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 .
DETAILED ACTION
Response to Amendment
Acknowledgment is made of the receipt and entry of the amendment filed on July 10,2026, wherein new claims 28-36 are added, claims 2-5, 15, 18, and 19-21 are cancelled, and independent claims 1 and 17 are amended.
Election/Restrictions
Applicant elected Group II invention, and cannabigerolic acid (CBGA), having following structure, as the single disclosed species of the cannabinoid compound, in the reply filed 11/26/2025.
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Applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Claims 1, 6, 7, 9-13, 16 and 26-27 remain withdrawn from being directed to non-elected inventions.
Status of Claims
Claims 1, 6, 7, 9-13, 16, 17, and 23-36 are pending in instant application.
Claims 1, 6, 7, 9-13, 16 and 26-27 remain withdrawn from being directed to non-elected inventions/species.
Claims 17, 23-25 and 28-36 are currently under examination in this office action.
Priority
This application 18/033,187 filed on 04/21/2023 is a 371 of PCT/CA21/51487 filed 10/21/2021, which claims US provisional application No. 63/094,822 filed 10/21/2020.
Action Summary/Response to Argument
Applicant's remarks filed 07/10/2026 have been fully considered. Any objection and rejection found in the previous Office Action and not repeated herein has been withdrawn in view of amendment and Applicant’s persuasive arguments .The text of those sections of Title 35 U.S. Code not included in this action can be found in a prior Office action.
Claims 18-21 are cancelled and claim 17 is amended to recite CBGA at specific concentration. Rejections of claims 17-21 and 23-25 under 35 U.S.C. 102/ 103 over BARR (WO2020/092823 A1) is withdrawn.
As necessitated by amendment, rejections of claims 17, 23-25 and 28-36 under 35 USC § 112(a), 112(b) and 35 USC § 103 are modified/reapplied. Please see response to argument in following sections.
Claim Objections
Claim 30 is objected to because of following informalities:
Claim 30 recites an anti-aging mitochondrial ATP synthase modulator that is J147. Acronym “ J147” should be recited with a recognizable chemical name.
Claim Interpretation
Instant claims are amended to a method of promoting neurite elongation and/or restoring neurite formation in a patient in need thereof, comprising administering a therapeutically effective amount of a pharmaceutical formulation comprising CBGA or salt thereof, wherein the patient has a neuronal disorder and wherein the neuronal disorder is benefited or improved by neurite elongation and/or restoring neurite formation
The limitation “ promoting neurite elongation and/or restoring neurite formation” is construed as intended result of administering a therapeutically effective amount of a pharmaceutical formulation comprising CBGA or salt thereof in a patient in need thereof. The biological/pharmaceutical activities are the properties of compounds, and the products of identical or similar composition cannot exert mutually exclusive properties when administered under the same or similar circumstances. If prior art teaches a method of administering CBGA or salt thereof to a patient suffering from the recited neuronal disorder, the prior art is considered as read on instantly claimed method of promoting neurite elongation and/or restoring neurite formation even though the prior art is silent about promoting neurite elongation and/or restoring neurite formation.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
Claims 17, 23-25 and 28-36 are rejected under 35 U.S.C. 112(a), because the specification, while be enabling for a method of promoting neurite elongation and/or restoring neurite formation in-vitro with cannabigerolic acid CBGA at specific concentration, the specification does not enable a person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention in patients having variety of neuronal disorders that commensurate in scope with these claims. This is a scope of enablement rejection (modified/ reapplied as necessitated by amendment).
To be enabling, the specification must teach those skilled in the art how to make and use the full scope of the claimed invention without undue experimentation. In re Wright, 999 F.2d 1557, 1561 (Fed. Cir. 1993). The determination that "undue experimentation" would have been needed to practice the claimed invention in full scope is not a single, simple factual determination.
