The 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 03/16/2026, wherein claim 1 is amended, claims 2, 5, 7-10 and 23-38 are cancelled.
Election/Restrictions
Applicant elected with traverse in the reply filed 10/14/2025: Group I, drawn to a method for the treatment of Tourette syndrome in a subject comprising administering a composition comprising therapeutically effective amount of cannabidiol CBD; and species:
1) bovine gelatin and mannitol as binder and/or excipient system:
2) a dopamine precursor as drug to be combined with CBD;
3) an abnormal involuntary movement as subjects of Tourette syndrome;
4) a pediatric autoimmune disorder associated with streptococcal infection (PANDAS) as subjects of Tic disorder having different conditions.
The Restriction requirement was made Final in last office action mailed on 12/16/2025. Claims 41-46 remain withdrawn from consideration pursuant to 37 CFR 1.142(b), as being drawn to nonelected inventions/species.
Status of Claims
Claims 1, 3-4, 6, 11-22, 39-46 are pending.
Claims 41-46 remain withdrawn.
Claims 1, 3-4, 6, 11-22, 39-40 are under examination in this office action.
Priority
The instant application 18/317,977 filed on 05/16/2023, claims benefit of US provisional application No. 63/342,925 filed 05/17/2022.
Claim Interpretation
Instant claims are directed to a method for the treatment of Tourette syndrome in a subject, the method comprising: administering to the subject in need thereof, via the oral mucosa, a rapidly infusing composition comprising (a) a pharmaceutically acceptable binder and/or excipient system comprising gelatin and a sugar alcohol, and (b) a therapeutically effective amount of cannabidiol (CBD).
Instant claims 1, 3-4, 6, 11- 16 recite limitation directed to the composition comprising CBD. Instant claims 17-22 recite limitation related to administration of composition comprising CBD.
Please note the biological activity is the property of compound. “[T]he discovery of a previously unappreciated property of a prior art composition, or of a scientific explanation for the prior art’s functioning, does not render the old composition patentably new to the discoverer.” Atlas Powder Co. v. Ireco Inc., 190 F.3d 1342, 1347, 51 USPQ2d 1943, 1947 (Fed. Cir.1999). If the prior art teaches and suggests the same method step as instantly claimed (administering a composition comprising CBD to a subject suffering Tourette syndrome), the method of the prior art would have achieved the intended results as recited in instant claims and read on instant claimed methods. The burden of proof is shifted to the Applicant to show that the subject matter of the prior art does not possess the characteristic property of instantly claimed method.
Action Summary
Applicant’s Remarks filed 03/16/2026 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 remarks .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 31-38 are cancelled, thus, written description rejection of claims 1, 31- 38 is withdrawn.
Applicant filed Terminal Disclaimer over US patent No. 11672761 and copending US application No. 18252668; 18252693, 18253694, 18252741 and 18317964 on 03/16/20226. Thus, the rejections on the ground of non-statutory double patenting over US patent No. 11672761 and copending US application No. 18252668; 18252693, 18253694, 18252741 and 18317964 are withdrawn.
Applicant's arguments filed 03/16/2026 have been fully considered, but they are NOT persuasive to overcome enablement rejection under 35 U.S.C. 112(a) and rejections under 35 U.S.C. 103: 1) claims 1, 3-4, 11-15, 18-22, 39-40 rejected as being unpatentable over Mukunda in view of Kumar and Novotny; 2) claims 1, 3-4, 6, 11-22, 39-40 rejected as being unpatentable over Mukunda, in view of Kumar, Grother and Novotny. Applicant’s argument against individual reference on the record are addressed accordingly.
35 USC §112(a)
Applicant’s statement of interview on March 10, 2026 is inaccurate. The examiner did not agree the proposed amendments would overcome the Enablement and Written Description under 35 USC §112 (a). The examiner only indicated instant Spec might satisfy the written description for the symptoms that are associated with Tourette syndrome recited in claims 22-30 based on the search of prior art. Now claims 31-38 are cancelled, written description rejection of claims 1 and 31- 38 are withdrawn. The examiner only indicated the proposed amendment narrows scope of formulation and would be searched and reconsidered for enablement for instantly claimed method of treating Tourette syndrome with instantly claimed CBD composition via mucosa.
