 75 mcg / ml of the composition, approximately 10 mcg / ml of the composition to approximately 50 mcg / ml of the composition, or approximately 10 mcg / ml of the composition to approximately 25 mcg / ml of the composition. Petition 870250089627, dated 02 / 10 / 2025, page 25 / 86 19 / 57

[0039] In some embodiments, hyaluronic acid is present in an amount ranging from about 1 mcg / ml of the composition to about 500 mcg / ml of the composition, about 10 mcg / ml of the composition to about 500 mcg / ml of the composition, about 10 mcg / ml of the composition to about 450 mcg / ml of the composition, about 10 mcg / ml of the composition to about 400 mcg / ml of the composition, about 10 mcg / ml of the composition to about 350 mcg / ml of the composition, about 10 mcg / ml of the composition to about 300 mcg / ml of the composition, about 25 mcg / ml of the composition to about 500 mcg / ml of the composition, about 25 mcg / ml of the composition to about 450 mcg / ml of the composition, about 25 mcg / ml of the composition to approximately 400 mcg / ml of the composition, approximately 25 mcg / ml of the composition to approximately 350 mcg / ml of the composition, approximately 25 mcg / ml of the composition to approximately 300 mcg / ml of the composition, approximately 50 mcg / ml of the composition to approximately 500 mcg / ml of the composition,approximately 50 mcg / ml of the composition to approximately 450 mcg / ml of the composition, approximately 50 mcg / ml of the composition to approximately 400 mcg / ml of the composition, approximately 50 mcg / ml of the composition to approximately 350 mcg / ml of the composition, approximately 50 mcg / ml of the composition to approximately 300 mcg / ml of the composition, approximately 75 mcg / ml of the composition to approximately 500 mcg / ml of the composition, approximately 75 mcg / ml of the composition to approximately 450 mcg / ml of the composition, approximately 75 mcg / ml of the composition to approximately 400 mcg / ml of the composition, approximately 75 mcg / ml of the composition to approximately 350 mcg / ml of the composition, approximately 75 mcg / ml of the composition to approximately 300 mcg / ml of the composition, approximately 100 mcg / ml of the composition to approximately 500 mcg / ml of the composition, approximately 100 mcg / ml of the composition to approximately 450 mcg / ml of the composition, approximately 100 mcg / ml of the composition to approximately 400 mcg / ml of the composition, approximately 100 mcg / ml of the composition to approximately 350 mcg / ml of the composition, approximately 100 mcg / ml of the composition to approximately 300 mcg / ml, Petition 870250089627, dated 02 / 10 / 2025, page 26 / 86 20 / 57 of the composition, approximately 150 mcg / ml of the composition to approximately 500 mcg / ml of the composition, approximately 150 mcg / ml of the composition to approximately 450 mcg / ml of the composition, approximately 150 mcg / ml of the composition to approximately 400 mcg / ml of the composition, approximately 150 mcg / ml of the composition to approximately 350 mcg / ml of the composition, approximately 150 mcg / ml of the composition to approximately 300 mcg / ml of the composition, approximately 200 mcg / ml of the composition to approximately 500 mcg / ml of the composition, approximately 200 mcg / ml of the composition to approximately 450 mcg / ml of the composition, approximately 200 mcg / ml of the composition to approximately 400 mcg / ml of the composition, approximately 200 mcg / ml of the composition approximately 350 mcg / ml of the composition, approximately 200 mcg / ml of the composition to approximately 300 mcg / ml of the composition, or approximately 200 mcg / ml of the composition to approximately 250 mcg / ml of the composition.

[0040] In some embodiments, hyaluronic acid is present in an amount ranging from about 1 mcg / ml of the composition to about 750 mcg / ml of the composition, about 10 mcg / ml of the composition to about 750 mcg / ml of the composition, about 10 mcg / ml of the composition to about 700 mcg / ml of the composition, about 10 mcg / ml of the composition to about 650 mcg / ml of the composition, about 10 mcg / ml of the composition to about 600 mcg / ml of the composition, about 10 mcg / ml of the composition to about 550 mcg / ml of the composition, about 25 mcg / ml of the composition to about 750 mcg / ml of the composition, about 25 mcg / ml of the composition to about 700 mcg / ml of the composition, about 25 mcg / ml of the composition to approximately 650 mcg / ml of the composition, approximately 25 mcg / ml of the composition to approximately 600 mcg / ml of the composition, approximately 25 mcg / ml of the composition to approximately 550 mcg / ml of the composition, approximately 50 mcg / ml of the composition to approximately 750 mcg / ml of the composition,approximately 50 mcg / ml of the composition to approximately 700 mcg / ml of the composition, approximately 50 mcg / ml of the composition to approximately 650 mcg / ml of the composition, Petition 870250089627, dated 02 / 10 / 2025, page 27 / 86 21 / 57 approximately 50 mcg / ml of the composition to approximately 600 mcg / ml of the composition, approximately 50 mcg / ml of the composition to approximately 550 mcg / ml of the composition, approximately 75 mcg / ml of the composition to approximately 750 mcg / ml of the composition, approximately 75 mcg / ml of the composition to approximately 700 mcg / ml of the composition, approximately 75 mcg / ml of the composition to approximately 650 mcg / ml of the composition, approximately 75 mcg / ml of the composition to approximately 600 mcg / ml of the composition, approximately 75 mcg / ml of the composition to approximately 550 mcg / ml of the composition, approximately 100 mcg / ml of the composition to approximately 750 mcg / ml of the composition, approximately 100 mcg / ml of the composition to approximately 700 mcg / ml of the composition, approximately 100 mcg / ml of the composition to approximately 650 mcg / ml of the composition, approximately 100 mcg / ml of the composition to approximately 600 mcg / ml of the composition, approximately 100 mcg / ml of the composition to approximately 550 mcg / ml of the composition, approximately 150 mcg / ml of the composition to approximately 750 mcg / ml of the composition, approximately 150 mcg / ml of the composition to approximately 700 mcg / ml of the composition,approximately 150 mcg / ml of the composition to approximately 650 mcg / ml of the composition, approximately 150 mcg / ml of the composition to approximately 600 mcg / ml of the composition, approximately 150 mcg / ml of the composition to approximately 550 mcg / ml of the composition, approximately 200 mcg / ml of the composition to approximately 750 mcg / ml of the composition, approximately 200 mcg / ml of the composition to approximately 700 mcg / ml of the composition, approximately 200 mcg / ml of the composition to approximately 650 mcg / ml of the composition, approximately 200 mcg / ml of the composition to approximately 600 mcg / ml of the composition, approximately 200 mcg / ml of the composition to approximately 550 mcg / ml of the composition, approximately 300 mcg / ml of the composition to approximately 750 mcg / ml of the composition, approximately 300 mcg / ml of the composition to approximately 700 mcg / ml of the composition, approximately 300 mcg / ml of the composition to approximately 650 mcg / ml of the composition, approximately 300 mcg / ml of the composition to approximately 600 mcg / ml of the composition, approximately 300 mcg / ml of the composition to approximately 550 mcg / ml of the composition, approximately, Petition 870250089627, dated 02 / 10 / 2025, page 28 / 86 22 / 57 of 400 mcg / ml of the composition to approximately 750 mcg / ml of the composition, approximately 400 mcg / ml of the composition to approximately 700 mcg / ml of the composition, approximately 400 mcg / ml of the composition to approximately 650 mcg / ml of the composition, approximately 400 mcg / ml of the composition to approximately 600 mcg / ml of the composition, approximately 400 mcg / ml of the composition to approximately 550 mcg / ml of the composition, approximately 500 mcg / ml of the composition to approximately 750 mcg / ml of the composition, approximately 500 mcg / ml of the composition to approximately 700 mcg / ml of the composition, approximately 500 mcg / ml of the composition to approximately 650 mcg / ml of the composition, approximately 500 mcg / ml of the composition to approximately 600 mcg / ml of the composition, approximately 500 mcg / ml of the composition to approximately 550 mcg / ml of the composition, approximately 600 mcg / ml of the composition to approximately 750 mcg / ml of the composition, approximately 600 mcg / ml of the composition to approximately 700 mcg / ml of the composition, approximately 600 mcg / ml of the composition to approximately 650 mcg / ml of the composition, or approximately 700 mcg / ml of the composition to approximately 750 mcg / ml of the composition.

[0041] In some modalities, hyaluronic acid is present in an amount of approximately 100 mcg / ml, approximately 200 mcg / ml, approximately 300 mcg / ml, approximately 400 mcg / ml, approximately 500 mcg / ml, approximately 600 mcg / ml, approximately 700 mcg / ml, approximately 800 mcg / ml, approximately 900 mcg / ml, approximately 1,000 mcg / ml or more.