As stated in the MPEP 2164.01(a), “There are many factors to be considered when determining whether there is sufficient evidence to support a determination that a disclosure does not satisfy the enablement requirement and whether any necessary experimentation is "undue." In In re Wands, 8 USPQ2d 1400 (1988), factors to be considered in determining whether a disclosure meets the enablement requirement of 35 U.S.C. 112, first paragraph, have need described. They are:
(A) The breadth of the claims;
(B) The nature of the invention;
(C) The state of the prior art;
(D) The level of one of ordinary skill;
(E) The level of predictability in the art;
(F) The amount of direction provided by the inventor;
(G) The existence of working examples; and
(H) The quantity of experimentation needed to make or use the invention based on the content of the disclosure.
These factors are always applied against the background understanding that scope of enablement varies inversely with the degree of unpredictability involved. Keeping that in mind, the Wands factors are relevant to the instant application for the following reasons:
The Breadth of The Claims/ Nature of The Invention
Claim 17 is amended to recite a method of promoting neurite elongation and/or restoring neurite formation in the patients who have a neuronal disorder selected from a variety of disease, e.g. Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), Huntington's disease (HD), and multiple sclerosis (MS), motor neuron disease, axonal injury, schizophrenia, Down syndrome, and autism spectrum disorder (ASD). Claims 25 and 36 recite variety of administration route, systemically or locally including topically, inhalation, spray, etc.
The State of the Prior Art and the Predictability or Lack Thereof in the Art
Claim 17 is amended to recite the patients has a neuronal disorder selected from a variety of disease, e.g. Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), Huntington's disease (HD), and multiple sclerosis (MS), motor neuron disease, axonal injury, schizophrenia, Down syndrome, and autism spectrum disorder (ASD). It’s well-known these neuronal disease/ disorder have different etiology, different symptoms and treatment of these disease are very challenging and highly unpredictable. Although these neuronal disorders might benefit from promoting neurite elongation/restoring neurite formation, neurogenesis is dynamically regulated by numerous intrinsic and extrinsic factors, and complex interactions between different stages of neuronal development, which is highly unpredictable and challenging. The in-vitro assay data do not necessarily translate into in-vivo efficacy in patients having instantly claimed neuronal disease due to the blood-brain barrier and pharmacokinetic profile.
Regarding the effect of CBGA on neurons, there are contradictory study in the art. Echeverry (Neurotoxicity Research, 2021, 39:335–348) reviews the neuroprotective effect induced by Cannabidiol (CBD), Cannabigerol(CBG), and their respective acid forms, CBDA and CBGA at different concentration, wherein the ability to attenuate the neurotoxicity induced by two insults involving oxidative stress (hydrogen peroxide, H2O2) and mitochondrial dysfunction (rotenone) were evaluated in neural cell cultures (See whole article). No significant variation on cell viability was per se induced by the lower concentrations tested of CBD and CBG or CBDA and CBGA; however, high concentrations of CBD, CBDA, or CBGA were toxic since a 40–50% reduction of cell viability was observed (See abstract). Echeverry discloses CBGA was administered at 2.5, 5, 10, and 20 μM (See page 337, left column) while CBGA at 2.5 to 20 μM did not significantly affect the cell viability (See Results, page 337, right column, last para; page 338, right column; page 339, left column, Fig. 1d and 2d, Fig 6c, 7c).
Schubert (Molecular Neurobiology, 2019, 56, 7719–7730) reviews efficacy of cannabinoids in a pre-clinical drug-screening platform for Alzheimer’s disease(See whole article). Schubert discloses cannabigerolic acid (CBGA) was not able to sustain energy metabolism in the absence of glycolysis, and CBGA was not active in trophic support/ cell survival for E18 embryonic cortical neurons, and CBGA is universally toxic in all assays at 10 μM (See page 7721,right column; Table 1).
More generally, the invention is directed toward medicine and is therefore physiological in nature. It is well established that “the scope of enablement varies inversely with the degree of unpredictability of the factors involved,” and physiological activity (e.g., cancer prevention) is generally considered an unpredictable factor. See In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970).
