DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Status of the Claims
Claims 1-3 and 6-13 are pending. Claims 1 and 7-13 were amended and claim 14 was canceled in the response filed April 20, 2026.
Claims 6-10 remain withdrawn from further prosecution for the reasons made of record.
Terminal Disclaimer
The terminal disclaimer filed on September 18, 2023, disclaiming the terminal portion of any patent granted on this application which would extend beyond the expiration date of Application No. 18/116,849 has been reviewed and is accepted. The terminal disclaimer has been recorded.
Claim Interpretation
Legal standard: Broadest Reasonable Interpretation (BRI):
“treatment of chronic pain using transdermal hormone supplementation”: Treating chronic pain using transdermal hormone supplementation is an intended use recitation. The claimed composition must be capable of treating chronic pain using transdermal hormone supplementation. However, the composition is not limited to this or any particular use. The composition as claimed can be used in other applications so long as the composition is also capable of treating chronic pain using transdermal hormone supplementation. Prior art that reads on the claims does not have to recognize treating chronic pain so long as the prior art composition is capable of doing so.
“an amount of L-DOPA sufficient to raise HGH levels in a human”: Sufficient to raise HGH levels in a human is an intended use recitation. The claimed composition must be capable of raising HGH levels in a human. However, the composition is not limited to this or any particular use. The composition as claimed can be used in other applications so long as the composition is also capable of raising HGH levels in a human. Prior art that reads on the claims does not have to recognize raising HGH levels in a human so long as the prior art composition is capable of doing so.
“aqueous gel”: The specification does not define, nor exemplify, “aqueous gel” or “gel”, accordingly under BRI, the “plain meaning” of this term at the filing date, consistent with the specification controls.
The term "aqueous gel" broadly refers to an aqueous dispersion, in semi-solid form comprising water and a hydrophilic polymeric substance dispersed therein. See, e.g., Bar-Shalom et al (WO 2015/177288A1) at p. 6. See also generally, Saroha et al. (Int’l J. Pharm., Chem. And Biol. Sciences 3 :495-503 (2013)).
“the L-DOPA has a molecular weight of approximately 197 g/mo(l)”: “L-DOPA” is limited to the single structure on page 4, line 26 of the specification
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, the molecular weight of which is 197.188 g/mol.
“wherein eucalyptol and menthol are included in concentrations effective to both alleviate localized pain and enhance passive transdermal delivery of the hormone supplement component”: Alleviate localized pain and enhance passive transdermal delivery are intended use recitations. The claimed composition must be capable of alleviating localized pain and enhancing passive transdermal delivery. However, the composition is not limited to this or any particular use. The composition as claimed can be used in other applications so long as the composition is also capable of alleviating localized pain and enhancing passive transdermal delivery. Prior art that reads on the claims does not have to recognize alleviating localized pain and enhancing passive transdermal delivery so long as the prior art composition is capable of doing so.
“is configured to enable coordinated systemic and local treatment of chronic pain through co-delivery of L-DOPA and the simultaneous localized delivery of analgesic agents”: Enabling coordinated systemic and local treatment of chronic pain is an intended use recitations. The claimed composition must be capable of enabling coordinated systemic and local treatment of chronic pain. However, the composition is not limited to this or any particular use. The composition as claimed can be used in other applications so long as the composition is also capable of enabling coordinated systemic and local treatment of chronic pain. Prior art that reads on the claims does not have to recognize enabling coordinated systemic and local treatment of chronic pain so long as the prior art composition is capable of doing so.
Claim Rejections - 35 USC § 112(a) - withdrawn
The rejections of claims 1-3 and 11-14 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, for new matter, written description, and enablement are withdrawn in view of the amendment filed April 20, 2026.
Claim Rejections - 35 USC § 112(b) - withdrawn
The rejection of claims 11-14 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, is withdrawn in view of the amendment filed April 20, 2026.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 1-3 and 11-13 are rejected under 35 U.S.C. 101 because the claimed invention is directed to natural phenomenon without significantly more. Claims 1-3 and 11-14 recite a naturally occurring product, which is not markedly different from its naturally occurring counterpart. See MPEP §§ 2106 et seq. This rejection has been modified to address the amendment to the claims filed January 21, 2025.
Claims 1-3 and 11-13 are directed to a composition for the treatment of chronic pain using transdermal hormone supplementation delivered as an aqueous gel comprising a hormone supplement component comprising an amount of L-DOPA sufficient to raise HGH levels in a human, wherein the L-DOPA has a molecular weight of approximately 197 g/mol, and an analgesic component comprising a therapeutically effective mixture of β-caryophyllene, eucalyptol, CBD, and menthol. The CBD is present at approximately 1% by weight of the aqueous gel. The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception for the following reasons. This judicial exception is not integrated into a practical application because the claimed composition comprises naturally occurring components. The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception because for the following reasons.
Step 1: Is the claim to a process, machine, manufacture or composition of matter? The instant claims are directed to a statutory patent-eligible subject matter category, a composition of matter.
Step 2a Prong 1: Is the claim directed to a law of nature, a natural phenomenon (Product of nature), or an abstract idea? The claims are directed to a nature-based product: an aqueous gel comprising a combination of a hormone supplement comprising L-DOPA, and an analgesic component comprising β-caryophyllene, eucalyptol, CBD, and menthol. The closest naturally-occurring counterpart is the individual nature-based components of the combination. This approach is supported by MPEP § 2106.04(c)(II)(A): “Because there is no counterpart mixture in nature, the closest counterparts to the claimed mixture are the individual components of the mixture, i.e., each naturally occurring species by itself. See, e.g., Funk Bros., 333 U.S. at 130, 76 USPQ at 281”
As evidenced by Soares et al. (Plant signaling and behavior 9:4, pp. 1-8 (2014)- previously cited), L-DOPA is a naturally occurring plant product. Plants produce hundreds of non-protein amino acids, among which L-DOPA, a compound with strong allelopathic activity, stands out. This allelochemical is found in large quantities (1% and 4–7% in the leaves and seeds, respectively) in velvet bean [Mucuna pruriens (L.) var. utiliz], a legume of the Fabaceae family that has a nutritional quality comparable to the soybean (p. 2). L-DOPA has also been found at high levels in fava bean (Vicia faba L.), one of the oldest crops in Europe, traditionally used for animal feed and human food, and as broad beans for direct human consumption. Id. See also the as-filed application at para. [0173]. The chemical structure of the L-DOPA is the same in nature and in the composition. The specification describes L-DOPA as a treatment for Parkinson’s disease in paragraph [0016].
As evidenced by Delgado-Povedano et al. (Tatlanta 208: 120384, pp. 1-10 (2020)- previously cited), Cannabis sativa extracts contain cannabidiol ((CBD; pp. 2, 5, 8), β-caryophyllene (pp. 4 and 6), eucalyptol (pp. 5 and 7), and menthol (pp. 5 and 7). Examiner further notes that the as-filed application indicates that β-caryophyllene, eucalyptol, CBD, and menthol are naturally found within Cannabis. See specification at e.g., paras. [0048]-[0052], [0069]-[0070], [0129] and [0154]. The chemical structures of CBD, β -caryophyllene, eucalyptol, and menthol are the same in nature and in the composition. The functional properties of CBD, β -caryophyllene, eucalyptol, and menthol are the same in nature and in the composition: the specification asserts that CBD can be used for chronic pain (para. [0174]), that the combination of CBD and β-caryophyllene can be used for chronic pain (para. [0071]), that β-caryophyllene has antinociceptive properties, blocking sensory neuron detection of pain stimuli (para. [0072]), that menthol exhibits analgesic properties and is used topically to treat inflammatory pain (para. [0129]), and that eucalyptol relieves pain (para. [0153]).
An “aqueous gel” may also be naturally occurring. For instance, but not limited to, aloe vera pulp or gel can read on a naturally occurring aqueous gel.