[0042] In some embodiments, hyaluronic acid is present in an amount ranging from about 1 mcg / ml of the composition to about 950 mcg / ml of the composition, to about 10 mcg / ml of the composition to about 950 mcg / ml of the composition, to about 10 mcg / ml of the composition to about 900 mcg / ml of the composition, to 10 mcg / ml of the composition to about 850 mcg / ml of the composition, to about 10 mcg / ml of the composition to about 800 mcg / ml of the composition, to about 25 mcg / ml of the composition to about 950 mcg / ml of the composition, to about 25 mcg / ml of the composition to about 900 mcg / ml of the composition Petition 870250089627, dated 02 / 10 / 2025, page 29 / 86 23 / 57 composition, approximately 25 mcg / ml of the composition, approximately 850 mcg / ml of the composition, approximately 25 mcg / ml of the composition, approximately 800 mcg / ml of the composition, approximately 50 mcg / ml of the composition, approximately 950 mcg / ml of the composition, approximately 50 mcg / ml of the composition, approximately 900 mcg / ml of the composition, approximately 50 mcg / ml of the composition, approximately 850 mcg / ml of the composition, approximately 50 mcg / ml of the composition, approximately 800 mcg / ml of the composition, approximately 75 mcg / ml of the composition, approximately 950 mcg / ml of the composition, approximately 75 mcg / ml of the composition, approximately 900 mcg / ml of the composition, approximately 75 mcg / ml of the composition approximately 850 mcg / ml of the composition, approximately 75 mcg / ml of the composition, approximately 800 mcg / ml of the composition, approximately 100 mcg / ml of the composition, approximately 950 mcg / ml of the composition, approximately 100 mcg / ml of the composition, approximately 900 mcg / ml of the composition, approximately 100 mcg / ml of the composition, approximately 850 mcg / ml of the composition,approximately 100 mcg / ml of the composition, approximately 800 mcg / ml of the composition, approximately 150 mcg / ml of the composition, approximately 950 mcg / ml of the composition, approximately 150 mcg / ml of the composition, approximately 900 mcg / ml of the composition, approximately 150 mcg / ml of the composition, approximately 850 mcg / ml of the composition, approximately 150 mcg / ml of the composition, approximately 800 mcg / ml of the composition, approximately 200 mcg / ml of the composition, approximately 950 mcg / ml of the composition, approximately 200 mcg / ml of the composition, approximately 900 mcg / ml of the composition, approximately 200 mcg / ml of the composition, approximately 850 mcg / ml of the composition, approximately 200 mcg / ml of the composition approximately 800 mcg / ml of the composition, approximately 300 mcg / ml of the composition, approximately 950 mcg / ml of the composition, approximately 300 mcg / ml of the composition, approximately 900 mcg / ml of the composition, approximately 300 mcg / ml of the composition, approximately 850 mcg / ml of the composition, approximately 300 mcg / ml of the composition, approximately 800 mcg / ml of the composition, approximately 400 mcg / ml of the composition Petition 870250089627, dated 02 / 10 / 2025, p. 30 / 86 24 / 57 at approximately 950 mcg / ml of the composition, at approximately 400 mcg / ml of the composition at approximately 900 mcg / ml of the composition, at approximately 400 mcg / ml of the composition at approximately 950 mcg / ml of the composition, at approximately 400 mcg / ml of the composition at approximately 900 mcg / ml of the composition, at approximately 400 mcg / ml of the composition at approximately 850 mcg / ml of the composition, at approximately 400 mcg / ml of the composition at approximately 800 mcg / ml of the composition, at approximately 500 mcg / ml of the composition at approximately 950 mcg / ml of the composition, at approximately 500 mcg / ml of the composition at approximately 900 mcg / ml of the composition, at approximately 500 mcg / ml of the composition at approximately 850 mcg / ml of the composition, approximately 500 mcg / ml of the composition, approximately 800 mcg / ml of the composition, approximately 600 mcg / ml of the composition, approximately 950 mcg / ml of the composition, approximately 600 mcg / ml of the composition, approximately 900 mcg / ml of the composition, approximately 600 mcg / ml of the composition, approximately 850 mcg / ml of the composition, approximately 600 mcg / ml of the composition, approximately 600 mcg / ml of the composition,approximately 700 mcg / ml of the composition, approximately 950 mcg / ml of the composition, approximately 700 mcg / ml of the composition, approximately 900 mcg / ml of the composition, approximately 700 mcg / ml of the composition, approximately 850 mcg / ml of the composition, approximately 700 mcg / ml of the composition, approximately 800 mcg / ml of the composition, approximately 800 mcg / ml of the composition, approximately 950 mcg / ml of the composition, approximately 800 mcg / ml of the composition, approximately 900 mcg / ml of the composition, approximately 800 mcg / ml of the composition, approximately 850 mcg / ml of the composition, approximately 950 mcg / ml of the composition, approximately 1000 mcg / ml.

[0043] In some embodiments, hyaluronic acid is present in an amount ranging from about 1 mcg / ml of composition to about 10 mcg / ml of composition. For example, hyaluronic acid is present in an amount of about 1.0 mg / ml, about 1.1 mg / ml, about 1.2 mg / ml, about 1.3 mg / ml, about 1.4 mg / ml, Petition 870250089627, dated 02 / 10 / 2025, page 31 / 86 25 / 57 approximately 1.5 mg / ml, approximately 1.6 mg / ml, approximately 1.7 mg / ml, approximately 1.8 mg / ml, approximately 1.9 mg / ml, approximately 2 mg / ml, approximately 2.1 mg / ml, approximately 2.2 mg / ml, approximately 2.3 mg / ml, approximately 2.4 mg / ml, approximately 2.5 mg / ml, approximately 2.6 mg / ml, approximately 2.7 mg / ml, approximately 2.8 mg / ml, approximately 2.9 mg / ml, approximately 3 mg / ml, approximately 3.1 mg / ml, approximately 3.2 mg / ml, approximately 3.3 mg / ml, approximately 3.4 mg / ml, approximately 3.5 mg / ml, approximately 3.6 mg / ml, approximately 3.7 mg / ml, approximately 3.8 mg / ml, approximately 3.9 mg / ml, approximately 4 mg / ml, approximately 4.1 mg / ml, approximately 4.2 mg / ml, approximately 4.3 mg / ml, approximately 4.4 mg / ml, approximately 4.5 mg / ml, approximately 4.6 mg / ml, approximately 4.7 mg / ml, approximately 4.8 mg / ml, approximately 4.9 mg / ml, approximately 5 mg / ml, about 5.5 mg / ml, about 6 mg / ml, about 6.5 mg / ml, about 7 mg / ml, about 7.5 mg / ml, about 8 mg / ml, about 8.5 mg / ml, about 9 mg / ml, about 9.5 mg / ml, about 10 mg / ml or more.

[0044] In some embodiments, a composition according to an embodiment of the invention comprises a commercially available hyaluronic acid composition. For example, suitable commercially available hyaluronic acid compositions include, but are not limited to, hyaluronic acids sold under the trademarks JUVEDERM™, RESTYLANE-L™, CAPTIQUE™, BELOTERO BALANCE™, PREVELLE SILK™, ELEVESS™, HYLAFORM™, EUFLEXXA™, GEL-ONE™, HYALGAN™, ORTHOVISC™, MONOVISC™, SUPARTZ™, SYNVISC™ and SYNVISC-ONE™.

[0045] a. Polydispersity index (PDI) of hyaluronic acid

[0046] The term polydispersity index (PD), as used in this document, characterizes in the art the width of the molecular weight distribution curve in terms of the ratio of the weight-average molecular weight Mw (which is the total weight of all polymer molecules (hyaluronic acid) in the sample divided by the total number of molecules) to the number-average molecular weight Mn (which is the molecular weight Petition 870250089627, dated 02 / 10 / 2025, page 32 / 86 26 / 57 (weighted average of each molecule multiplied by its corresponding molecular weight, i.e., the statistically weighted average molecular weight). In general, a lower PDI value indicates a narrower molecular weight distribution range.

[0047] In some embodiments, hyaluronic acid analysis can be conducted by size exclusion chromatography (SEC). In some embodiments, SEC may include separating samples, monitoring the output with a concentration detector, such as a refractometer or a UV absorbance detector, and comparing the elution time with the molar mass. In some embodiments, hyaluronic acid analysis may include the use of multi-angle light scattering devices (MALS) in series with concentration detectors. In some embodiments, the MALS instrument, a differential refractometer, and a differential viscometer with SEC may be used to study the material characteristics of hyaluronic acid. A combination of these methods may be used to determine the absolute molecular weight of hyaluronic acid, the molecular weight distribution, and radius information. 2. Carrier and Other Additives

[0048] In some embodiments, a composition includes a carrier medium. Such a carrier medium may be a biocompatible fluid suitable for injection into mammalian skin. In some embodiments, the carrier medium comprises a saline solution. In some embodiments, hyaluronic acid serves as both a carrier medium and an active ingredient.

[0049] In some embodiments, a composition includes one or more additives. Such additives may include a preservative or a biocide.

[0050] In some embodiments, a composition includes a microemulsifier, a nanoemulsifier, a solid lipid nanoparticle, a nanostructured lipid carrier, a liposome or a Petition 870250089627, dated 02 / 10 / 2025, page 33 / 86 27 / 57 gallbladder.