The Amount of Direction Present and Presence or Absence of Working Examples
Instant specification disclosed in-vitro assay with cannabigerolic acid CBGA and other cannabinoid ( THC, CBD) at 0.15µM , 0.5 µM, 1.5 µM, 5 µM and 20 µM (See Examples 1-6). Instant Spec discloses CBGA increased neurite length in dose dependent manner(See Fig 12 and 14). Instant Example 7 is a study design for administration CBGA to AD rodent model without activity data. Instant Spec does not disclose any in-vivo assay wherein cannabigerolic acid CBGA was delivered to the affected neuron at the concentration between 0.15uM to 20uM in a patient having the recited neuronal disorders wherein the symptoms of patient are improved. Instant specification does not disclose any in-vivo assay that support the administration route in claim 25 and 33, e.g. topically, inhalation, spray, etc. that could provide the effective amount of CBGA at 0.15uM to 20uM to the affected neuron. Due to the blood-brain barrier, an ordinary skilled person in the art would not know if CBGA could be administered through the instantly claimed route (e.g. topically, etc. ) to provide CBGA at 0.15uM to 20uM to the affected neuron for the intended treatment outcome. An ordinary skilled in the art would not know how to control the amount of CBGA in the formulation administered through different route so that it could reach the affected neuron at concentration between 0.15uM to 20uM, while not above 20uM or below 0.15uM. Instant Spec does not disclose working example of CBGA in combination with other active agent as recited in claim 30.
The level of one of ordinary skill in the art
The level of skill required to use the instant invention would likely require many years of professional experience conducting research in the art (e.g. medicine, pharmaceutical science, biology, biochemistry, medicinal chemistry, etc.) as well as an advanced educational degree (e.g., M.D. and/or Ph.D.) commensurate in level with the advanced techniques involved in the preparation and/or use of the instant invention.
The quantity of experimentation needed
An unduly extensive amount of experimentation would be required for one of ordinary skill in the art to use the claimed invention in full scope. Working examples or in-vivo study would need to be explored for treating patients having various neurological disease. The therapeutically effective amount may vary depending on many factors, such the subjects being treated, the disease condition, administration route, and intended treatment outcome, etc. Therefore, it would be a great burden for one of ordinary skill in the art to carry out undue experimentation to use the claimed invention in full scope.
Conclusion
MPEP 2164.01(a) states, “A conclusion of lack of enablement means that, based on the evidence regarding each of the above factors, the specification, at the time the application was filed, would not have taught one skilled in the art how to make and/or use the full scope of the claimed invention without undue experimentation. In re Wright, 999 F.2d 1557,1562,27 USPQ2d 1510, 1513 (Fed. Cir. 1993).” That conclusion is clearly justified here with respect to the claimed method of promoting neurite elongation and/or restoring neurite formation in variety of subjects, in view of the analysis above pursuant to In re Wands. In other words, one skilled in the art could not practice the claimed invention in full scope without undue experimentation.
Response to Arguments
Applicant argues that claim 17 relates to a method of promoting neurite elongation and/or restoring neurite formation, administering CBGA or a salt thereof a therapeutically effective amount that provides a concentration of from about 0.15 μM to less than 20 μM of CBGA or a salt in contact with the neurons, which can achieve the desired effect supported by the examples in specification and the state of the art.
RESPONSE: Applicant’s argument is considered, but not found persuasive. As elaborated above, there are contradictory study regarding the effect of CBGA on neurons in the art. Instant Spec does not provide any in-vivo assay wherein cannabigerolic acid CBGA was delivered to the affected neuron at the concentration between 0.15uM to 20uM in a patient having the recited neuronal disorders wherein the symptoms of patient are improved. Due to the contradictory study in prior art and high unpredictability of treating variety of neuronal disease in patients, the 112(a) rejection is reapplied.
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
Claims 17, 23-25, 30-32, and 34-36 are rejected under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention (newly applied necessitated by amendment).