There is no evidence in the claims, specification, or prior art that the aqueous gel comprising combination of L-DOPA, β-caryophyllene, eucalyptol, CBD, and menthol is markedly different from the corresponding elements in nature. Although the amended claims recite an intended use of treatment for chronic pain and coordinated systemic and local treatment of chronic pain, there is no evidence in the specification or art that the combination of L-DOPA, β-caryophyllene, eucalyptol, CBD, and menthol as a whole possesses this activity in a way that is different than the L-DOPA, β-caryophyllene, eucalyptol, CBD, and menthol on their own in nature. The specification acknowledges that all other elements of the combination possess the ability to treat pain on their own and are not transformed by being in the combination. There is no evidence for any structural or functional differences between the claimed nature-based product and the closest naturally-occurring counterpart. Therefore, the claims are directed to a natural phenomenon.
Step 2a Prong 2: Does the claim recite additional elements that integrate the judicial exception into a practical application? The claims recite the intended use “treatment of chronic pain using transdermal hormone supplementation,” “sufficient to raise HGH levels in a human,” “therapeutically effective amounts,” “effective to both alleviate localized pain and enhance passive transdermal delivery,” and “to enable coordinated systemic and local treatment of chronic pain”. Under BRI the amount of the L-DOPA, β-caryophyllene, eucalyptol, CBD, and menthol in the aqueous gel must be capable of treating chronic pain using transdermal hormone supplementation. However, the composition is not limited to these or any particular use. The composition as claimed can be used in other applications as long as the composition is also capable of the claimed intended use. As a result, the claimed judicial exception is not integrated into a practical application.
Step 2b: Does the claim recite additional elements that amount to significantly more than the judicial exception? The claims recite the intended use “treatment of chronic pain using transdermal hormone supplementation,” sufficient to raise HGH levels in a human,” and “therapeutically effective amounts,” “effective to both alleviate localized pain and enhance passive transdermal delivery,” and “to enable coordinated systemic and local treatment of chronic pain”. Under BRI the amount of the L-DOPA, β-caryophyllene, eucalyptol, CBD, and menthol in the aqueous gel must be capable of treating chronic pain using transdermal hormone supplementation. However, the composition is not limited to this or any particular use. The composition as claimed can be used in other applications as long as the composition is also capable of the claimed intended use. As a result, the claims, as a whole, do not recite any additional elements that amount to significantly more than the judicial exception.
Claim 1 is therefore patent ineligible.
Regarding claim 2, as noted in the as-filed specification at paras. [0174] and [0176], salicylic glycosides, e.g., salicin is an active ingredient of willow bark. Thus, salicylic glycosides are naturally occurring plant products. There is no evidence that the addition of the salicylic glycosides renders the composition markedly different in structure, function or any way from the naturally-occurring counterpart. This judicial exception is not integrated into a practical application because only a composition comprising naturally occurring components is claimed. Claim 2 does not recite any elements that amount to anything significantly more than the judicial exception. Although the claims recite the intended use “treatment of chronic pain using transdermal hormone supplementation” and “therapeutically effective amounts” the compositions of matter are not limited to this or any particular use. Therefore, claim 2 is ineligible.
Regarding claim 3, as noted in the as-filed specification at paras. [0150] and [0175], 2,5-dimethoxy-p-cymene is a phytochemical naturally found in the essential oils of plants within the family Asteraceae, such as Arnica montana. There is no evidence that the addition of the 2,5-dimethoxy-p-cymene renders the composition markedly different in structure, function or any way from the naturally-occurring counterpart. This judicial exception is not integrated into a practical application because only a composition comprising naturally occurring components is claimed. Claim 3 does not recite any elements that amount to anything significantly more than the judicial exception. Although the claims recite the intended use “treatment of chronic pain using transdermal hormone supplementation” and “therapeutically effective amounts” the compositions of matter are not limited to this or any particular use. Therefore, claim 3 is ineligible.
With respect to claim 11, as evidenced by Soares et al. (Plant signaling and behavior 9:4, pp. 1-8 (2014)- previously cited), L-DOPA is a naturally occurring plant product found in large quantities (1% and 4–7% in the leaves and seeds, respectively) in velvet bean [Mucuna pruriens (L.) var. utiliz], a legume of the Fabaceae family that has a nutritional quality comparable to the soybean (p. 2). The amount of L-DOPA recited in the claims does not render the claimed composition markedly different that the naturally occurring counterpart, integrate the judicial exception into a practical application, or provide significantly more than the judicial exception. Therefore, claim 11 is patent ineligible.
With respect to claim 12, the as-filed application indicates that eucalyptol oil and CBD are naturally found within Cannabis. See specification at e.g., paras. [0048]-[0052], [0069]-[0070], [0129] and [0154]. The amount of eucalyptol oil and CBD recited in the claims does not render the claimed composition markedly different that the naturally occurring counterpart, integrate the judicial exception into a practical application, or provide significantly more than the judicial exception. Therefore, claim 12 is patent ineligible.
With respect to claim 13, the as-filed application indicates that menthol is found in peppermint oil (Mentha piperaeatheroleum). See specification at e.g., paras. [0127], [0171]. The amount of peppermint oil recited in the claim does not render the claimed composition markedly different that the naturally occurring counterpart, integrate the judicial exception into a practical application, or provide significantly more than the judicial exception. Therefore, claim 13 is patent ineligible.
Response to Applicant’s Arguments
Applicant's arguments filed April 20, 2026, have been fully considered but they are not persuasive.
Applicant argues that the claimed composition is not a product of nature but rather a “specific, multi-component formulation that does not exist in nature in any single natural source.” Reply 7. This argument is not persuasive. Individual nature-based components of the claimed combination are an appropriate naturally-occurring counterpart (MPEP 2106.04(c)(II)(A)).
According to Applicant the Office action’s reliance on Funk Bros. is misplaced because the specification discloses a synergistic effect, which is “a markedly different functional characteristic not present in the individual components in nature. Reply 8. Applicant points to paragraphs [0171] and [0172] of the original specification for support. This argument is not persuasive because Applicant’s argument is unsupported by evidence. The section of the original specification referenced by Applicant describes synergy as a characteristic of the claimed composition but does not provide any evidence that synergy occurs. There is no reduction to practice or experimental data presented anywhere in the specification.
Applicant argues that the Office action’s assertion that aqueous gel includes naturally-occurring gels “ignores that the claimed aqueous gel is a manufactured formulation comprising specific components, not a naturally occurring plant.” Reply 8. This argument is not persuasive. The rejection does not argue that the claimed formulation is a plant but rather that aqueous gels are nature-based products. The claim term “aqueous gel” is generic and includes nature-based embodiments such as aloe vera.
Applicant argues that dependent claims 11-13 recite specific concentration ranges “that reflect deliberate human formulation choices”. Applicant argues that these concentration ranges are not found in nature. Reply 8. This argument is not persuasive. First, patentability is based on the properties of the claimed product itself, not on how the product is made, including whether human choices were made. Second, there is no evidence that the claimed concentrations render the nature-based products markedly different than the counterparts in nature.
Applicant argues that the claims integrate the judicial exception into a practical application do more than link natural products to a field of use because “L-DOPA provides systemic hormone supplementation while the analgesic components (b-caryophyllene, eucalyptol, CBD, menthol) simultaneously provide localized pain relief at the site of application.” Reply 9. In addition, Applicant argues that “eucalyptol and menthol serve a dual role as both analgesic agents and penetration enhancers for the L-DOPA”. Reply 9. This argument is not persuasive. Each of these components contributes its own individual function to the combination. There is no evidence in the specification or anywhere on record that the combination of L-DOPA, β-caryophyllene, eucalyptol, CBD, and menthol as a whole possesses a structure, function, or other property that is different than the L-DOPA, β-caryophyllene, eucalyptol, CBD, and menthol on their own in nature. In contrast, as evidenced by the cited art and description in the specification, L-DOPA on its own provides systemic hormone supplementation, b-caryophyllene, eucalyptol, CBD, and menthol on their own provide local analgesia, and eucalyptol and menthol on their own modulate the cell membrane in a way that enhances penetration.