[0051] In some embodiments, a composition may comprise a fatty acid (e.g., oleic acid), an ester of a fatty acid and an alcohol (e.g., isopropyl myristate, isopropyl palmitate, ethyl oleate), medium-chain triglycerides, triacetin, or a terpene (e.g., limonene, metol, cinoele). In some embodiments, a composition may comprise a surfactant. For example, suitable surfactants include, but are not limited to, TWEEN™ (polysorbates), CREMOPHOR™ (mixture of macrogol glycerol hydroxystearate, PEG-40 castor oil, hydrogenated castor oil polyoxyl 40), TRANSCUTOL™ P (diethylene glycol monoethyl ether), PLUROL OLEIQUE™ (polyglyceryl-3-oleate), PLUROL ISOSTEARIQUE™ (isostearic acid ester of polyglycerols and higher oligomers) and LABRASOL™ (mixture of mono-, di- and triglycerides of C8 and C10 fatty acids and mono- and di-esters of PEG) and lecithin. In some embodiments, a composition may comprise a co-surfactant.For example, suitable co-surfactants include, but are not limited to, short- and medium-chain alcohols and polyglyceryl derivatives, including ethanol, isopropanol, isopropyl myristate, and propylene glycol.

[0052] In some embodiments, a composition comprises one or more of the following: soybean oil, jojoba oil, aloe vera oil, soybean phosphatidylcholine, water, polysorbate 80, ethanol, benzyl alcohol, isopropyl alcohol, glycerin, glyceryl monostearate, propylene glycol. II. Methods

[0053] This disclosure provides methods of treatment and administration, as well as methods of preparation of the compositions. In some embodiments, the methods described in U.S. Patent 11,337,993 may be used in this disclosure (the contents of which are incorporated herein by reference in their entirety). Petition 870250089627, dated 02 / 10 / 2025, page 34 / 86 28 / 57 1. Treatment Methods

[0054] This disclosure provides a method of treatment using the compositions described in this document. As used in this document, the terms treat, treatment or treating refer to therapeutic treatments, where the objective is to reverse, alleviate, improve, inhibit, slow down or stop the progression or severity of a disease or condition, for example, androgenetic alopecia or another form of alopecia. The term treat includes reducing or alleviating at least one adverse effect or symptom of a disease or condition, for example, androgenetic alopecia or another form of alopecia. Treatment may be considered effective if one or more symptoms are reduced, for example, the rate of hair loss is reduced. Alternatively, treatment may be considered effective if the progression of a disease is reduced or stopped.In other words, the term treatment includes not only the improvement of symptoms, but also the cessation, or at least the slowing, of the progression or worsening of symptoms compared to what would be expected in the absence of treatment. Beneficial or desired clinical outcomes include, but are not limited to, relief of one or more symptoms, reduction in the extent of the disease, stabilization (i.e., not worsening) of the disease state, delay or slowing of disease progression, improvement or palliation of the disease state, and / or remission (partial or total). For example, treatment is considered effective if the extent or amount of hair loss is reduced, the progression of hair loss is slowed or stopped, or hair growth is induced.

[0055] In some modalities, the disclosure compositions may be used to treat androgenetic alopecia (AGA). In some modalities, the disclosure compositions may improve one or more metrics associated with AGA. In some modalities, Petition 870250089627, dated 02 / 10 / 2025, p. 35 / 86 29 / 57 The compositions disclosed may be used to treat hair loss in a patient with AGA. In some forms, the compositions stimulate hair growth in a patient with AGA.

[0056] Androgenetic alopecia (AGA) is a genetically predetermined disorder due to an excessive response to androgens, characterized by the progressive loss of terminal hair on the scalp at any time after puberty and affects up to 50% of men and women. Elevated levels of androgens, including dihydrotestosterone (DHT), cause increased activation of androgen receptors in hair follicles, which causes a shortening of the anagen (growth) phase in the normal hair growth cycle. Excessive activation leads to follicular miniaturization through a progressively shorter anagen phase, resulting in thinner and shorter hair follicles. In men, hair loss is prominent in the vertex and frontotemporal regions; in women, hair loss typically occurs in the vertex region.

[0057] A method for stimulating hair growth in a patient who needs it includes administering a composition according to an embodiment of the present invention to the surface or skin of the patient. A method for administering a hair growth composition is also provided in this document.

[0058] In some embodiments, the compositions of the disclosure may be administered to the patient's skin. In some embodiments, the composition is administered topically by applying the composition to the surface of the patient's skin. In some embodiments, the composition is administered into the dermis or hypodermis of the patient's skin, for example, by injection, as described in this document. In one embodiment, the compositions may be administered to the patient's skin by intradermal injection. Petition 870250089627, dated 02 / 10 / 2025, page 36 / 86 30 / 57

[0059] The assessment of hair growth in a patient may be based on patient self-assessment, physician assessment using a standardized scale, global photograph assessment, target area hair count (THAC), target area hair width (THAW; also referred to in this document as hair diameter measurement), average hair length measurement, average hair diameter measurement, and / or hair weight measurements. In one modality, compounding may improve or increase target area hair count (THAC), THAW, average hair length, average hair diameter, hair darkening, and / or hair weight. As used in this document, target area hair count refers to the number of hairs per cm2 on a patient's head. In some modalities, higher THAC values ​​may represent better results.In some modalities, Target Area Hair Width (THAW) may refer to the cumulative width of hair in the area of ​​the patient's head being treated with the advertised compositions (the target area). Higher THAW values ​​may indicate better results.

[0060] In some respects, the composition may improve or increase the target area hair count (THAC), THAW, average hair length, average hair diameter, hair darkening, and / or hair weight by approximately 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 100%, approximately 1% to 10%, 15% to 25%, 20% to 30%, 25% to 35%, 30% to 40%, 35% to 45%, 40% to 50%, 45% to 55%, 50% to 60%, 55% to 65%, 60% to 70%, 65% to 75%, 70% to 80%, 75% to 85%, 80% to 90%, 85% to 95% or more. In some aspects, the composition may improve or increase the target area hair count (THAC), THAW, average hair length, average diameter. Petition 870250089627, dated 02 / 10 / 2025, page 37 / 86 31 / 57 of the hair, the darkening of the hair and / or weight of the hair by about 2 times, 3 times, 4 times, 5 times, 6 times, 7 times, 8 times, 9 times, 10 times, 15 times, 20 times or more.

[0061] Improvement or increase in target area hair count (THAC), THAW, average hair length, average hair diameter, hair darkening and / or hair weight can be measured at any time after treatment with the compositions of the disclosure. For example, after administration of the compositions, improvement can be measured from about 10 days to about 160 days after administration of the compound. In some modalities, improvement can be measured after approximately 10 days, approximately 20 days, approximately 30 days, approximately 40 days, approximately 50 days, approximately 60 days, approximately 70 days, approximately 80 days, approximately 90 days, approximately 100 days, approximately 110 days, approximately 120 days, approximately 130 days, approximately 140 days, approximately 150 days, approximately 160 days, approximately 170 days, approximately 180 days or more.

[0062] In some embodiments, prior to treatment with the disclosure compositions, the patient experienced hair loss for approximately 1 month, approximately 2 months, approximately 3 months, approximately 4 months, approximately 5 months, approximately 6 months, approximately 7 months, approximately 8 months, approximately 9 months, approximately 10 months, approximately 11 months, approximately 1 year, approximately 2 years, approximately 3 years, approximately 5 years, approximately 6 years, approximately 7 years, approximately 8 years, approximately 9 years, approximately 10 years, approximately or more. In some embodiments, the patient experienced hair loss for approximately three to approximately five years prior to administration of the disclosure composition.

[0063] In some modalities, the patient has received a previous hair transplant procedure. In some modalities, the patient received a hair transplant approximately 1 month to approximately 2 months ago, approximately 2 months to approximately 3 months ago, approximately 3 months to Petition 870250089627, dated 02 / 10 / 2025, p. 38 / 86 32 / 57 about 4 months, about 4 months to about 5 months, about 5 months to about 6 months, about 6 months to about 7 months, about 7 months to about 8 months, about 8 months to about 9 months, about 9 months to about 10 months, about 10 months to about 11 months, about 11 months to about 12 months or more.

[0064] In some modalities, the patient is either a male patient or a female patient.

[0065] In some modalities, the patient has mild AGA or Moderate AGA.

[0066] In some modalities, the patient received a score on the Modified Norwood Hamilton Scale of I, II, IIa, III, III vertex, IIIa, IV, V, Iva, VI, VII, or Va. The characteristics associated with each score on the Modified Norwood Hamilton Scale are presented in the figure. In some aspects, the patient received a score of III on the Modified Norwood Hamilton Scale or a score of IV on the Modified Norwood Hamilton Scale.