As explained in the Examiner’s interview summary, claim 1 reciting composition comprising CBD, gelatin and sugar alcohol without any dose limitation is very broad for the claimed dissolution profile and method of treating Tourette syndrome, and Applicant is advised to provide support for instantly claimed method of treating Tourette syndrome with instantly claimed CBD composition with recited dissolution profile via mucosa since instant spec does not disclose any working example/ assay of treating Tourette syndrome and efficacy thereof. As Applicant later argues based on Seager's teaching, primary challenge of mucosa delivery of CBD is CBD’s poor water solubility. Itin et al. (2020) also discusses the challenge/prolonged mucosa delivery of cannabidiol and its tendency to linger and accumulate in the mucosal tissue rather than being absorbed. Applicant did not provide any more evidence and data to support instantly claimed CBD composition with recited dissolution profile could be delivered via mucosa for method of treating Tourette syndrome. Due to the high unpredictability of treating Tourette syndrome and lack of sufficient support of working example by instant disclosure , the enablement rejection under 35 USC 112(a) is maintained/reiterated as necessitated by amendment.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(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 1, 3-4, 6, 11-22, 39-40 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the enablement requirement. The claims contain subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention.
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
Instant claims are directed to a method for the treatment of Tourette syndrome in a subject, the method comprising: administering to the subject in need thereof, via the oral mucosa, a rapidly infusing composition comprising a therapeutically effective amount of cannabidiol (CBD).
The State of the Prior Art and the Predictability or Lack Thereof in the Art
Tourette syndrome is a complex disorder and the cause of TS is not yet known. It is well known in the prior art that treatment of Tourette syndrome, is challenging and highly unpredictable. Novotny (2018) reviews epidemiology, pathophysiology, diagnosis, and treatment of Tourette syndrome (TS) and concludes “Even though more than 130 years have passed, since the TS in 1885, there are still many unanswered questions. The exact cause of changes in brain tissue remains unknown. Similarly, highly effective, targeted, and safe therapy is still unavailable. Concerning TS therapy, there are still several controversial topics, their main denominator is the lack of clinically relevant studies or comparative studies” (See page 4, Conclusion).
Seideman (2020) reviews etiology, pharmacologic and non- pharmacologic treatment of Tourette syndrome (See whole article). Seideman teaches “Studies are challenged by the complexity of the disorder, the periodic waxing and waning of symptoms, the presence of associated comorbidities (e.g., ADHD and obsessive-compulsive disorder), and the lack of definitive target receptors for treatment. Only 3 agents (i.e., haloperidol, pimozide, and aripiprazole) have been approved by the FDA for the suppression of Tourette syndrome–related tics”( See page 402, left column). Seideman teaches use of cannabinoids (e.g. THC) treating Tourette syndrome, but concluded that “although some positive outcomes were reported, the size of the studies and potential biases did not provide enough evidence to
warrant recommending cannabinoid treatment for tic reduction in adults” (See page 402, left column, page 407 right column).
Szejko (2022) reviews cannabis-based medicine in treatment of patients with Gilles de la Tourette syndrome (See whole article). Szeiko teaches “CBM should still be regarded as an experimental treatment in patients with GTS, as suggested by the 2019 guidelines of the AAN and the 2021 guidelines of the ESSTS. A recently published meta-analysis examining the potential therapeutic benefits of CBM in psychiatric disorders in general, including GTS, demonstrated limited evidence for their effectiveness due to a lack of robust data from RCTs . Moreover, the results of RCTs are conflicting, as smaller studies with THC showed significant tic reduction, while another study using the endocannabinoid modulator Lu AG06466 failed to demonstrate efficacy in tic reduction” (See Conclusion, page 36).