Applicant argues that the claims do not preempt all uses of a natural phenomenon because they “are limited to a particular multi-component aqueous gel formulation with specific functional requirements for coordinated systemic and local treatment, which is a human-engineered solution.” Reply 9. This argument is not persuasive. Because the limitations pertaining to treatment of chronic pain, hormone supplementation, and penetration enhancement do not actually provide a treatment or prophylaxis, e.g., it is merely an intended use of the claimed invention or a field of use limitation, then it cannot integrate a judicial exception under the "treatment or prophylaxis" consideration (See MPEP § 2106.04(d)(2)).
Applicant argues that the claims recite significantly more than the judicial exception because “[the] specific combination of L-DOPA with b-caryophyllene, eucalyptol, CBD, and menthol in an aqueous gel, where eucalyptol and menthol serve as both analgesic agents and synergistic penetration enhancers for the hormone supplement component, represents a nonconventional arrangement of components.” Reply 10. Further, Applicant argues that “the synergistic results of the claimed composition in the present application would not have been expected from the individual components alone.” Reply 10. This argument is not persuasive. As stated above, there is no evidence in the specification or anywhere on record that the combination of L-DOPA, β-caryophyllene, eucalyptol, CBD, and menthol as a whole possesses a structure, function, or other property that is different than the L-DOPA, β-caryophyllene, eucalyptol, CBD, and menthol on their own in nature. In contrast, L-DOPA on its own provides systemic hormone supplementation, b-caryophyllene, eucalyptol, CBD, and menthol on their own provide local analgesia, and eucalyptol and menthol on their own modulate the cell membrane in a way that enhances penetration. Furthermore, as stated above, Applicant’s assertion of synergy and unexpected results is not supported by evidence.
For these reasons, the rejection is maintained.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under pre-AIA 35 U.S.C. 103(a) are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 1 and 11-13 are rejected under 35 U.S.C. 103 as being unpatentable over Fitzsimmons et al. (WO 2020/257538), as evidenced by Levodopa (ChemSpider ID 5824, accessed 7/26/2023 at URL chemspider.com/Chemical-Structure.5824.html- previously cited), in view of King (accessed at URL cannabisplace.com.au/learn/parkisons-and-cbd/, pp. 1-8 (2020), previously cited, hereinafter referred to as “King PD”), Delgado-Povedano et al. (Tatlanta 208: 120384, pp. 1-10 (2020), previously cited), Ligouri (U.S. 2022/0105107, previously cited), Bundrla et al, “A Review on Natural Permeation Enhancer for Transdermal Drug Delivery System and Permeation Evaluation,” Int'l J Pharm Pharma Res. Human 19: 56-72 (2020) (previously cited PTO-892 10/26/2023), Vaay, “Menthol to limonene: a cool guide to CBD gel ingredients,” accessed at URL uk.vaay.com/blogs/cbd-magazine/ cbd-gel-ingredients, pp. 1-11 (2021) (previously cited PTO-892 10/26/2023), Saroha et al., “Transdermal Gels-An Alternative Vehicle for Drug Delivery” Int'l J. Pharm., Chem. And Biol. Sciences 3 :495-503 ( 2013) (previously cited PTO-892 10/26/2023), L-DOPA, “L-DOPA for Growth Hormone’ ; Supplements in Review (2016) accessed at URL supplementsinreview.com/- growth-hormone, I-dopa ..., pp. 1-6 (previously cited PTO-892 10/26/2023), Sudo et al. (“Transdermal absorption of L-dopa from hydrogel in rats,” European Journal of Pharmaceutical Sciences, 7 (1998) 67-71), Nerenberg (US 20050143343), Quay (US 20050031549), Tsuk (US 4,933,184), Zupan (US 4,440,777), Scandiffio et al. (“Protective Effects of (E)-β-Caryophyllene (BCP) in Chronic Inflammation,” Nutrients. 2020 Oct 26;12(11):3273), Vu et al. (US 20180344663), Mosbaugh et al. (US 20080038219), Giniger et al. (US 20070122362), and Theobold et al. (US 20070026054 A1).
Determining the scope and contents of the prior art.
Fitzsimmons et al. teach transdermal delivery formulations comprising a cannabidiol, with or without one or more additional active agents through the dermis of a subject, wherein the formulation comprises a) a transdermal delivery formulation in an amount less than about 60 %w/w, comprising i. one or more phosphatides and ii. one or more fatty acids; b) water in an amount less than about 50% w/w, a Cannabidiol with or within one or more additional active agents (abstract, claim 1, 3, 7-9, 52). Additional active agents in the transdermal formulations include levodopa (para. [0095], claim 60). Transdermal formulations comprising levodopa can be used to treat Parkinson’s disease (para. [0087], [0095], claims 52 and 60). Fitzsimmons et al. teach that an effective amount of CBD and additional active agents is sufficient to achieve the alleviation or amelioration of the signs, symptoms, or causes of a disease (para. [0017], [0052]-[0055]). Fitzsimmons exemplify compositions containing 2.5 % wt CBD (Tables 6-7). The compositions can be formulated as a gel containing water (paras. [0070], [0074], [0115], [0177]). Fitzsimmons et al. teach that the transdermal delivery formulations can comprise menthol as a skin penetration enhancer (e.g., paras. [0082], [0176], [0250], claim 41). Menthol can be also be incorporated for cooling pain relief in an amount from about 0.1% w/w to about 1.0% w/w (para. [00102], [00176]) or 0.05 to 5% w/w (claim 41).
The teaching of Fitzsimmons et al. maps to claim 1 as follows:
Claim 1
Primary Reference
A composition for treatment of chronic pain
Fitzsimmons teaches that the transdermal formulations containing CBD and additional active agents can be used for the treatment of multiple diseases including pain, severe pain, chronic neuropathic pain, and Parkinson’s disease (para. [0087], claim 53). In Example 4, Fitzsimmons reduce to practice the treatment of a patient suffering from severe pain (para. [00296]): “A male patient, age 43 presents with severe pain in his back that requires the patient to take oxycontin on a regular basis. The patient’s doctor determines that the patient is at risk of becoming addicted to oxycontin and prescribes a transdermal delivery formulation containing CBD at a concentration of 75mg/kg applied daily to the back of the patient. Within a few days following application of the transdermal delivery formulation containing CBD, the patient begins to suffer from a reduction of the pain in his back. Over the next few weeks, the amount of pain the patient suffers was reduced by over 50%. The patient continues to apply the transdermal formulation containing CBD to his back with the result that the patient is able to maintain his pain with Tylenol and/or ibuprofen.”
using transdermal
Fitzsimmons is entirely directed to transdermal formulations of CBD and additional active agents (entire document, especially claims 1-61 and Examples 3-4).
Fitzsimmons teach (para. [0008]): “disclosed herein is a transdermal delivery formulation of an active agent through the dermis of a patient, including the skin, nail or hair follicle, wherein the formulation comprises a) a transdermal delivery formulation in an amount less than about 60% w/w, comprising i. one or more phosphatides and ii. one or more fatty acids; b) water in an amount less than about 50% w/w and Cannabidiol.”
In Example 3, Fitzsimmons reduced to practice the plasma pharmacokinetic (PK) profile of test article cannabidiol (CBD) following the administration of a single topical dose to CD-1 mice. Animals in each group received topical administration of either 2.5% or 5% CBD using a 1 ml syringe to draw up exactly 100 µl. Compound was applied in the shaved area only.
In Example 4, Fitzsimmons reduced to practice transdermal administration of CBD to treat chronic severe pain: “ Within a few days following application of the transdermal delivery formulation containing CBD, the patient begins to suffer from a reduction of the pain in his back.”
hormone supplementation
delivered as an aqueous gel
Fitzsimmons teaches that the transdermal formulation is aqueous (i.e. water-containing formulations) (para. [0035]): “In an embodiment, a transdermal delivery formulation contains water in a concentration of at least 0.1%, at least 0.2%, at least 0.3%, at least 0.4%, at least 0.5%, at least 1%, at least 2%, at least 3%, at least 4%, at least 5%, at least 10%, at least 15%, at least 20%, at least 25%, at least 30%, at least 35%, at least 40%, at least 45%, at least 50%, at least 55%, at least 60%, at least 65%, at least 70% or more w/w of the transdermal delivery formulation.”