[0067] In some embodiments, a method for stimulating hair growth in a patient who needs it includes administering a composition according to an embodiment of the present invention to the surface or skin of the patient. In some embodiments, the composition is administered topically by applying the composition to the surface of the patient's skin. In some embodiments, the composition is administered into the dermis or hypodermis of the patient's skin, for example, by injection, as described in this document.

[0068] In some embodiments, a composition according to an embodiment of the invention is administered to a patient's skin once a day for one day, once a day for one week, once a day for one month, once a day for one year, twice a day for one day, twice a day for one year. Petition 870250089627, dated 02 / 10 / 2025, page 39 / 86 33 / 57 week, twice a day for a month, twice a day for a year, once a week for a week, once a week for a month, once a week for a year, twice a week for a week, twice a week for a month, twice a week for a year, once a month for a month, once a month for two months, once a month for six months, once a month for a year, twice a month for a month, twice a month for two months, twice a month for six months, twice a month for a year, once every two months for two months, once every two months for four months, once every two months for six months, once every two months for a year, once every three months for three months, once every three months for six months, once every three months for nine months, once every three months for a year, once every four months for four months,Once every four months for eight months, once every four months for one year, once every six months for six months, once every six months for one year, or as needed.

[0069] In some modalities, the composition is administered at least once a week, at least twice a week, at least three times a week, at least four times a week, at least five times a week, at least six times a week, at least seven times a week or more. In some modalities, the composition is administered on consecutive days of the week. In some modalities, the compositions are administered on about two consecutive days, on about three consecutive days, on about four consecutive days, on about five consecutive days, on about six consecutive days, on about seven days or more. Petition 870250089627, dated 02 / 10 / 2025, p. 40 / 86 34 / 57 In some modalities, the composition is administered on alternate days of the week. As a non-limiting example, the compositions may be administered three times a week on three consecutive days.

[0070] As a non-limiting example, the disclosure methods include administering up to 1% hyaluronic acid 3 times per week. As a non-limiting example, the disclosure methods may include administering up to 1% hyaluronic acid to the individual's skin at least 2 times per week. As a non-limiting example, the disclosure methods may include administering up to 1% hyaluronic acid to the individual's skin at least 3 times per week. As a non-limiting example, the disclosure methods may include administering up to 1% hyaluronic acid to the individual's skin at least 4 times per week. As a non-limiting example, the disclosure methods may include administering up to 1% hyaluronic acid to the individual's skin at least 5 times per week.As a non-limiting example, disclosure methods may include administering up to 1% hyaluronic acid to the individual's skin at least 6 times per week. As a non-limiting example, disclosure methods may include administering up to 1% hyaluronic acid to the individual's skin at least 7 times per week.

[0071] As a non-limiting example, the disclosure methods include administering up to 1% hyaluronic acid 3 times a week on 3 consecutive days. As a non-limiting example, the disclosure methods may include administering up to 1% hyaluronic acid to the individual's skin at least 2 times a week on two consecutive days. As a non-limiting example, the disclosure methods may include administering up to 1% hyaluronic acid to the individual's skin at least 4 times a week on two consecutive days. Petition 870250089627, dated 02 / 10 / 2025, page 41 / 86 35 / 57 mana on 4 consecutive days. As a non-limiting example, disclosure methods may include administering up to 1% hyaluronic acid to the individual's skin at least 5 times per week on 5 consecutive days. As a non-limiting example, disclosure methods may include administering up to 1% hyaluronic acid to the individual's skin at least 6 times per week on 6 consecutive days. As a non-limiting example, disclosure methods may include administering up to 1% hyaluronic acid to the individual's skin at least 7 times per week on 7 consecutive days.

[0072] As a non-limiting example, the disclosure methods may use 0.3% hyaluronic acid for intradermal injection, 3 times a week. As a non-limiting example, the disclosure methods may use 0.4% hyaluronic acid for intradermal injection, 3 times a week. As a non-limiting example, the disclosure methods may use 0.2% hyaluronic acid for intradermal injection, 3 times a week. As a non-limiting example, the disclosure methods may use 0.3% hyaluronic acid for intradermal injection, 3 times a week on three consecutive days. As a non-limiting example, the disclosure methods may use 0.4% hyaluronic acid for intradermal injection, 3 times a week on three consecutive days. As a non-limiting example, the disclosure methods may use 0.2% hyaluronic acid for intradermal injection, 3 times a week on three consecutive days. 2. Administration

[0073] A method of administering a composition according to an embodiment of the invention comprises distributing a composition according to an embodiment of the invention to a hair follicle. In some embodiments, the distribution is by administering Petition 870250089627, dated 02 / 10 / 2025, page 42 / 86 36 / 57 Topical traction, that is, applying the composition to the skin surface and allowing the composition to permeate the skin. In some embodiments, a method of administration includes a step to enhance permeation prior to topical administration of a composition. In some embodiments, delivery is by injection into the skin.

[0074] A method for administering a composition according to an embodiment of the invention comprises injecting a therapeutic amount of the composition into the skin of a patient requiring treatment. In some embodiments, a composition according to an embodiment of the invention is administered as a bolus, which, as used in this document, refers to the dosage being distributed over a time of less than ten minutes. In some embodiments, a composition according to an embodiment of the invention is administered as an infusion, which, as used in this document, refers to the dosage being distributed over a time of about ten minutes or more.

[0075] Such injection may be performed using a single needle, microneedle or similar device, or an array of needles, microneedles or similar devices. In some embodiments, a composition according to an embodiment of the invention is dispensed via a conventional syringe. In some embodiments, subdermal dispensing is performed using a hollow microneedle injector. In some embodiments, subdermal dispensing is performed with a microneedle patch that has been coated with a composition according to an embodiment of the invention, for example, which has been coated with a composition according to an embodiment of the invention by 3D printing. In some embodiments, the composition is dispensed via a jet injector. The term needle, as used in this document, refers to any device for piercing the skin and injecting a composition according to an embodiment of the invention. Petition 870250089627, dated 02 / 10 / 2025, p. 43 / 86 37 / 57 invention modality.

[0076] Preferably, the composition is administered close to the patient's hair follicle. Consequently, in some embodiments, the composition is administered by injecting a therapeutic amount of the composition into the patient's dermis (intradermal injection).