Claim 17 is amended to recite a method of promoting neurite elongation and/or restoring neurite formation in a patient in need thereof, comprising administering a therapeutically effective amount of a pharmaceutical formulation comprising CBGA or salt thereof wherein the therapeutically effective amount provides a concentration of from about 0.15 uM to less than 20 uM of the cannabinoid compound in contact with the affected neurons, wherein the patient has a neuronal disorder selected from the group consisting of Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), Huntington's disease (HD), and multiple sclerosis (MS); or wherein the patient has a neuronal disorder that is selected from the group consisting of a motor neuron disease, axonal injury, schizophrenia, Down syndrome, and autism spectrum disorder (ASD); and wherein the neuronal disorder is benefited or improved by neurite elongation and/or restoring neurite formation
The limitation regarding targeted neuronal disorder is ambiguous. The motor neuron disease is considered as broad limitation comprising different neuronal disorders, e.g. amyotrophic lateral sclerosis (ALS), Spinal muscular atrophy (SMA), etc. A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c).
Claims 23-25, 31-32, and 34-36 are rejected due to dependency of claim 17.
Claim 30 contains the trademark/trade name Namenda®. Where a trademark or trade name is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph. See Ex parte Simpson, 218 USPQ 1020 (Bd. App. 1982). The claim scope is uncertain since the trademark or trade name cannot be used properly to identify any particular material or product. A trademark or trade name is used to identify a source of goods, and not the goods themselves.
Claim 31 recites limitation wherein the therapeutically effective amount provides a concentration of about 0.5 µM to about 15 µM of the cannabinoid compound in contact with the affected neurons, or about 1.5 µM to about 15 µM of the cannabinoid compound in contact with the affected neurons, or about 5 µM to about 15 µM of the cannabinoid compound in contact with the affected neurons. A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c).
Claim Rejections - 35 USC§ 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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 35 U.S.C. 103 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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 17, 23-25 and 28-36 are rejected under 35 U.S.C. 103 as being unpatentable over Arnold et al. ( WO2019071302A1) and Stone et al. (British Journal of Pharmacology, Volume 177, Issue 19 Oct 2020, pages 4311-4560, first published July 2020, https://doi.org/10.1111/bph.15185A, “A systematic review of minor phytocannabinoids with promising neuroprotective potential”) and Nadal et al. (British Journal of Pharmacology (2017) 174 4263–4276 , DOI:10.1111/bph.14019, Tetrahydrocannabinolic acid is a potent PPARγ agonist with neuroprotective activity))(reapplied as necessitated by amendment).
Arnold teaches a method of treating neurological disorder (e.g. seizure), comprising administering to the individual a therapeutically effective amount of cannabigerolic acid (See whole article; abstract, page 2, lines 18-30; Examples 1-4; claims 1- 20). Arnold teaches cannabinoid family (e.g. CBD, CBGA, etc.) (See page 20 ) and explicitly teaches CBGA prevents or reduce the frequency of seizures, or reduce the severity of seizures in an individual in need thereof (See abstract, page 5, lines 10-15; Examples 1-4, Figure 1). Arnold teaches CBGA displays anticonvulsant properties by increasing tolerability to hyperthermia-induced seizures in two genetically distinct mouse models of Dravet syndrome(See Example 1, Figure 1, page 27, lines 17-25). Arnold also teaches CBGA is more effective in modulating seizures at a lower dose than CBD, a known anticonvulsant, indicating that CBGA may be a superior anticonvulsant, particularly in the context of Dravet syndrome (See page 27, lines 17-25).
Arnold teaches CBGA formulation can be adapted for administered through variety of routes, e.g. parenteral administration, such as intravenous, intraarterial, intramuscular, intrathecal, subcutaneous or intraperitoneal injection, intranasal, gastrointestinal, or other commonly used routes for administration (See page 23, lines 16-20)(which reads on claim 25, 34 and 36). Arnold teaches various dosage regimen of CBGA from about 0.5 mg/kg to about 50 mg/kg, e.g. 10mg/kg, 30mg/kg(See page 24, last para; page 27, first para; Figure B). Arnold teaches therapeutically effective amount of CBGA may be administered to a subject once a day, twice a day, or three times a day (See page 25, lines 1-4)(which reads on claim 35).
Arnold teaches epilepsy is a neurological disorder that is associated with neuronal activity in the brain (See page 8, lines 24-30). Arnold is silent about CBGA for promoting neurite elongation and/or restoring neurite formation. However, The biological/ pharmaceutical activities are the properties of compounds, and the products of identical or similar composition cannot exert mutually exclusive properties when administered under the same or similar circumstances.