The transdermal delivery formulation shown in Table 3 contains 59.65% deionized water.
Fitzsimmons also teaches that the transdermal formulation is a gel, including an aqueous gel (para. [0066], [0069], [0074], [0075]). See especially para [0069]: “the performance of a transdermal delivery formulation is further improved by including a nonionic detergent and polar gelling agent or including a powdered surfactant. In both aqueous and anhydrous forms of the composition, detergents, typically nonionic detergents are added. In general, the nonionic detergent should be present in an amount between about 1% w/w to 30% w/w of a transdermal delivery formulation. Typically, in the compositions wherein a transdermal delivery formulation is topped off with a polar or aqueous solution containing detergent, the amount of detergent is relatively low - e.g., 2-25% w/w, or 5-15% w/w or 7-12% w/w of a transdermal delivery formulation. However, in compositions that are essentially anhydrous and are topped-off by powdered detergent, relatively higher percentages are usually used - e.g., 20-60% w/w.”
See especially para [0074]: “ In the presence of a polar gelling agent, such as water, glycerol, ethylene glycol or formamide, a micellular structure is also often achieved. Typically, the polar agent is in molar excess of the nonionic detergent. The inclusion of the nonionic detergent/polar gelling agent combination results in a more viscous and cream-like or gel-like formulation which is suitable for application directly to the skin. This is typical of the aqueous forms of the composition.”
comprising a hormone supplement component comprising an amount of L-DOPA sufficient to raise HGH levels in a human
wherein the L-DOPA comprises C9H11NO4 with a molecular weight of approximately 197 g/mol
Fitzsimmons teaches that the transdermal formulations containing CBD and an additional active agent may contain L-DOPA1 as the additional agent (para. [0095]):
“In an embodiment, the transdermal delivery formulation comprises cannabidiol and an additional active agent for the treatment of Parkinson’s disease, including one or more of the following, Benztropine mesylate, Entacapone, Dopar, Larodopa, Levodopa and carbidopa, Pramipexole, Rasagiline, Ropinirole HCl, Rotigotine, Safinamide, Tasmar or Trihexphenidyl.”
Fitzsimmons reduces to practice the treatment of Parkinson’s disease in para. [00298]: “A male patient 56 years of age presents with Parkinson’s disease. The patient has begun to lose motor function and mental cognition. The doctor prescribes a transdermal formulation with CBD, starting at 20 mg/kg and increasing every two weeks until reaching 75mg/kg. Within a short period of time following administration of the transdermal formulation with CBD, the severity of the symptoms of Parkinson’s disease begin to ameliorate and the onset of new symptoms is slowed.”
comprising an analgesic component comprising a therapeutically effective amount of
Fitzsimmons teaches in para. [0017] that the agents of the transdermal formulation are present in “an effective amount” which means: “the amount of the defined component sufficient to achieve the desired chemical composition or the desired biological and/or therapeutic result… the desired result is the alleviation or amelioration of the signs, symptoms, or causes of a disease, or any other desired alteration of a biological system. When the desired result is a therapeutic response, the effective amount will, without limitation, vary depending upon the specific disease or symptom to be treated or alleviated, the age, gender and weight of the subject to be treated, the dosing regimen of the formulation, the severity of the disease condition, the manner of administration and the like, all of which can be determined readily by one of skill in the art.”
b-caryophyllene
eucalyptol
cannabidiol (CBD), present at approximately 1% by weight of the aqueous gel, and
Fitzsimmons teach generally in para. [0052] that the effective amount of CBD in a transdermal formulation is: “10 mg/kg, 15 mg/kg, 20 mg/kg, 25 mg/kg, 30 mg/kg, 35 mg/kg, 40 mg/kg, 50 mg/kg, 55 mg/kg, 60 mg/kg, 65 mg/kg, 70 mg/kg, 75 mg/kg, 80 mg/kg, 85 mg/kg, 90 mg/kg, 95 mg/kg, 100 mg/kg, 105 mg/kg, 110 mg/kg, 115 mg/kg, 120 mg/kg, 125 mg/kg, 130 mg/kg, 135 mg/kg, 140 mg/kg, 145 mg/kg, 150 mg/kg, 155 mg/kg, 160 mg/kg, 165 mg/kg, 170 mg/kg, 175 mg/kg, 180 mg/kg, 190 mg/kg, 195 mg/kg, 200 mg/kg, 205 mg/kg, 210 mg/kg, 215 mg/kg, 220 mg/kg, 225 mg/kg, 230 mg/kg, 235 mg/kg, 240 mg/kg, 245 mg/kg, 250 mg/kg, 275 mg/kg, 300 mg/kg, 325 mg/kg, 350 mg/kg, 375 mg/kg, 400 mg/kg, 425 mg/kg, 450 mg/kg, 475 mg/kg or greater than 500 mg/kg.”
In Example 4, Fitzsimmons reduce to practice the treatment of a patient suffering from severe pain (para. [00296]). Therefore, the amount of CBD in the transdermal formulation taught by Fitzsimmons is an effective amount to treat chronic pain and to achieve an analgesic effect: “A male patient, age 43 presents with severe pain in his back that requires the patient to take oxycontin on a regular basis. The patient’s doctor determines that the patient is at risk of becoming addicted to oxycontin and prescribes a transdermal delivery formulation containing CBD at a concentration of 75mg/kg applied daily to the back of the patient. Within a few days following application of the transdermal delivery formulation containing CBD, the patient begins to suffer from a reduction of the pain in his back. Over the next few weeks, the amount of pain the patient suffers was reduced by over 50%. The patient continues to apply the transdermal formulation containing CBD to his back with the result that the patient is able to maintain his pain with Tylenol and/or ibuprofen.”
menthol
Fitzsimmons teaches that the transdermal formulations containing CBD and an additional active agent may contain menthol as the additional agent (para. [0102]), [0176], [0250], claim 41). See especially para. [0176]: “Menthol, phenol, and terpenoids, e.g., camphor, can be incorporated for cooling pain relief. For example, menthol may be included in an amount ranging from about 0.1% w/w to about 1.0% w/w.” See especially claim 41 and para. [0250]): “the formulation comprises menthol in an amount between about 0.05-5 %w/w of the formulation.” Therefore, the amount of menthol in the transdermal formulation taught by Fitzsimmons is an effective amount to treat chronic pain and to achieve an analgesic effect.
wherein eucalyptol and menthol are included in concentrations effective to both alleviate localized pain and enhance passive transdermal delivery of the hormone supplement component without the use of microneedles, iontophoresis, or electroporation
Fitzsimmons teaches that the transdermal formulations include permeation enhancers, such as menthol, and that the transdermal formulations can be administered passively.
Regarding permeation enhancement, Fitzsimmons teaches in para. [0024]: “For transdermal topical administration in particular for agents other than buffer, a suitable formulation typically involves a penetrant that enhances penetration of the skin and is, in some embodiments, composed of chemical permeation enhancers (CPEs).”
In addition, Fitzsimmons teaches in para. [0063]: “A transdermal delivery formulation comprises mixtures wherein the components interact synergistically and induce skin permeation enhancements better than that induced by the individual components. Synergies between chemicals can be exploited to design potent permeation enhancers that overcome the efficacy limitations of single enhancers. Several embodiments disclosed herein utilize one or more distinct permeation enhancers.”
In addition, Fitzsimmons teaches in para. [0064: “For topical administration, and in particular transdermal administration, a transdermal delivery formulation will comprise penetrants including either or both chemical penetrants (CPEs) and peptide-based cellular penetrating agents (CPPs) that encourage transmission across the dermis and/or across membranes including cell membranes, as would be the case in particular for administration by suppository or intranasal administration, but for transdermal administration as well.”
Regarding menthol functioning as an analgesic and permeation enhancer, Fitzsimmons teaches in para.
[0082] that menthol has a documented “capability for effecting skin penetration” in addition to its effect of cooling pain relief.