[0077] In some embodiments, the composition is administered by injecting a therapeutic amount of the composition into the patient's hypodermis. In some embodiments, the composition is administered approximately 0.4 mm to approximately 2 mm into the patient's skin (i.e., approximately 0.4 mm to approximately 3 mm from the skin surface). In some modalities, the composition is administered in doses of approximately 0.1 mm, 0.2 mm, 0.3 mm, 0.4 mm, approximately 0.5 mm, approximately 0.6 mm, approximately 0.7 mm, approximately 0.8 mm, approximately 0.9 mm, approximately 1 mm, approximately 1.1 mm, approximately 1.2 mm, approximately 1.3 mm, approximately 1.4 mm, approximately 1.5 mm, approximately 1.6 mm, approximately 1.7 mm, approximately 1.8 mm, approximately 1.9 mm, approximately 2 mm, approximately 2.1 mm, approximately 2.2 mm, approximately 2.3 mm, approximately 2.4 mm, approximately 2.5 mm, approximately 2.6 mm, approximately 2.7 mm, approximately 2.8 mm, approximately 2.9 mm, or approximately 3 mm into the patient's skin.In some forms, the composition is administered in sizes ranging from approximately 0.1 mm to approximately 0.5 mm, approximately 0.1 mm to approximately 1 mm, approximately 0.5 mm to approximately 1 mm, approximately 1 mm to approximately 1.5 mm, approximately 1.5 mm to approximately 2 mm, approximately 2 mm to approximately 2.5 mm, approximately 2.5 mm to approximately 3 mm, approximately 1 mm to approximately 3 mm, approximately 1.5 mm to approximately 3 mm, approximately 0.4 mm to approximately 0.6 mm, approximately 0.4 mm to approximately 0.8 mm, approximately 0.4 mm to approximately 1 mm, approximately 0.4 mm to approximately 1.2 mm, approximately 0.4 mm to approximately 1.4 mm, approximately 0.4 mm to approximately 1.6 mm, and approximately... 0.4mm to about 1.8mm, between about 0.4mm to about 2mm, between about 0.4mm to about 2.2mm, between about 0.4. Petition 870250089627, dated 02 / 10 / 2025, page 44 / 86 38 / 57 mm to about 2.4 mm, between about 0.4 mm and about 2.6 mm, between about 0.4 mm and about 2.8 mm, between about 0.4 mm and about 3 mm, between about 0.6 mm and about 0.8 mm, between about 0.6 mm and about 1 mm, about 0.6 mm and about 1.2 mm, between about 0.6 mm and about 1.4 mm, between about 0.6 mm and about 1.6 mm, between about 0.6 mm and about 1.8 mm, between about 0.6 mm and about 2 mm, between about 0.6 mm and about 2.2 mm, between about 0.6 mm and about 2.4 mm, between about 0.6 mm and about 2.6 mm, between about 0.6 mm and about 2.8 mm mm, between about 0.6 mm to about 3 mm, between about 0.8 mm to about 1 mm, between about 0.8 mm to about 1.2 mm, between about 0.8 mm to about 1.4 mm, between approximately 0.8 mm and approximately 1.6 mm, between approximately 0.8 mm and approximately 1.8 mm, between approximately 0.8 mm and approximately 2 mm, between approximately 0.8 mm and approximately 2.2 mm, between approximately 0.8 mm and approximately 2.4 mm, between approximately 0.8 mm and approximately 2.6 mm, between approximately 0.8 mm and approximately 2.8 mm, between approximately 0.8 mm and approximately 3 mm, between approximately 1 mm and approximately 1.2 mm, between approximately 1 mm and approximately 1.4 mm, between approximately 1 mm and approximately 1.6 mm, between approximately 1 mm and approximately 1.8 mm, between approximately 1 mm and approximately 2 mm, between approximately 1 mm and approximately 2.2 mm, between approximately 1 mm and approximately 2.4 mm, between approximately 1 mm and approximately 2.6 mm, between approximately 1 mm and approximately 2.8 mm, between approximately 1 mm and approximately 3 mm, between approximately 1.2 mm and approximately 1.4 mm, between approximately 1.2 mm and approximately 1.6 mm, between approximately 1.2 mm and approximately 1.8 mm, between approximately 1.2 mm and approximately 2 mm, between approximately 1.2 mm and approximately 2.2 mm, between approximately 1.2 mm and approximately 2.4 mm, between approximately 1.2 mm and approximately 2.6 mm, between approximately 1.2 mm and approximately 2.8 mm, between approximately 1.2 mm and approximately 3 mm, between approximately 1.4 mm and approximately 1.6 mm, between approximately 1.4 mm and approximately 1.8 mm, between approximately 1.4 mm and approximately 2 mm,between about 1.4mm to about 2.2mm, between about 1.4mm, Petition 870250089627, dated 02 / 10 / 2025, p. 45 / 86 39 / 57 to about 2.4 mm, between about 1.4 mm and about 2.6 mm, between about 1.4 mm and about 2.8 mm, between about 1.4 mm and about 3 mm, between about 1.6 mm and about 1.8 mm, between about 1.6 mm and about 2 mm, between about 1.6 mm and about 2.2 mm, between about 1.6 mm and about 2.4 mm, between about 1.6 mm and about 2.6 mm, between about 1.6 mm and about 2.8 mm, between about 1.6 mm and about 3 mm, between about 1.8 mm and about 2 mm, about 1.8 mm and about 2.2 mm, between about 1.8 mm and about 2.4 mm, between about 1.8 mm and about 2.6 mm, between about from 1.8 mm to about 2.8 mm, from about 1.8 mm to about 3 mm, from about 2.0 mm to about 2.2 mm, from about 2.0 mm to about 2.4 mm, from about 2.0 mm to about 2.6 mm, from about 2.0 mm to about 2.8 mm, from about 2.0 mm to about 3 mm, from about 2.2 mm to about 2.4 mm, from about 2.2 mm to about 2.6 mm, between approximately 2.2 mm and approximately 2.8 mm, between approximately 2.2 mm and approximately 3 mm, between approximately 2.4 mm and approximately 2.6 mm, between approximately 2.4 mm and approximately 2.8 mm, between approximately 2.4 mm and approximately mm, between approximately 2.6 mm and approximately 2.8 mm, between approximately 2.6 mm and approximately 3 mm, or between approximately 2.8 mm and approximately 3 mm in the patient's skin. In some modalities, the dissemination compositions are injected above the skull.

[0078] In one aspect, the depth of injection may vary by the thickness of the scalp in different regions of the scalp. Different regions of the scalp may have different thicknesses. For example, the average dermal thickness of the posterior scalp may be about 1443.86 μm, the thickness of the temporal scalp may be about 1349.52 μm and / or the thickness of the anterior scalp may be about 1146.13 μm. In some modalities, the depth of injection may be from about 0.7 mm to about 2 mm. Petition 870250089627, dated 02 / 10 / 2025, p. 46 / 86 40 / 57

[0079] In one embodiment, the compositions are administered into, adjacent to, or near a stem cell area of ​​the hair follicles.

[0080] In some embodiments, the injection area may be approximately 1 cm2, approximately 2 cm2, approximately 3 cm2, approximately 4 cm2, approximately 5 cm2, approximately 6 cm2, approximately 7 cm2, approximately 8 cm2, approximately 9 cm2, approximately 10 cm2, approximately 15 cm2, approximately 20 cm2, approximately 25 cm2, approximately 30 cm2, approximately 35 cm2, approximately 40 cm2, approximately 45 cm2, approximately 50 cm2, approximately 55 cm2, approximately 60 cm2, approximately cm2, approximately 70 cm2, approximately 75 cm2, approximately 80 cm2, approximately 85 cm2, approximately 90 cm2, approximately 95 cm2, approximately 100 cm2, 200 cm2, 300 cm2, 400 cm2, 500 cm2, 600 cm2, 700 cm2 or more. In one modality, the injection area may cover the entire scalp area of ​​the individual.

[0081] The compositions can be injected into a line approximately 0.2 to 0.3 cm apart. In some embodiments, the compositions can be injected into lines that are approximately 1 cm apart.

[0082] In some embodiments, a composition according to an embodiment of the invention may be administered in a plurality of injections. In some embodiments, a composition according to an embodiment of the invention is administered via about 1 injection / cm2 of skin to about 1,000 injections / cm2 of skin, about 200 injections / cm2 of skin to about 800 injections / cm2 of skin, or about 400 injections / cm2 of skin to about 650 injections / cm2 of skin. In some embodiments, a composition is administered via about 200 injections / cm2 of skin, about 250 injections / cm2 of skin, about 300 injections / cm2 of skin, about 350 injections / cm2 of skin, about 400 injections / cm2 of skin, about 450 injections / cm2 of skin, about 500 injections / cm2 of skin, about 550 Petition 870250089627, dated 02 / 10 / 2025, p. 47 / 86 41 / 57 injections / cm2 of skin, approximately 600 injections / cm2 of skin, or approximately 650 injections / cm2 of skin. The content of U.S. Patent No. 11,337,993 is incorporated herein by reference.

[0083] The compositions of the disclosure may be administered to one or more areas of the scalp. For example, the compositions may be administered to the frontal region (or central forelock), the mid-scalp (or posterior mid-scalp), the temporal scalp (sides), the vertex transition zone (or vertex transition point), and the crown (or vertex). In some embodiments, the frontal and temporal regions of the scalp may be collectively referred to as the frontotemporal region. In one embodiment, the compositions are administered to the frontotemporal regions of the scalp.

[0084] In some embodiments, topical distribution is performed after, or in conjunction with, the application of iontophoresis. For example, iontophoresis may involve the application of a mild electric current (e.g., 0.1 to 1.0 mA / cm2) to increase the cutaneous permeation of the composition. Without adhering to theory, it is believed that iontophoresis may improve skin permeation by electromigration, electroosmosis, and / or enhanced passive diffusion.

[0085] In some modalities, topical distribution is performed after, or in conjunction with, the application of electroporation. For example, electroporation may comprise the application of high-intensity, high-voltage (e.g., 50 to 1,500 V) short-duration (10 microseconds to 10 milliseconds) electrical pulses to form aqueous pores in the lipid bilayers of the stratum corneum of the skin.

[0086] In some modalities, topical distribution is performed after, or in conjunction with, the application of ultraphoresis. For example, sonophoresis may involve the application of high-frequency (e.g., approximately 500 kHz to 1250 kHz) or low-frequency acoustic waves. Petition 870250089627, dated 02 / 10 / 2025, page 48 / 86 42 / 57 frequency (for example, about 20 to about 100 kHz) or (starting with one high or low frequency and progressing to the other high or low frequency).

[0087] In some modalities, topical delivery is performed after, or in conjunction with, the application of laser ablation. Laser ablation may involve the generation of a photomechanical wave by laser ablation of a target material (e.g., polymer) placed on the skin surface.

[0088] In some modalities, topical application is performed after, or in conjunction with, magnetophoresis. Magnetophoresis may involve the application of a magnetic field, for example, pulsed electromagnetic fields, to the skin.