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 discloses examples of composition comprising CBD (See page 60, Examples, Table 1 and 2) and seal integrity test was performed at -0.5 Bar for 30 seconds, 1-minute soak time (See US PGPUB 2024/0000810 A1 [0213]). However, instant specification does not disclose any assay related to treating Tourette syndrome, or ameliorating symptom of Tourette syndrome, e.g. an abnormal involuntary movement, etc.. The clinical trial results incorporated from U.S. patent application No. 17/225,738 (See page 64) are directed to post-surgical pain following shoulder arthroscopy which is NOT related to instantly claimed method of treating Tourette syndrome. Instant specification disclosed Epidiolex®, FDA- approved drug containing CBD for treating disease/disorder (See page 64, [0143]), which is NOT related to instantly claimed method of treating Tourette syndrome with instantly claimed composition comprising CBD. In absence of any assay related to Tourette syndrome disclosed by instant specification, an ordinary skilled in the art would not know if instantly claimed method of treating Tourette syndrome could be practiced by administering instantly claimed composition comprising CBD via mucosa.
The level of one of ordinary skill in the art
The level of skill required to make and/or use the instant invention would likely require many years of professional experience conducting research in the art (e.g., medicine, pharmaceutical science, biology, biochemistry, 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 would be needed to determine the efficacy of instantly claimed method of treating Tourette syndrome with instantly claimed CBD composition, e.g. evaluation and measurement of variety treatment outcome. The therapeutically effective amount may vary depending on many factors, such the subjects being treated/the disease condition associated with Tourette syndrome, e.g. attention deficit hyperactivity disorder, obsessive-compulsive disorder, and autism spectrum disorder, etc. and intended treatment outcome (e.g. tic severity). 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 treating Tourette syndrome with instantly claimed CBD composition via mucosa 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.
Claim Rejections - 35 USC § 103
Modified/reiterated as necessitated by Amendment
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 1, 3-4, 11-15, 18-22, 39-40 are rejected under 35 U.S.C. 103 as being unpatentable over Mukunda et al. (WO 2020237247 A1), in view of Kumar et al. (WO2021028943A1) and Novotny et al.(Frontiers in Neurology, 2018, 9:139, doi: 10.3389/fneur.2018.00139, Tourette Syndrome: A Mini-Review)(reiterated as necessitated by amendment).
Regarding claim 1, Mukunda teaches a method of treating Tourette syndrome (TS) in human with formulation comprising cannabis compound (e.g. CBD) (See summary, Examples 1-8, claims 1-14).
Regarding the administration limitation of instant claims 18-22, Mukunda teaches oral dose of CBD 0.2 µg/kg to about 0.035 mg/kg or 2.5mg CBD (See page 7, Table 1 and Table 2, claims 8, 10). Mukunda teaches oral dose is administered twice a day, thrice a day or four times a day depending on the severity of the symptoms comprising of a cannabis compound with up to 2.5 mg CBD (See page 8, para 2; Examples 1-8).
Regarding claim 21, Mukunda teaches patient is administered cannabis formulation without THC component(See Example 6, 8-10).
Regarding the symptoms of Tourette syndrome (TS), Mukunda and its incorporated reference teach Tourette syndrome (TS) is a childhood onset, neurobehavioral disorder and characterized by motor and vocal tics, and associated with a wide spectrum of behavioral and cognitive alterations…Most patients suffer from psychiatric comorbidities such as attention deficit hyperactivity disorder (ADHD), obsessive compulsive disorder (OCD), self-injurious behavior, depression, and anxiety
disorder… More adversely affected patients usually display more complex tics including
imitating gestures (echopraxia) and words or phrases (echolalia), and paliphenomena
such as phonic blocking and repetition of own words and syllables (palilalia)… (See page 1-2 ). Mukunda teaches the symptoms of TS patient, e.g. multiple motor and vocal tics, ADHD, OCD, etc. ( See Examples 1-8).