Regarding passive administration (i.e. without the use of microneedles, iontophoresis, or electroporation), Fitzsimmons teaches in para. [0167]: “a transdermal delivery formulation itself is simply placed on the skin and spread across the surface and/or massaged to aid in penetration. The amount of transdermal delivery formulation used is typically sufficient to cover a desired surface area. In some embodiments, a protective cover is placed over the formulation once it is applied and left in place for a suitable amount of time, i.e., 5 minutes, 10 minutes, 20 minutes or more; in some embodiments an hour or two. The protective cover can simply be a bandage including a bandage supplied with a cover that is impermeable to moisture. This essentially locks in the contact of a transdermal delivery formulation to the skin and prevents distortion of a transdermal delivery formulation by evaporation in some cases. The composition may be applied to the skin using standard procedures for application such as a brush, a syringe, a gauze pad, a dropper, or any convenient applicator.”
wherein the components of the aqueous gel act synergistically are configured to enable coordinated systemic and local treatment of chronic pain through co-delivery of L-DOPA and the simultaneous localized delivery of analgesic agents
Fitzsimmons teaches in para. [0057]: “A transdermal delivery formulation comprise mixtures wherein the components interact synergistically and induce skin permeation enhancements better than that induced by the individual components. Synergies between chemicals can be exploited to design potent permeation enhancers that overcome the efficacy limitations of single enhancers. Several embodiments disclosed herein utilize three to five distinct permeation enhancers.”
Ascertaining the differences between the prior art and the claims at issue.
1) Fitzsimmons teaches that L-DOPA is one of several additional agents that may be combined with CBD in the transdermal formulation but does not reduce this embodiment to practice.
2) Fitzsimmons does not explicitly teach hormone supplementation, or an amount of L-DOPA sufficient to raise HGH levels in a human.
3) Fitzsimmons does not teach that the transdermal formulation contains b-caryophyllene.
4) Fitzsimmons does not teach that the transdermal formulation contains eucalyptol.
5) Fitzsimmons teaches that menthol is one of several analgesic and permeation enhancers in the transdermal formulation with CBD but does not reduce this embodiment to practice.
See claim map above.
Resolving the level of ordinary skill in the pertinent art.
1) It is within the ordinary level of skill in the art to treat Parkinson’s disease with L-DOPA and the combination of L-DOPA and CBD is known
King PD teaches that levodopa (i.e. L-DOPA2) is the most common treatment of Parkinson’s disease. Levodopa side effects include muscle stiffness, tremors, anxiety, and confusion. King PD teaches that CBD oil can be effective at counteracting these side effects of levodopa (p. 5). King PD teaches that CBD has been scientifically shown to treat the adverse effects that Parkinson’s causes to the brain, including the decrease of dopaminergic neurons that affect people with Parkinson’s. CBD has further been shown to reverse the adverse effects on the cannabinoid system caused by Parkinson’s, e.g., pain and tremors (pp. 2-3).
Sudo et al. (Section 1) and Theobold et al. (¶ [0014]) corroborate that L-Dopa is a known therapeutic agent used for Parkinson’s.
2) It is within the ordinary level of skill in the art to administer L-DOPA by a transdermal route
Sudo et al. teach the development of transdermal delivery system for L-dopa in the treatment of Parkinson’s disease. Sudo et al. corroborate that L-Dopa is a therapeutic agent used for Parkinson’s. Sudo et al. teach that transdermal administration of this drug is superior to oral and intravenous routes because Parkinson’s disease patient cannot comply with oral administration and sometimes pull out needles for injection (Section 1).
Theobald et al. teach transdermal pharmaceutical preparations containing L-DOPA for the treatment of Parkinson’s disease (¶ [0014]). Theobald et al. teach that the concentration of active agent may be 0.1 to 50%-wt., preferably 1 to 10%-wt (¶ [0048]).
3) It is within the ordinary level of skill in the art to raise HGH levels by administering L-DOPA
The prior art teaches that L-DOPA is known to raise HGH levels in a human. Supplements in Review teaches that L-DOPA stimulates growth hormone release (p. 1). This effect is corroborated by Nerenberg which teaches in para. [0055]: “L-Dopa is converted to dopamine in the body and acts on the brain to increase the release of human growth hormone”. See also Quay et al. para. [0040].
4) It is within the ordinary level of skill in the art to use CBD in hormone supplementation
Ligouri teaches a transdermal composition, for self-administering bioidentical hormone replacement and hormone balancing therapy and hormone balancing comprising Cannabidiol (CBD) in various forms including nano-emulsified [reads on aqueous gel] configurations (abstract). The compositions, which are topically applied by the user are transdermally or topically delivered to the vascular system of the user in accordance with a dosage protocol established that will optimize the hormone levels of the use. Id. The compositions can be administered as hormone replacement therapy (e.g., paras. [0003], [0004], [0009]-[0013], claim 16). Ligouri teach that the CBD can be in the form of broad-spectrum full spectrum, and isolate forms of cannabidiol (CBD) (para. [0002], [0011], [0022], claim 1). Full spectrum form of CBD provides firstly, a back-up support: Many terpenes and phenolic have effects similar to those of CBD on mood, pain and inflammation (para. [0022]). Further, full-spectrum CBD emits the property of bioavailability; CBD alone might not absorb or travel as far through the body without its entourage. A few of the terpenoids found in cannabis extracts are so good at moving drugs across skin barriers that they are added to products designed for transdermal delivery. In addition, the full-spectrum form of CBD enhances metabolism. Id. Ligouri teaches that the compositions can be used to treat pain (e.g., para. [0005], [0022], [0026]-[0028], claim 16).
5) It is within the ordinary level of skill in the art to administer Cannabis extracts which are known to contain β-caryophyllene, which has known therapeutic effects on pain and Parkinson’s
Fitzsimmons et al. teach that the CBD can be administered as a full-plant CBD-dominant hemp extract oil (para. [0002]). As evidenced by King, full-spectrum oil include all cannabis compounds, acids, and terpenes. This is the most natural form of medicinal cannabis oil as a once its extracted from the plant; the chemical compounds are not manipulated. CBD broad-spectrum is a combination of the CBD isolate and CBD full-spectrum oil except for the presence of THC (pp. 5-6).
Delgado-Povedano et al. teach that Cannabis extracts contain cannabidiol (CBD; pp. 2, 5, 8), β-caryophyllene (pp. 4 and 6), eucalyptol (pp. 5 and 7), and menthol (pp. 5 and 7).
Scandiffio et al. teaches that (E)-b-caryophyllene (BCP) is widely distributed in the plant kingdom and has therapeutic potential in chronic inflammation (abstract). Scandiffio et al. teaches that BCP can be used to treat pain (Section 4.3, page 13): “ In neuropathic pain models, BCP reduced spinal neuroinflammation and the oral administration was more effective than the subcutaneously injected synthetic CB2 agonist JWH-133. Thus, BCP may be highly effective in the treatment of long-lasting, debilitating pain states.” Scandiffio et al. also teaches that BCP can be used to treat Parkinson’s disease (Section 4.3, page 14): “Parkinson’s disease (PD) is a long-term neurodegenerative disorder characterized by progressive dopaminergic neurons loss in the substantia nigra pars compacta (SNc). Treatment of mice with BCP rescued dopaminergic neurons and decreased microglia and astrocyte activation, as evidenced by reduced levels of Iba-1 and glial fibrillary acidic protein (GFAP) expression. BCP, in addition to attenuation of pro-inflammatory cytokines and inflammatory mediators such as COX-2 and iNOS, also restored antioxidant enzymes and inhibited lipid peroxidation as well as glutathione depletion. BCP acts via multiple neuroprotective mechanisms in murine models, thus it may be viewed as a potential treatment and/or preventative agent for Parkinson’s disease.”
6) It is within the ordinary level of skill in the art to use eucalyptol and menthol as permeation enhancers in transdermal delivery
Bundrla et al. review the various permeation enhancers that can be used to accelerate permeation of drug across the skin for development of transdermal delivery systems (abstract). Bundrla et al. teach at p. 68: “Menthol is one of the potent penetration enhancers… Eucalyptol is a cyclic ether and a monoterpenoid known by several synonyms such as 1,8-cineole… 1,8-cineale has also been used for the percutaneous absorption of several lipophilic drugs through the hairless mouse.” The prior art review of Saroha et al. corroborates that menthol and eucalyptol are known permeation enhancers for transdermal administration (p. 499, col. 2).