[0089] In some modalities, topical application is performed after radiofrequency thermal ablation. Thermal ablation may involve the application of extreme heat (e.g., approximately 300 degrees C for microseconds) to the skin surface. Without delving into theory, it is believed that thermal ablation can vaporize portions of the stratum corneum to create micron-scale channels. Thermal ablation can be performed with commercially available devices, including VIADOR™ (Syneron Medical Ltd, Israel) and PASSPORT™ (Nitto-Denko, Japan). In some modalities, thermal ablation can be performed with an erbium:yttrium-gallium-garnet (Er:YAG) laser emitting at 2,790 nm or a yttrium-scandium-gallium-garnet (YSGG) laser emitting at 2,940 nm. In some modalities, fractional laser ablation can be applied to sub-mm regions to generate points that mimic a microneedle array pattern (e.g., 40 to 300 µm with densities between 50 and 600 cm⁻¹).In some modalities, topical application is performed after the microneedling device is applied. 3. Production Methods Petition 870250089627, dated 02 / 10 / 2025, page 49 / 86 43 / 57

[0090] A process for producing a composition according to an embodiment of the invention comprises preparing an effective amount of hyaluronic acid. In some embodiments, an effective amount of hyaluronic acid may be further mixed with an effective amount of osteopontin. In some embodiments, the hyaluronic acid has an average molecular weight in a range of about 4,000 Da to 10,000 Da, in a range of about 10,000 Da to about 100,000 Da, in a range of about 15 kDa to about 50 kDa, in a range of about 75 kDa to about 350 kDa, or in a range of about 20 kDa to 1350 kDa. In some embodiments, the hyaluronic acid has an average molecular weight greater than about 950 kDa. In some formulations, an effective amount of hyaluronic acid is mixed with an effective amount of CD44-binding ligand.These processes may also include a step to prepare a physiologically acceptable carrier medium, to which the active agents are added. In some embodiments, the physiologically acceptable carrier medium is injectable.

[0091] In some embodiments, a production method includes a step for forming a microemulsion or a nanoemulsion. A microemulsion or nanoemulsion may comprise oil, water, surfactant, and co-surfactant to form a colloidal dispersion of droplet sizes in a range of about 10 nm to about 100 nm. In some embodiments, a microemulsion or nanoemulsion may comprise a fatty acid (e.g., oleic acid), an ester of a fatty acid and an alcohol (e.g., isopropyl myristate, isopropyl palmitate, ethyl oleate), medium-chain triglycerides, triacetin, or a terpene (e.g., limonene, metol, cinoele). In some embodiments, a microemulsion or nanoemulsion may comprise a surfactant. For example, suitable surfactants include, but are not limited to, TWEEN™ (polysorbates), CREPetition 870250089627, dated 10 / 02 / 2025, p. 50 / 86 44 / 57 MOPHOR™ (mixture of macrogol glycerol hydroxystearate, PEG-40 castor oil, hydrogenated castor oil polyoxyl 40), TRANSCUTOL™ P (diethylene glycol monoethyl ether), PLUROL OLEIQUE™ (polyglyceryl-3-oleate), PLUROL ISOSTEARIQUE™ (isostearic acid ester of polyglycerols and higher oligomers) and LABRASOL™ (mixture of mono-, di- and triglycerides of C8 and C10 fatty acids and mono- and di-esters of PEG) and lecithin. In some embodiments, a microemulsion or nanoemulsion may comprise a co-surfactant. For example, suitable co-surfactants include, but are not limited to, short- and medium-chain alcohols and polyglyceryl derivatives, including ethanol, isopropanol, isopropyl myristate, and propylene glycol. In some embodiments, the formation of a microemulsion or nanoemulsion involves the use of a high-pressure homogenizer, microfluidizer, and / or ultrasound.

[0092] In some embodiments, a production method includes a mixing step of a composition according to an embodiment of the invention with a solid nanoparticle. A solid nanoparticle may comprise an inorganic material, such as a metal oxide (e.g., zinc oxide, titanium dioxide) or polymers that are solid at room temperature.

[0093] In some embodiments, a production method includes a mixing step of a composition according to an embodiment of the invention with a solid lipid nanoparticle. A solid lipid nanoparticle may comprise a lipid that is solid at room temperature with a surface coating of surfactant to stabilize them as droplets with a size less than about 100 nm when dispersed in water.

[0094] In some embodiments, a production method includes a mixing step of a composition according to an embodiment of the invention with a nanostructured lipid carrier. A Petition 870250089627, dated 02 / 10 / 2025, page 51 / 86 45 / 57 nanostructured lipid carrier may comprise a fluid lipid phase embedded in a solid lipid matrix or located on the surface of solid platelets and in the surfactant layer.

[0095] In some embodiments, a production method includes a mixing step of a composition according to an embodiment of the invention with a liposome. A liposome may comprise spherical vesicles composed of amphiphilic phospholipids and cholesterol, self-assembled into multilamellar, large unilamellar and small unilamellar vesicles.

[0096] In some embodiments, a production method includes a mixing step of a composition according to an embodiment of the invention with a flexible vesicle. A flexible vesicle may comprise a material that will associate with bilayer structures, as well as components that confer flexibility. In some embodiments, a flexible vesicle comprises an ethosome (i.e., a phospholipid with a high proportion of ethanol), a niosome (i.e., nonionic surfactant), an invasome (i.e., phospholipids, ethanol, and a mixture of terpene penetration enhancer), a SECosome (i.e., surfactant, ethanol, and cholesterol), or a PEV (i.e., penetration enhancer vesicle). In some embodiments, a PEV may comprise oleic acid, limonene, or propylene glycol.

[0097] In some embodiments, a production method includes a mixing step of a composition according to an embodiment of the invention with a polymeric micelle or polymeric dendrimer. A polymeric micelle may be a colloidal carrier with a hydrophilic outer shell and a hydrophobic inner core. A polymeric micelle may be nanometric. A polymeric dendrimer may comprise a branched polymeric structure. Examples

[0098] Example 1. Evaluation of hyaluronic acid (AMP-303) in Petition 870250089627, dated 02 / 10 / 2025, page 52 / 86 46 / 57 Comparison with saline control in male subjects with androgenetic alopecia

[0099] Justification for the Study Design

[00100] Quantitative measurements of hair growth have become a standard for substantiating the efficacy of hair growth products against AGA. To date, the dosage forms typically used to treat AGA are administered topically or orally. Intradermal injections can alter the topology / contours of the skin surface, hair orientation, or other characteristics that may interfere with hair imaging or accurate serial imaging over time. To measure the impact of this route of administration on the usefulness of standard hair counts and related measurements, this study was evaluated. The study is focused on assessing what differences between pre- and post-injection may arise due to AMP-303 compared to the saline control during the study period. The local safety effects of intradermal injection of AMP-303 compared to the saline control will be collected.Furthermore, the study will include three (3) different groups of patients with androgenetic alopecia to refine the study population for future studies in androgenetic alopecia. Product and formulation of the study

[00101] The study compound is hyaluronic acid (also referred to in this document as AMP-303) for intradermal injection at a concentration of 0.3% ±0.1%.

[00102] AMP-303 for intradermal injection consists of a non-crosslinked hyaluronic acid and phosphate-buffered saline solution.

[00103] The control sterile injectable saline solution will be phosphate-buffered saline solution.

[00104] Both the AMP-303 vehicle and the saline control will be supplied as injectable solutions. Identical 1 ml syringes will be Petition 870250089627, dated 02 / 10 / 2025, page 53 / 86 47 / 57 used for AMP-303 and the control, with markings of 0.1 ml and 0.5 ml. AMP-303 and the saline control will be supplied as sterile products. Study Objectives

[00105] The aim of the study was to evaluate the safety and tolerability of AMP-303 injected into the scalp dermis compared to a saline control in male subjects with androgenetic alopecia. The study will also assess the impact (if any) of AMP-303 compared to the saline control on the methodology for assessing hair counts in male subjects with androgenetic alopecia. Furthermore, the study will be used to refine the intended population for use. Study Design

[00106] The study is a prospective, multicenter, randomized, saline-controlled, non-significant risk (NSR), early feasibility study.

[00107] The dosing regimen will include up to 2 ml of AMP-303 and saline control to be injected intradermally; the injection will occur on three consecutive days.

[00108] The study is randomized on day 0 at each investigation site. Individuals are randomly assigned to receive AMP-303 on the right or left side and saline control on the contralateral side. All individuals will receive intradermal injection of AMP-303 vehicle and saline control on days 0, 1, and 2 to the frontotemporal regions of the scalp. Individuals will receive AMP-303 on one side and saline control on the other side in the frontotemporal regions. The injection area will be approximately up to 4 cm2 and the injection volume will be up to 2 ml for each injection area. Injection will be limited to the frontotemporal regions of the scalp. Each individual is expected to be in the study for approximately 6 months (screening via Exit). Petition 870250089627, dated 02 / 10 / 2025, page 54 / 86 48 / 57

[00109] The visit schedule is as follows: Visit 1: Screening (Days -30 to -1) Visit 2: Day 0 (Injection / Baseline) Visit 3: Day 1 (Injection) Visit 4: Day 2 (Injection) Visit 5: Day 14 (±3 days) Visit 6: Day 30 (±7 days) Visit 7: Day 60 (±7 days) Visit 8: Day 90 (±7 days) Visit 9: Day 120 (±7 days) Visit 10: Day 150 (±7 days)

[00110] Approximately 36 individuals (12 individuals per group) are enrolled in this study across up to 3 research sites.