Regarding the treatment of Tourette syndrome and outcome measurement, Mukunda explicitly teaches patient administered cannabis formulation without THC three times a day showed decreased in ADHD, OCD symptoms (See Example 6) , Speech Efficiency Score (SES) scale of 11 improved to score of 6 (See Example 10). Mukunda and its incorporated reference teach traditional treatment, e.g. behavioral therapy and antipsychotic medication according to European clinical guidelines for Tourette syndrome and other tic disorders (See page 4-5). Mukunda and its incorporated reference teach the central endocannabinoid system (ECS) has been proposed as an alternative mechanism of drug action, wherein cannabis-based medicine (CBM) such as dronabinol (delta-9- tetrahydrocannabinol, THC) and nabiximols which contains THC and cannabidiol (CBD) at a 1: 1 ratio-have been suggested as new treatment strategies for patients with TS and case report wherein patient showed a rapid and highly significant improvement in the Yale Global Tic Severity Scale (See page 6). As elaborated in Claim Interpretation section, the recitation of symptoms of Tourette syndrome and treatment outcome do not materially limit the claimed method since such limitations do not result in manipulative difference in method steps of the claims. A skilled artisan would have known the symptoms of Tourette syndrome (TS) and measurement/evaluation of treatment outcome as demonstrated in Mukunda and its incorporated references.
Regarding claim 40, Mukunda teaches CBD could be combined with atypical antipsychotic drug, e.g. risperidone, clozapine, olanzapine, ziprasidone, and aripiprazole, etc. (See Examples 8-10, claim 12).
Mukunda is silent about gelatin and sugar alcohol and other limitation directed to the CBD composition.
Regarding limitation directed to CBD composition, Kumar teaches cannabidiol orally rapidly disintegrating/sublingual dosage comprising binding agent (e.g. gelatin) and structure forming agent (e.g. mannitol) (See abstract, page 3, para 2, claims 1-11).
Regarding limitation of gelatin, Kumar teaches lyophilized, oral, solid, rapidly disintegrating tablets comprising cannabidiol, fish gelatin as the matrix forming agent, a dispersing agent and a structure forming agent for rapid dispersion( page 13, para 1). Kumar also teaches fish gelatin as binding agent(See claims 6 and 12). The bovine gelatin recited in instant claim 6 is considered as equivalent of fish gelatin taught by Kumar.
Regarding the limitation of sugar alcohol, Kumar teaches mannitol as structure forming agent/binder (See abstract, page 8, para 4; Examples 1-8).
Regarding the concentration of cannabidiol, mannitol and gelatin, Kumar teaches the amount/concentration of cannabidiol at 1% to 50% by weight of the composition; b) binding/matrix forming agent (e.g. gelatin) in a concentration ranging from 0.2% to 12% by weight of the composition, c) structure forming agent(e.g. mannitol) in a concentration ranging from 2% to 10% by weight of the composition(See page 6, para 3; claim 1). Kumar also teaches variety of concentration of CBD and mannitol in Examples 1-6. Where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation. MPEP 2144.05
Regarding claims 3-4, Kumar teaches orally disintegrating tablet dosage forms of cannabidiol (CBD), prepared by a process of lyophilization, wherein the lyophilized dosage form disintegrates in the mouth in less than 10 seconds, or 5-10 seconds (See page 3, para 2; page 6, para 2; page 18, para3; page 20, para 2; Examples 4-5 ).
Regarding claim 12, Kumar teaches embodiments comprising cannabidiol at size of 60 nanometer to 5 microns (See page 23, para 2).
Regarding claim 13-16, Kumar teaches embodiments comprising sweetener (e.g. aspartame), flavoring agent, colorants, taste-masking agents, etc. (See page 6, para 5; page 14, para1; Examples 1-6). It’s noted the flavoring agent (lemon-lime flavor), colorant (yellow #5) or sweetener are not considered as contributing to structure limitation / patentable weight of the orally disintegrating tablet dosage forms of cannabidiol and method of treating disease with the cannabidiol. A skilled artisan would have known to select different flavoring agent, sweetener or colorant.
Regarding the limitation of oral mucosa/ buccal mucosa of claim 17, Kumar teaches lyophilized sublingual tablet administration (See Example 6; page 20). A skilled artisan would know buccal mucosa is part of oral cavity and oral disintegrating tablet could be administered by oral mucosa/ buccal mucosa.
Regarding claim 21, Kumar teaches CBD isolated is the only active therapeutic agent in Examples 1-8.
Kumar is silent about solid form of cannabidiol and purity thereof recited claim 11. A skilled artisan would have known to incorporate high purity cannabidiol solid for the CBD orally disintegrating tablet. Kumar collectivity teaches CBD orally disintegrating tablet that read on instantly claimed rapid infusing composition.