See also Tsuk, entire document and claims is directed to the use of menthol as a transdermal drug permeation enhancer.
See also Zupan, entire document and claims is directed to the use of eucalyptol as a transdermal drug permeation enhancer.
Sudo et al. teach that transdermal penetration of L-dopa was enhanced by menthol in vitro and in vivo (Section 4).
7) It is within the ordinary level of skill in the art to use eucalyptol and menthol as analgesics
Vaay teaches a CBD gel to treat chronic muscle pain that combines CBD with menthol. Vaay teaches that the CBD is an active ingredient for pain (p. 4). In addition, Vaay teach that the menthol alleviates physical symptoms of pain with its “soothing, cooling sensation” (p. 8).
Vu et al. teach cannabis based therapeutic products for chronic pain further comprising menthol (para. [0141]) and eucalyptol (para. [0163]) as analgesics.
Giniger et al. teaches that both menthol and eucalyptol have analgesic properties (para. [0044], [0045], [0051]). See also Mosbaugh et al. para. [0069]-[0070].
Considering objective evidence present in the application indicating obviousness or nonobviousness.
The specification does not include any objective evidence or reduction to practice that suggests an unexpected result.
Obviousness rationale combining prior art elements according to known methods to yield predictable results (MPEP § 2143.01(A))
It would have been obvious to one of ordinary skill in the art at the time the invention was filed to 1) select L-dopa as the additional active agent combined with CBD in the transdermal formulation taught by Fitzsimmons, 2) to further add b-caryophyllene to the CBD – L-dopa transdermal formulation taught by Fitzsimmons, 3) to further add eucalyptol to the CBD – L-dopa transdermal formulation taught by Fitzsimmons, and 4) to select menthol as an analgesic and for permeation enhancement to the CBD – L-dopa transdermal formulation taught by Fitzsimmons. The rationale for obviousness is combining prior art elements according to known methods to yield predictable results (MPEP § 2143.01(A)). The relevant findings for this rationale are as follows.
(1) The prior art included each element claimed, although not necessarily in a single prior art reference, with the only difference between the claimed invention and the prior art being the lack of actual combination of the elements in a single prior art reference. In the instant case, the only chemical and/or structural differences between the claimed invention and the primary reference of Fitzsimmons is 1) the selection of L-dopa as the additional active agent combined with CBD, 2) the further addition of b-caryophyllene, 3) the further addition of eucalyptol, and 4) the selection of menthol as an analgesic and for permeation enhancement in the CBD transdermal formulation taught by Fitzsimmons. These differences are found in the prior art: 1) Fitzsimmons, King PD, Sudo et al., and Theobold et al. each teach L-dopa for treating Parkinson’s disease; 2) Delgado-Povedano et al. and Scandiffio et al. teach b-caryophyllene for treating pain and Parkinson’s disease; 3) Bundrla et al., Zupan, Vu et al., Giniger et al., Mosbaugh et al., and Saroha et al. each teach eucalyptol for treating pain and/or as a permeation enhancer; and 4) Fitzsimmons, Bundrla et al., Tsuk, Sudo et al., Vu et al., Giniger et al., Saroha et al., and Mosbaugh et al. each teach menthol for treating pain and/or as a permeation enhancer. Therefore, the only difference between the claimed invention and the prior art is the actual combination of elements in a single prior art reference.
(2) One of ordinary skill in the art could have combined the elements as claimed by known methods, and that in combination, each element merely performs the same function as it does separately. 1) One of ordinary skill in the art could have selected the L-dopa taught by Fitzsimmons, King PD, and Sudo et al. as the additional active ingredient in the transdermal CBD formulation for Parkinson’s disease treatment taught by Fitzsimmons using the known method of incorporating L-dopa in a transdermal formulation taught by Fitzsimmons, Sudo et al., and Theobold et al. One of ordinary skill in the art would expect that the L-dopa performs the function of treating Parkinson’s disease in the combination, which is the same function it performs separate from the combination, as taught by Fitzsimmons, King PD, Sudo et al., and Theobold et al. In addition, King PD teach the combination of L-dopa and CBD for Parkinson’s disease, including in the treatment of pain. 2) One of ordinary skill in the art could have added the b-caryophyllene taught by Delgado-Povedano et al. and Scandiffio et al. to the transdermal CBD formulation for Parkinson’s disease treatment taught by Fitzsimmons using the known method of incorporating full-plant CBD-dominant hemp extract oil taught by Fitzsimmons, which contains β-caryophyllene according to Delgado-Povedano et al. One of ordinary skill in the art would expect that β-caryophyllene performs the function of treating pain and Parkinson’s disease in the combination, as evidenced by Scandiffio et al. which is the same function it performs separate from the combination. 3) One of ordinary skill in the art could have added the eucalyptol taught by Bundrla et al., Zupan, Vu et al., Giniger et al., Saroha et al., and Mosbaugh et al. to the transdermal CBD formulation for Parkinson’s disease treatment taught by Fitzsimmons using the known method of incorporating permeation enhancers and analgesics taught by Fitzsimmons. One of ordinary skill in the art would expect that eucalyptol performs the function of treating pain, as evidenced by Vu et al., Giniger et al., and Mosbaugh et al., and enhancing permeation, as evidenced by Bundrla et al., Saroha et al., and Zupan, which is the same function it performs separate from the combination. 4) One of ordinary skill in the art could have added the menthol taught by Fitzsimmons, Bundrla et al., Tsuk, Sudo et al., Vaay, Vu et al., Giniger et al., Saroha et al., and Mosbaugh et al. to the transdermal CBD formulation for Parkinson’s disease treatment taught by Fitzsimmons using the known method of incorporating permeation enhancers and analgesics taught by Fitzsimmons. One of ordinary skill in the art would expect that menthol performs the function of treating pain, as evidenced by Vaay, Vu et al., Giniger et al., Mosbaugh et al. and Fitzsimmons, and enhancing permeation, as evidenced by Bundrla et al., Tsuk, Sudo et al., Saroha et al., and Fitzsimmons, which is the same function it performs separate from the combination. Therefore, one of ordinary skill in the art could have combined the elements as claimed by known methods, and that in combination, each element merely performs the same function as it does separately.
(3) One of ordinary skill in the art would have recognized that the results of the combination were predictable. One of ordinary skill in the art would expect that the resulting combination, a transdermal formulation in the form of an aqueous gel comprising L-DOPA, b-caryophyllene, eucalyptol, cannabidiol, and menthol performs all of the claimed functions. 1) One of ordinary skill in the art would expect that a transdermal formulation in the form of an aqueous gel comprising L-DOPA, b-caryophyllene, eucalyptol, cannabidiol, and menthol can be used to treat chronic pain, would have an analgesic component, and is configured for systemic and local treatment of chronic pain because transdermal CBD can treat pain, as evidenced by Fitzsimmons, L-dopa plus CBD can treat pain as evidenced by King BP, b-caryophyllene can treat pain, as evidenced by Scandiffio et al., eucalyptol can treat pain as evidenced by Vu et al., Giniger et al., and Mosbaugh et al., and menthol can treat pain as evidenced by Vaay, Vu et al., Giniger et al., Mosbaugh et al. and Fitzsimmons. 2) One of ordinary skill in the art would expect that a transdermal formulation in the form of an aqueous gel comprising L-DOPA, b-caryophyllene, eucalyptol, cannabidiol, and menthol can be used for hormone supplementation and that the L-dopa is sufficient to raise HGH levels because CBD can be used for hormone supplementation, as evidenced by Ligouri, and L-dopa can raise HGH levels, as evidenced by Supplements in Review, Nerenberg, and Quay et al. 3) One of ordinary skill in the art would expect the eucalyptol and menthol in a transdermal formulation in the form of an aqueous gel comprising L-DOPA, b-caryophyllene, eucalyptol, cannabidiol, and menthol would both alleviate localized pain and enhance passive transdermal delivery of the L-dopa because both functions are evidenced by the prior art of Fitzsimmons, Bundrla et al., Sudo et al, Zupan, Tsuk, Vaay, Vu et al., Giniger et al., Saroha et al., and/or Mosbaugh et al. Therefore, one of ordinary skill in the art would have recognized that the results of the combination were predictable.