[00111] Three (3) different groups will be enrolled in the study, with approximately 12 male individuals in each group: 1) recent onset of hair loss (defined as a history of hair loss of ~3 to 5 years); 2) established hair loss (defined as a history of hair loss > 10 years); and 3) post-transplant. Group 3 will enroll individuals who have completed a hair transplant procedure that includes the bilateral frontotemporal regions. Eligible individuals must (1) be 1 to 2 months post-transplant, (2) have had a normal post-transplant healing course, and (3) have no active adverse events or medical concerns in the designated post-transplant injection areas.

[00112] On day 0, eligible individuals will be randomized to receive AMP-303 in the right or left frontotemporal region and saline control on the contralateral side (the Injection Sites). AMP-303 and saline control will be administered by a research physician via intradermal injection on a randomized basis at visits on days 0, 1, and 2. Physicians, study staff, and individuals will be blinded. Petition 870250089627, dated 02 / 10 / 2025, page 55 / 86 49 / 57 to study the product injected on each side. Individuals who are discontinued from the study will not be replaced. Potential benefits and risks

[00113] The benefits of intradermal injection of the AMP-303 Vehicle and this study include gathering safety and tolerability data for a vehicle for future investigational products, determining the effect, if any, on hair count assessments due to possible surface topology effects related to intradermal injection of the AMP-303 Vehicle and saline control, and refining the intended population for future studies. Potential risks associated with needle injection into the skin include injection site pain, erythema, hematoma, and edema. These events are expected as a result of intradermal injection of AMP-303 or saline control; however, if any particular reaction or effect is greater in severity or degree of incidence than anticipated, the occurrence may be considered an adverse event (AE). Minimizing Anticipated Risks

[00114] The risks are minimized under this protocol by: 1) Limited injection area on the scalp, consisting of no more than a total area of ​​4 cm2; 2) Low molecular weight non-crosslinked hyaluronic acid; 3) Limited to intradermal injection to a depth of approximately 0.6 mm to 0.8 mm; careful consideration of the anatomical structures of the scalp; 4) AMP-303 and saline control will be provided as a sterile product in syringes to be used for injection; 5) Injectors will be physicians experienced with intradermal injections; 6) Standard precautions with injectable materials will be followed; and / or 7) Only male subjects will be enrolled. Inclusion Criteria

[00115] The criteria for entry into the study are: Petition 870250089627, dated 02 / 10 / 2025, pp. 56 / 86 50 / 57 1. Adult males, aged 18 to 45 years at the time of consent. 2. Clinical diagnosis of mild to moderate androgenetic alopecia (AGA) in the temple and vertex region with a score of III or IV on the Modified Norwood-Hamilton Scale in individuals with approximately 3 to 5 years since the onset of hair loss, or at least 10 years since the onset of hair loss, or recent bilateral frontotemporal hair transplantation. 3. Are you willing to maintain the same hairstyle, length, and color throughout your studies? 4. Agrees to continue with the general hair care products and regimens for at least two weeks prior to Day 0 and throughout the study. 5. Are you willing to have your hair cut in the injection areas during screening and at each follow-up visit? 6. Are you willing to take photographs that could identify the individual? 7. Written informed consent before any study-related procedure. 8. Written authorization for the use and release of health and research study information. 9. Ability to follow study instructions and complete study assessment tools without assistance and with a likelihood of completing all required visits. Exclusion Criteria

[00116] The following are criteria for exclusion from participation in the study: 1. Any uncontrolled systemic disease. 2. History of a positive result for human immunodeficiency virus (HIV) or active hepatitis B or C. 3. History or current evidence of drug or alcohol abuse. Petition 870250089627, dated 02 / 10 / 2025, page 57 / 86 51 / 57 oz in the 12 months prior to the screening appointment. 4. Visible inflammatory skin disease, lesion, or scalp condition in the injection areas. 5. History of known or suspected malignancy (except non-melanoma skin cancer); treatment with chemotherapy or cytotoxic agents; or scalp radiation. 6. Any dermatological disorders of the scalp in balding and thinning areas that could interfere with the study injection or study assessments, such as fungal or bacterial infections, seborrheic dermatitis, psoriasis, eczema, folliculitis, scars, skin carcinoma, tattoos, or scalp atrophy. 7. History of or active hair loss due to any condition other than AGA, for example, but not limited to, diffuse telogen effluvium, alopecia areata, cicatricial alopecia, trichotillomania, or other genetic disorders. 8. History of significant dietary changes, weight changes, or eating disorder(s), in the researcher's opinion, that resulted in hair loss in the six months prior to the screening visit. 9. History of scalp reduction, significant trauma with related scarring, previous hair transplants (groups 1 and 2), hair extensions, and / or platelet-rich plasma (PRP) procedures on the scalp. 10. The individual used any other systemic therapy that, in the researcher's opinion, could materially affect the individual's hair growth, including, but not limited to, vitamin or homeopathic supplements for hair growth or hair health products or other steroid hormones (in any form), including anabolic steroids. 11. Any of the following preparations or procedures Petition 870250089627, dated 02 / 10 / 2025, pp. 58 / 86 52 / 57 Topical scalp changes occurring within the specified period before day 0 (baseline) weeks: Over-the-counter (OTC) topical scalp or cosmetic treatments that may affect hair growth (e.g., brands such as Aminexil, Maxilene, Nioxin, Foltene); hair growth products containing saw palmetto, copper, etc., including hair growth devices such as Cappilus, Revian, Theradome, etc.; and / or topical scalp treatments that may have ancillary effects on hair growth, including but not limited to corticosteroids, pimecrolimus, tacrolimus, and retinoids. Weeks: Topical scalp treatments for hair growth, including minoxidil, hormone therapy, antiandrogens, or other agents known to affect hair growth. Months: Laser, light source or energy treatments, or microneedling of the scalp; oral retinoids, isotretinoin. 12. Any of the following systemic medications or procedures that occur within the specified period prior to day 0 (baseline). Beta-blockers, cimetidine, diazoxide, or corticosteroids (including intramuscular and intralesional injections) within 12 weeks of Visit 2 / Baseline are permitted. Inhaled, intranasal, or ocular corticosteroids are permitted if use is stable. Stable is defined as unchanged doses and frequency for at least four weeks prior to Visit 2 / Baseline. Months: 5-alpha reductase inhibitors, such as finasteride (e.g., Propecia®) or dutasteride; retinoids, isotretinoin, vitamin A intake of approximately 10,000 IU per day, or cyclosporine therapy; and / or minoxidil. Petition 870250089627, dated 02 / 10 / 2025, p. 59 / 86 53 / 57 13. Known hypersensitivity to any component of the study products (AMP-303 vehicle or sterile saline). 14. The individual is known to be non-compliant or unlikely to comply with the requirements of the study protocol in the researcher's opinion. 15. Current enrollment in an investigational drug or device study or participation in such a study within 30 days of entry into this study. 16. A patient who has a condition or is in a situation that, in the researcher's opinion, may place the patient at significant risk, confound the study results, or significantly interfere with the patient's participation in the study. Injection administration

[00117] The injection will be limited to the frontotemporal regions of the scalp. On Day 0, individuals who qualify for the study will be randomized to receive injection (AMP-303 or saline control) in the right or left treatment areas. Standard injection site preparation will be performed (e.g., cleaned and rubbed with alcohol). The same injection technique should be used each day for each individual (days 0, 1, and 2).

[00118] Response measures:

[00119] Response measures to be evaluated include adverse events (including injection adverse events), local skin reaction: severity (none, minimal, mild, moderate, severe) of erythema, edema, hematomas will be assessed by the investigating physician and pain, itching and burning / stinging by the individual.

[00120] Vital signs, such as blood pressure, pulse, and respiratory rate, will also be measured.

[00121] Other response measures include digital image analysis of photographs of non-vertical hairs; hair counting in Petition 870250089627, dated 02 / 10 / 2025, pp. 60 / 86 54 / 57 target area (THAC); hair width in the target area (THAW); and / or hair darkening.

[00122] Standardized Photography and Digital Image Analysis (DIA)

[00123] A qualified supplier will provide instructions for taking photographs and processing digital photographs. Macro images of hair (1 cm2 target area) from a representative thinning area will be obtained to document and measure scalp hair: length, width, growth rate (anagen / telogen ratios), follicular unit ratios, and color. Digital image analysis of photographs will be used to calculate the Target Area Hair Count (THAC), the sum of Target Area Hair Widths (THAW), and hair darkening.