Stone reviews neuroprotective potential for phytocannabinoids, e.g. cannabidiol (CBD),
Δ9-tetrahydrocannabinol, cannabigerolic acid, etc. in variety of neuronal diseases (See abstract, whole article, Table 1). Stone teaches Δ9-THC and CBD are well studied and established for neuroprotective properties in variety of neurological diseases, e.g. Parkinson's, Alzheimer's and Epidiolex® (pure CBD) is licensed to treat Lennox–Gastaut syndrome and Dravet syndrome, which are severe forms of childhood epilepsy (See page 4331, left column; Table 1). Stone and its incorporated reference teach CBGA interact with various TRP channel isoforms including TRPV1, TRPV2,TRPA1, and TRPM8 channels that are involved in a wide range of neurological disorders . For example,TRPA1-deficient mice were more likely to sustain damage post ischemia and TRPA1 channel activation in Alzheimer's disease may have a crucial role in regulating astrocyte-mediated inflammation (See page 4347, right column, 2nd para).
Nadal teaches phytocannabinoids ( Δ9 -THC, cannabidiol CBD and CBG) and their corresponding acidic precursors (Δ9 -THCA, cannabidiol acid (CBDA) and cannabigerol acid (CBGA), respectively) as agonists of PPARγ with neuroprotective activity for the treatment of Huntington's Disease (HD disease) and possibly other neurodegenerative, metabolic and inflammatory diseases (See whole article, abstract, page 4264, right column).
Regarding instant claimed neuronal disease, Nadal and incorporated reference teach PPARγ ligands may exert beneficial effects in many CNS diseases such as amyotrophic lateral sclerosis, Parkinson’s disease, Alzheimer’s disease, Huntington's Disease (HD), multiple sclerosis and stroke (See page 4269, right column) and explicitly teaches neuroprotective mechanism of PPARγ agonist in Huntington's Disease (See introduction, page 4264, left column). Nadal teaches CBGA at various concentration (0.1uM, 1uM, 5uM, 10uM and 25uM) outperformed corresponding neutral CBG and showed potency in binding and activating PPARγ (See page 4266, right column; Results; page 4268 Fig 2.).
CBGA is structurally related to neuroprotective cannabinoid CBD and THC as taught by Stone. Given the beneficial effects of CBGA in neuronal disease established by Arnold and Nadal, it would have been prima facie obvious for an ordinary skilled artisan to further explore CBGA or salt thereof for neuroprotective properties in neuronal disease and reasonably expect that CBGA or salt thereof may provide alternative treatment in other neuronal disease (e.g. Alzheimer's).
Regarding claim 30, combination therapy is common practice in treatment for neuronal diseases and Namenda ®(memantine) is a standard FDA-approved drug for Alzheimer’s disease. A skilled artisan would be motivated to combine CBGA with memantine and reasonably expect combination of CBGA with memantine would provide alternative treatment for Alzheimer’s patient.
One of ordinary skill in the art would have had reasonable expectation of success in producing the claimed invention based on the combined teachings of prior art, together with further exploration/optimization based on general knowledge of cannabinoid and neurological disease treatment . Therefore, the invention as a whole is prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
Response to Arguments
Applicant argues claim 17 recites "restoring neurite formation" , "the neuronal disorder is benefited or improved by promoting neurite elongation and/or restoring neurite formation." ... Arnold provides no support for the alleged "neurite formation" or "promoting neurite elongation and/or restoring neurite formation" (Remarks, page 18-19).
RESPONSE: Applicant’s argument is considered, but NOT persuasive. A recitation of the intended use of the claimed invention must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. If the prior art structure is capable of performing the intended use, then it meets the claim. The biological/ pharmaceutical activities are the properties of compounds, and the products of identical or similar composition cannot exert mutually exclusive properties when administered under the same or similar circumstances. In other words, even though the prior art is silent about promoting neurite elongation and/or restoring neurite formation, by administrating CBGA or salt thereof to an individual in need thereof, one will also be promoting neurite elongation and/or restoring neurite formation even though the prior art was not aware of it. Further, Nadal teaches neuroprotective activity of CBGA through modulation of PPARγ pathways that might be beneficial in neuronal disease, e.g. Huntington's Disease (HD), Alzheimer’s disease, epilepsy, etc. Stone teaches CBGA interact with TRP channel that might be beneficial in neuronal disease such as Alzheimer's disease. It’s common practice to explore/repurpose active ingredient for treating different disease/disorder.