(4) Whatever additional findings based on the Graham factual inquiries may be necessary, in view of the facts of the case under consideration, to explain a conclusion of obviousness. The specification does not include any objective evidence or reduction to practice that suggests an unexpected result.
The rationale to support a conclusion that the claim would have been obvious is that all the claimed elements were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combination yielded nothing more than predictable results to one of ordinary skill in the art. KSR, 550 U.S. at 416, 82 USPQ2d at 1395; B/E Aerospace, Inc. v. C&D Zodiac, Inc., 962 F.3d 1373, 1379, 2020 USPQ2d 10706 (Fed. Cir. 2020); Sakraida v. AG Pro, Inc., 425 U.S. 273, 282, 189 USPQ 449, 453 (1976); Anderson’s-Black Rock, Inc. v. Pavement Salvage Co., 396 U.S. 57, 62-63, 163 USPQ 673, 675 (1969); Great Atl. & P. Tea Co. v. Supermarket Equip. Corp., 340 U.S. 147, 152, 87 USPQ 303, 306 (1950). "[I]t can be important to identify a reason that would have prompted a person of ordinary skill in the relevant field to combine the elements in the way the claimed new invention does." KSR, 550 U.S. at 418, 82 USPQ2d at 1396.
Obviousness rationale teaching, suggestion, motivation in the art (MPEP § 2143.01(G))
It would have been obvious to one of ordinary skill in the art at the time the invention was filed to 1) select L-dopa as the additional active agent combined with CBD in the transdermal formulation taught by Fitzsimmons, 2) to further add b-caryophyllene to the CBD – L-dopa transdermal formulation taught by Fitzsimmons, 3) to further add eucalyptol to the CBD – L-dopa transdermal formulation taught by Fitzsimmons, and 4) to select menthol as an analgesic and for permeation enhancement to the CBD – L-dopa transdermal formulation taught by Fitzsimmons. The rationale for obviousness is some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention (MPEP § 2143.01(G)). The relevant findings for this rationale are as follows.
(1) There was some teaching, suggestion, or motivation, either in the references themselves or in the knowledge generally available to one of ordinary skill in the art, to modify the reference or to combine reference teachings. 1) One of ordinary skill in the art would have been motivated to select L-dopa as the additional active agent combined with CBD in the transdermal formulation taught by Fitzsimmons in view of specific teachings in the prior art. First, Fitzsimmons explicitly teaches the use the CBD formulations for treating Parkinson’s disease and the possible addition of L-dopa as an additional active agent for this purpose. The prior art of Sudo et al., Theobold et al., and King PD corroborate that L-dopa is a known treatment for this disease. Second, Sudo et al. teach that transdermal delivery of L-dopa is superior to oral and intravenous routes because Parkinson’s disease patient cannot comply with oral administration and sometimes pull out needles for injection. Third, King PD teach that CBD can mitigate the side effects of L-dopa in Parkinson’s treatment. 2) One of ordinary skill in the art would have been motivated to add b-caryophyllene to the CBD – L-dopa transdermal formulation taught by Fitzsimmons because Scandiffio et al. teach that β-caryophyllene is useful for treating pain and Parkinson’s disease. 3) One of ordinary skill in the art would have been motivated to add eucalyptol to the CBD – L-dopa transdermal formulation taught by Fitzsimmons because eucalyptol treats pain, as evidenced by Vu et al., Giniger et al., and Mosbaugh et al., and enhances permeation of active agents in transdermal formulations, as evidenced by Bundrla et al., Saroha et al., and Zupan. 4) One of ordinary skill in the art would have been motivated to add menthol to the CBD – L-dopa transdermal formulation taught by Fitzsimmons because menthol treats pain, as evidenced by Vaay, Vu et al., Giniger et al., Mosbaugh et al. and Fitzsimmons, and enhances permeation of active agents, including L-dopa, in transdermal formulations, as evidenced by Bundrla et al., Tsuk, Sudo et al., Saroha et al., and Fitzsimmons. Therefore, there was some teaching, suggestion, or motivation, either in the references themselves or in the knowledge generally available to one of ordinary skill in the art, to modify the reference or to combine reference teachings.
(2) There was reasonable expectation of success. One of ordinary skill in the art would expect that the resulting combination, a transdermal formulation in the form of an aqueous gel comprising L-DOPA, b-caryophyllene, eucalyptol, cannabidiol, and menthol performs all of the claimed functions. 1) One of ordinary skill in the art would expect that a transdermal formulation in the form of an aqueous gel comprising L-DOPA, b-caryophyllene, eucalyptol, cannabidiol, and menthol can be used to treat chronic pain, would have an analgesic component, and is configured for systemic and local treatment of chronic pain because transdermal CBD can treat pain, as evidenced by Fitzsimmons, L-dopa plus CBD can treat pain as evidenced by King BP, b-caryophyllene can treat pain, as evidenced by Scandiffio et al., eucalyptol can treat pain as evidenced by Vu et al., Giniger et al., and Mosbaugh et al., and menthol can treat pain as evidenced by Vaay, Vu et al., Giniger et al., Mosbaugh et al. and Fitzsimmons. 2) One of ordinary skill in the art would expect that a transdermal formulation in the form of an aqueous gel comprising L-DOPA, b-caryophyllene, eucalyptol, cannabidiol, and menthol can be used for hormone supplementation and that the L-dopa is sufficient to raise HGH levels because CBD can be used for hormone supplementation, as evidenced by Ligouri, and L-dopa can raise HGH levels, as evidenced by Supplements in Review, Nerenberg, and Quay et al. 3) One of ordinary skill in the art would expect the eucalyptol and menthol in a transdermal formulation in the form of an aqueous gel comprising L-DOPA, b-caryophyllene, eucalyptol, cannabidiol, and menthol would both alleviate localized pain and enhance passive transdermal delivery of the L-dopa because both functions are evidenced by the prior art of Fitzsimmons, Bundrla et al., Sudo et al, Zupan, Tsuk, Vaay, Vu et al., Giniger et al. and Mosbaugh et al. Therefore, there was a reasonable expectation of success.
(3) Whatever additional findings based on the Graham factual inquiries may be necessary, in view of the facts of the case under consideration, to explain a conclusion of obviousness. The specification does not include any objective evidence or reduction to practice that suggests an unexpected result.
The rationale to support a conclusion that the claim would have been obvious is that "a person of ordinary skill in the art would have been motivated to combine the prior art to achieve the claimed invention and whether there would have been a reasonable expectation of success in doing so." DyStar Textilfarben GmbH & Co. Deutschland KG v. C.H. Patrick Co., 464 F.3d 1356, 1360, 80 USPQ2d 1641, 1645 (Fed. Cir. 2006).
With respect to the newly added limitation in claim 1, Fitzsimmons exemplify compositions containing 2.5 % and 5% wt CBD (Tables 6-7, Examples). These values fall within the range “approximately 1% by weight”. In addition, MPEP § 2144.05(I) states that: “a prima facie case of obviousness exists where the claimed ranges or amounts do not overlap with the prior art but are merely close”. In the instant case, the prior art 2.5% and 5% w/w is close to the claimed range approximately 1% by weight.
Therefore, claim 1 is obvious over the cited art.
MPEP § 2144.05(I) states: In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976).
With respect to claim 11, Theobald et al. teach that the concentration of active agent may be 0.1 to 50%-wt., preferably 1 to 10%-wt (¶ [0048]). The claimed range 0.1% to 0.9 % overlap or lie inside the prior art range 0.1 to 50%-wt. Therefore, the claimed range is prima facie obvious over the prior art.