[00124] The modified Norwood Hamilton classification is used to classify the stages of male androgenetic alopecia (figure) and will be used to determine eligibility. Statistical Procedures

[00125] For all outcomes, descriptive statistics will be reported. Descriptive statistics will vary depending on the type of variable. In general, they will include continuous variables: descriptive statistics include number of observations, mean, median, standard deviation, minimum, maximum, and 95% confidence interval. Categorical variables will include descriptive statistics including the number in the category, the total number of observations, the percentage of individuals in each category, and the 95% confidence interval. Visits and Associated Procedures

[00126] Assessments are carried out by the same assessor throughout the study, whenever possible. Visit 1: Screening (Day -30 to -1)

[00127] The screening consultation can take place anytime from 30 days to 1 day before the initial consultation. After obtaining consent Petition 870250089627, dated 02 / 10 / 2025, pp. 61 / 86 55 / 57 informed ment, the procedures performed include inclusion / exclusion criteria; demographic data; Fitzpatrick Skin Phototype; medical history / surgical history; history of androgenetic alopecia; modified Norwood Hamilton classification; concomitant medications and simultaneous procedures; vital signs; standardized photography; review of the individual's instructions. Visit 2: Baseline and Injection (Day 0)

[00128] Screening and Day 0 may occur on the same date if no flushing of prohibited medications is required. At any time during the visit, information on changes in health status, concomitant medications, and simultaneous procedures will be collected from patients. The order of events will include inclusion / exclusion criteria (confirm eligibility); vital signs; standardized photography (completed after the above assessments); randomization; intradermal injection; local skin reaction (pre-injection and approximately 15 minutes after injection); adverse events. Visit 3: Day 1

[00129] At any time during the visit, information about adverse events, concomitant medications, and simultaneous procedures will be collected from patients. Vital signs are measured following intradermal injection; and measurement of local skin reaction (pre-injection and approximately 15 minutes after injection). Visit 4: Day 2

[00130] At any time during the visit, information about adverse events, concomitant medications, and simultaneous procedures will be collected from patients. Vital signs are measured following intradermal injection; local skin reaction (pre-injection and approximately 15 minutes after injection) is measured. Visit 5: Day 14 (±3 days)

[00131] At any time during the visit, information about Petition 870250089627, dated 02 / 10 / 2025, pp. 62 / 86 56 / 57 adverse events, concomitant medications, and simultaneous procedures will be collected from patients. Vital signs are measured followed by local skin reaction and standardized photography. Visit 6: Day 30 (±7 days)

[00132] At any time during the visit, information about adverse events, concomitant medications, and simultaneous procedures will be collected from patients. Vital signs are measured followed by local skin reaction and standardized photography. Visit 7: Day 60 (±7 days)

[00133] At any time during the visit, information about adverse events, concomitant medications, and simultaneous procedures will be collected from patients.

[00134] Vital signs are measured followed by local skin reaction and standardized photography. Visit 8: Day 90 (±7 days)

[00135] At any time during the visit, information about adverse events, concomitant medications, and simultaneous procedures will be collected from patients. Vital signs are measured followed by local skin reaction and standardized photography. Visit 9: Day 120 (±7 days)

[00136] At any time during the visit, information about adverse events, concomitant medications, and simultaneous procedures will be collected from patients.

[00137] Vital signs are measured followed by local skin reaction and standardized photography. Visit 10: Day 150 (±7 days)

[00138] At any time during the visit, information about adverse events, concomitant medications, and simultaneous procedures will be collected from patients.

[00139] Vital signs are measured followed by skin reaction. Petition 870250089627, dated 02 / 10 / 2025, pp. 63 / 86 57 / 57 local and standardized photograph. The individual is then removed from the study.

[00140] It will be recognized by those skilled in the art that changes could be made to the exemplary embodiments shown and described above without departing from the broad inventive concepts thereof. It is understood, therefore, that this invention is not limited to the exemplary embodiments shown and described, but is intended to cover modifications within the spirit and scope of the present invention, as defined by the claims. For example, specific features of the exemplary embodiments may or may not form part of the claimed invention, and various features of the disclosed embodiments may be combined. Unless specifically stated herein, the terms a, an, and the are not limited to one element but, instead, should be read as meaning at least one.

[00141] Furthermore, insofar as the methods of the present invention do not depend on the particular order of the steps set forth in this document, the particular order of the steps should not be construed as limiting the claims. Any claims directed to the methods of the present invention should not be limited to performing its steps in the order written, and one skilled in the art may easily consider that the steps may be varied and still remain within the spirit and scope of the present invention. Petition 870250089627, dated 02 / 10 / 2025, pp. 64 / 86

Claims

1 / 5 CLAIMS 1. A method for treating androgenetic alopecia (AGA) in a patient in need thereof, characterized by comprising: administering to the patient's skin a composition comprising up to about 1% by weight of hyaluronic acid at least twice a week; wherein the hyaluronic acid is not cross-linked; and wherein the hyaluronic acid comprises an average molecular weight of up to about 100 kDa; thereby treating AGA.

2. Method according to claim 1, characterized in that the composition is administered to the patient on consecutive days of the week.

3. Method according to claim 1, characterized in that the composition is administered via intradermal injection.

4. Method according to claim 3, characterized in that the composition is injected approximately 0.1 mm or more deeply into the skin.

5. Method according to claim 3, characterized in that the composition is administered to or near a stem cell area of ​​a follicle.

6. Method according to claim 1, characterized by comprising an injection area of ​​about 4 cm2 or more.

7. Method, according to claim 1, characterized in that the composition is administered to the skin comprising one or more frontotemporal regions of the patient's scalp and one vertex region of the patient's scalp.

8. Method, according to claim 1, characterized in that treatment with the composition improves or increases one or more of: a) Target area hair count (THAC); b) Target area hair width (THAW); and c) Hair darkening.

9. Method, according to claim 1, characterized in that the onset of hair loss in the patient is approximately three to five years prior to administration of the composition.

10. Method, according to claim 1, characterized in that the onset of hair loss in the patient is approximately ten years before the administration of the composition.

11. Method according to claim 1, characterized in that the patient has previously received a hair transplant.

12. Method, according to claim 11, characterized in that the patient has received the hair transplant approximately one month to approximately two months prior to the administration of the composition.

13. Method, according to claim 1, characterized in that the AGA is mild AGA or moderate AGA.

14. Method, according to claim 1, characterized in that the patient has received a score of III on the Modified Norwood-Hamilton Scale, or a score of IV on the Modified Norwood-Hamilton Scale.

15. Method, according to claim 8, characterized in that said improvement or increase is measured from about 10 days to about 160 days after administration of the composition.

16. Method, according to claim 1, characterized in that the patient has previously experienced hair loss.

17. Method, according to claim 7, characterized by hyaluronic acid stimulating hair growth in the frontotemporal region of the patient's scalp and / or in the vertex region of the patient's scalp. Petition 870250089627, dated 10 / 02 / 2025, page 66 / 86 3 / 5 18. A method for stimulating hair growth in the skin of a patient in need thereof, characterized by comprising: administering to the patient's skin a composition comprising up to about 1% by weight of hyaluronic acid at least twice a week; wherein the hyaluronic acid is not cross-linked; and wherein the hyaluronic acid comprises an average molecular weight of up to about 100 kDa, thereby stimulating hair growth in the patient's skin.

19. Method of administering a hair growth composition to a patient in need thereof, characterized by: administering to the patient's skin a composition comprising up to about 1% by weight of hyaluronic acid at least twice a week; wherein the hyaluronic acid is not cross-linked; and wherein the hyaluronic acid comprises an average molecular weight of up to about 100 kDa.

20. Method, according to claim 18 or 19, characterized in that the composition is administered to the patient on consecutive days of the week.

21. Method, according to claim 18 or 19, characterized in that the composition is administered by intradermal injection.

22. Method according to claim 21, characterized in that the composition is injected approximately 0.1 mm or more deeply into the skin.

23. The method, according to claim 21, is characterized by the composition being administered to or near a stem cell area of ​​a follicle.

24. Method according to claim 18 or 19, characterized by comprising an injection area of ​​about 4 cm2 or more.

25. Method, according to claim 18 or 19, characterized in that the composition is administered to the skin comprising one or more frontotemporal regions of the patient's scalp and one vertex region of the patient's scalp.

26. Method, according to claim 18 or 19, characterized in that the composition improves or increases one or more of: a) Target area hair count (THAC); b) Target area hair width (THAW); and c) Hair darkening.

27. Method, according to claim 18 or 19, characterized in that the onset of hair loss in the patient is approximately three to five years before administration of the composition.

28. Method, according to claim 18 or 19, characterized in that the onset of hair loss in the patient is approximately ten years before administration of the composition.

29. Method, according to claim 18 or 19, characterized in that the patient has previously received a hair transplant.

30. Method, according to claim 29, characterized in that the patient has received the hair transplant approximately one to two months prior to the administration of the composition.

31. Method, according to claim 18 or 19, characterized in that the patient suffers from androgenetic alopecia (AGA).

32. Method, according to claim 31, characterized by the AGA being mild to moderate AGA. Petition 870250089627, dated 02 / 10 / 2025, pp. 68 / 86 5 / 5 33. Method, according to claim 18 or 19, characterized in that the patient has received a score of III on the Modified Norwood-Hamilton Scale, or a score of IV on the Modified Norwood-Hamilton Scale.

34. Method, according to claim 26, characterized in that said improvement or increase is measured from about 10 days to about 160 days after administration of the composition. Petition 870250089627, dated 02 / 10 / 2025, p. 69 / 86

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