Applicant argues Stone does not teach the neuroprotective effect of CBGA and may provide the opposite of Arnold's intended effect (Remarks, page 24-25).
RESONSE: Stone and its incorporated reference teaches neuroprotective properties of cannabinoid through different pathways in variety of neuronal disease including epilepsy, Alzheimer’s, Huntington Disease, etc. ( See Table 1). Stone teaches CBGA interact with TRP channel that might be beneficial in neuronal disease such as Alzheimer's disease. An active ingredient might be associated with multiple pathways and it’s common practice to explore/repurpose active ingredient for treating different disease/disorder. Such investigation does not require the active ingredient produce the same effect through the same mechanism.
Applicant argues about the CBGA concentration: “ The claimed concentration range is the amount in contact with the neuron, not the amount in the formulation” (Remarks, page 20).
RESPONSE: Even instant claimed concentration is the amount in contact with the neurons, the amount reaching and contacting the neuron cells depends on the delivery route, the formulation and variety of factors. Instant claimed variety of administration route (e.g. topically, spray) lacks sufficient support by instant disclosure might not deliver effective concentration of CBGA in contact with the affected neurons as claimed. Although Arnold does not expressly disclose the claimed concentration at the cellular level, in practice, a skilled artisan would have known to experiment/optimize the amount of CBGA associated with different delivery route to achieve a desired concentration at the target neuron. Further, Nadal teaches CBGA at a concentration at 0.1uM, 1uM, 5uM, 10uM and 25uM.
Applicant recites data from instant Examples 1-7 (Remarks, page 21-22) and argues against Arnold and Nadal: “ CBGA did not surpass binding affinity over the control for PPAR-y until high concentrations (Nadal, FIG. IC). Increases in activation of PPAR-y with CBGA only occurred at high concentrations (25 μM, id.)... the person of ordinary skill in the art would have doubts about whether CBGA would have an effect on neurons, much less at the claimed concentration range in contact with the affected neurons, and accordingly, based on Nadal, would not be motivated to select CBGA for further experimentation (Remarks, page 25).
RESPONSE: Applicant’s argument is considered, but NOT persuasive. The absence of instantly claimed effect by CBGA in prior art does not render instantly claimed use unobvious. As MPEP 2143.02.I. stated : “Conclusive proof of efficacy is not required to show a reasonable expectation of success. OSI Pharm., LLC v. Apotex Inc., 939 F.3d 1375, 1385, 2019 USPQ2d 379681 (Fed. Cir. 2019) ("To be clear, we do not hold today that efficacy data is always required for a reasonable expectation of success. Nor are we requiring ‘absolute predictability of success.’"); Acorda Therapeutics, Inc. v. Roxane Lab., Inc., 903 F.3d 1310, 1333, 128 USPQ2d 1001, 1018 (Fed. Cir. 2018) ("This court has long rejected a requirement of ‘[c]onclusive proof of efficacy’ for obviousness." (citing to Hoffmann-La Roche Inc. v. Apotex Inc., 748 F.3d 1326, 1331 (Fed. Cir. 2014); PharmaStem Therapeutics, Inc. v. ViaCell, Inc., 491 F.3d 1342, 1364 (Fed. Cir. 2007); Pfizer, Inc. v. Apotex, Inc., 480 F.3d 1348, 1364, 1367–68 (Fed. Cir. 2007) (reasoning that "the expectation of success need only be reasonable, not absolute"))”.
Conclusion
No claims are allowed
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to LIYUAN MOU whose telephone number is (571)270-1791. The examiner can normally be reached Mon-Fri 9:00-5:30.
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/LIYUAN MOU/
Examiner, Art Unit 1628
/JARED BARSKY/Primary Examiner, Art Unit 1628