With respect to claim 12, Zupan teaches eucalyptol is at least 0.1% of the carrier when used as a permeation enhancer (claim 3). The claimed range 0.5% to 1.5 % overlap or lie inside the prior art range at least 0.1%. Therefore, the claimed range is prima facie obvious over the prior art.
With respect to claim 13, Fitzsimmons teaches menthol can be also be incorporated for cooling pain relief in an amount from about 0.1% w/w to about 1.0% w/w (para. [00102], [00176]) or 0.05 to 5% w/w (claim 41). In the instant case, the claimed range 2.5% to 3.5 % by weight overlap or lie inside the prior art range 0.05 to 5% w/w. Therefore, the claimed range is prima facie obvious over the prior art.
Claim 2 is rejected under 35 U.S.C. 103 as being unpatentable over the references cited above, as applied to claims 1 and 11-13, and further in view of Kumar et al (South Asian J. Food Technol. Environ. 1:116-121 (2015)).
The references do not explicitly teach a composition comprising a salicylic glycoside.
Kumar et al teach nutraceuticals for use in health and disease treatment and prevention. Nutraceuticals are substances which are not traditionally recognized nutrients but which have positive physiological effects on the human body. They are claimed to possess multiple therapeutic benefits. Medicinal plants represent one of the important fields of traditional medicine all over the world and hence an established constituents of nutraceuticals (p. 116). Nutraceuticals holds a great promise to improve health and prevent chronic diseases with the help of herbals. Some examples are willow bark (Salix nigra), having active component as salicin which is anti-inflammatory, analgesic, antipyretic, astringent and antiarthritic (p. 117). Kumar et al teach that nutraceuticals supplied through transdermal delivery would provide well targeted health benefits with optimal bioavailability (p. 120).
It would have been obvious to the skilled artisan to include salicin [reads on salicylic glycoside] in the cannabidiol transdermal formulations of Fitzsimmons et al. and Ligouri. The skilled artisan would have been motivated to do so because Kumar et al taught that salicin [or willow bark extract] was useful in reducing inflammation and pain, which were known to be associated with Parkinson’s disease, as taught by King PD. The skilled artisan would have had a reasonable expectation of success, because the references taught specific CBD gel formulations for transdermal administration.
Accordingly, claim 1 is rendered obvious by the teachings of the cited references.
Claims 3 is rejected under 35 U.S.C. 103 as being unpatentable over the references cited above, as applied to claims 1 and 11-13 above, and further in view of Schneider (U.S. 2021/0015763- previously cited).
The references do not explicitly teach inclusion of 2-5-dimethoxy-p-cymene in the CBD transdermal gel formulations.
Schneider teaches topical compositions comprising cannabidiol, menthol, camphor, an herb extract, and water (abstract, para. [0009], claim 1). Cannabidiol is a hydrophobic compound that is absorbed better through the skin than it is absorbed through the gut (para. [0018]). The CBD compositions of Schneider are topically administered (e.g., paras. [0018]-[0020]). Schneider teaches that herb extracts include Arnica Montana extract, in an effective amount to reduce or eliminate inflammation, pain, or both (paras. [0009-[0016], claims 4, 9, 11, and 14). As noted in the as-filed specification at para. [0150], 2,5-dimethoxy-p-cymene is naturally found in Arnica Montana extract.
It would have been obvious to the skilled artisan to include an Arnica Montana extract [reads on 2,5-dimethoxy-p-cymene] in the cannabidiol transdermal formulations of Fitzsimmons et al. and Ligouri. The skilled artisan would have been motivated to do so because Schneider taught that the extract could be formulated in a cannabidiol transdermal formulation and was useful in reducing inflammation and pain, which were known to be associated with Parkinson’s disease, as taught by King PD. The skilled artisan would have had a reasonable expectation of success, because the references taught specific CBD gel formulations for transdermal administration.
Accordingly, claim 3 is obvious in view the teachings of the cited references.
Response to Applicant’s Arguments
Applicant's arguments filed April 20, 2026, have been fully considered but they are not persuasive.
Applicant argues that “2.5% is not approximately 1% as 2.5% is two and half times larger than 1%” Reply 11. Further, Applicant argues that the Office action fails to provide a rationale for one of ordinary skill in the art to lower the CBD concentration from 2.5%, as taught by Fitzsimmons, to approximately 1%. This argument is not persuasive because it does not address the rationale of the rejection. MPEP § 2144.05(I) states that: “a prima facie case of obviousness exists where the claimed ranges or amounts do not overlap with the prior art but are merely close”. Applicant has failed to provide any evidence that the claimed amount is critical and results in unexpected properties or results.
Applicant argues that Fitzsimmons teaches a transdermal penetration mechanism that utilizes phosphatides and fatty acids, and that as a result, one of ordinary skill in the art would not consider eucalyptol and menthol for penetration enhancement as required by the claims. Reply 11. This argument is not persuasive because it does not address the rationale of the rejection. One of ordinary skill in the art would have been motivated to add eucalyptol to the CBD – L-dopa transdermal formulation taught by Fitzsimmons because eucalyptol treats pain, as evidenced by Vu et al., Giniger et al., and Mosbaugh et al., and enhances permeation of active agents in transdermal formulations, as evidenced by Bundrla et al., Saroha et al., and Zupan. In addition, one of ordinary skill in the art would have been motivated to add menthol to the CBD – L-dopa transdermal formulation taught by Fitzsimmons because menthol treats pain, as evidenced by Vaay, Vu et al., Giniger et al., Mosbaugh et al. and Fitzsimmons, and enhances permeation of active agents, including L-dopa, in transdermal formulations, as evidenced by Bundrla et al., Tsuk, Sudo et al., Saroha et al., and Fitzsimmons. Therefore, there was some teaching, suggestion, or motivation, either in the references themselves or in the knowledge generally available to one of ordinary skill in the art, to modify the reference or to combine reference teachings. In addition, one of ordinary skill in the art would expect the eucalyptol and menthol in a transdermal formulation in the form of an aqueous gel comprising L-DOPA, b-caryophyllene, eucalyptol, cannabidiol, and menthol would both alleviate localized pain and enhance passive transdermal delivery of the L-dopa because both functions are evidenced by the prior art of Fitzsimmons, Bundrla et al., Sudo et al, Zupan, Tsuk, Vaay, Vu et al., Giniger et al., Saroha et al., and/or Mosbaugh et al.
Applicant argues that the claims require “b-caryophyllene as a separate, discrete element of the analgesic component, distinct from CBD” whereas the Office action relies on b-caryophyllene as a component of a cannabis extract. Reply 11. Applicant further argues that the Office action does not “provide motivation to isolate it and include it as a separate, identified element”. Reply 12. This argument is not persuasive because the features upon which applicant relies (i.e., b-caryophyllene distinct from CBD) are not recited in the rejected claim(s). Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993).
Applicant argues that although Scandiffio discloses that b-caryophyllene has benefits for pain and Parkinson’s disease it does not teach nor suggest incorporating b-caryophyllene into a transdermal gel with L-DOPA, eucalyptol, CBD, and menthol. Reply 12. Applicant argues that hindsight reasoning is required to include it as a separate element in the claimed multi-component system. Reply 12. This argument is not persuasive because it argues the reference individually.
For these reasons, the rejection is maintained.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Applicant is reminded that for any amendments to the claims (including any new claim) that is not encompassed by the preexamination search and accelerated examination support documents previously filed, applicant is required to provide updated preexamination search and accelerated examination support documents that encompass the amended or new claims at the time of filing the amendment. Failure to provide such updated preexamination search and accelerated examination support documents at the time of filing the amendment will cause the amendment to be treated as not fully responsive and not to be entered. See MPEP § 708.02(a) subsection VIII.D. for more information.
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/CHRISTINA BRADLEY/Primary Examiner, Art Unit 1654
1 As evidenced by ChemSpider ID 5824, the Molecular Formula is C9H11NO4. The molecular weight is approximately 197 g/mol.
2 As evidenced by ChemSpider ID 5824, levodopa was also known in the prior art as L-DOPA. The Molecular Formula is C9H11NO4. The molecular weight is approximately 197 g/mol.
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