Novotny reviews epidemiology, pathophysiology, diagnosis, and treatment of Tourette syndrome (TS)(See whole article). Novotny teaches symptoms of Tourette syndrome(See Table 1). Novotny teaches tic severity and frequency in Tourette syndrome are evaluated/assessed based on Premonitory Urges for Tics Scale and Yale Global Tic Severity Scale (YGTSS) of tics (See Diagnosis). Novotny teaches deep brain stimulation (DBS) as treatment for Tourette syndrome ( See page 3, Treatment/ Surgery) (which read on instant claim 39).
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Mukunda teaches a method of treating Tourette syndrome (TS) in human with a formulation comprising cannabis compound (e.g. CBD). Kumar teaches CBD orally disintegrating tablet that rapidly disintegrates in mouth. It would have been prima facie obvious to one of ordinary skilled in the art before the effective filing date of the instant invention to incorporate the rapidly disintegrating CBD formulation taught by Kumar for method of treating Tourette syndrome as taught by Mukunda, together with experimentation/ optimization based on the general knowledge of Tourette syndrome treatment (e.g. symptoms, treatment outcome, etc.) as taught by Novotny (2018) and pharmaceutical composition(e.g. orally disintegrating dosage form). The skilled artisan would be motivated to do so because rapidly disintegrating dosage form is commonly known to provide advantages over conventional dosage form, e.g. rapid disintegration, rapid onset of action, etc. A skilled artisan would reasonably expect the rapidly infusing composition comprising CBD would provide fast action of CBD for treating Tourette syndrome (TS).
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 experimentation/ optimization based on the general knowledge of Tourette syndrome treatment (e.g. symptoms, treatment outcome, etc.) and pharmaceutical composition(e.g. orally disintegrating dosage form). 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 Argument
Applicant argues against each reference on the record and alleged Mukunda, Kumar, and Novotny, alone or in combination, fail to teach, show, suggest, or otherwise render obvious claim 1 and claims dependent thereon (Remarks, page 9-10).
In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). Mukunda teaches a method of treating Tourette syndrome (TS) in human with a formulation comprising cannabis compound (e.g. CBD). Kumar teaches lyophilized CBD orally disintegrating tablet comprising gelatin and mannitol that rapidly disintegrates in mouth. It would have been prima facie obvious to one of ordinary skilled in the art before the effective filing date of the instant invention to incorporate the rapidly disintegrating CBD formulation taught by Kumar for method of treating Tourette syndrome as taught by Mukunda and reasonably expect the rapidly infusing composition comprising CBD would provide fast action of CBD for treating Tourette syndrome
Applicant argues Kumar composition comprises "an emulsifying agent or oleaginous vehicle in a concentration ranging from 0.1 to 20%" (Remarks, page 10).
RESPONSE: Although Kumar teaches emulsifier in the process of preparing cannabidiol suspension, emulsifier is not a required active agent responsible for the therapeutic effect in the final orally disintegrating tablet. “omission of an element and its function is obvious if the function of the element is not desired or required”. See MPEP 2144.04 II, Ex parte Wu, 10 USPQ 2031 (Bd. Pat. App. & Inter. 1989). In instant case, a skilled artisan would have known formulation development involves selection or omission of different excipient. Modifying Kumar’s formulation/ excluding emulsifier is considered as routine formulation optimization and does not render the claimed subject matter non-obvious. Instant specification does not provide any evidence that instant composition free of emulsifiers exhibit unexpected/super dissolution profile and/or efficacy for treating Tourette syndrome compared with composition comprising emulsifiers. Thus, the invention as a whole is prima facie obvious over Mukunda in view of Kumar in absence of evidence to the contrary.
Claims 1, 3-4, 6, 11-22, 39-40 are rejected under 35 U.S.C. 103 as being unpatentable over Mukunda et al. (WO 2020237247 A1), in view of Kumar et al. (WO2021028943A1), Grother et al. (WO 2022/074127 A2) and Novotny et al.(Frontiers in Neurology, 2018, 9:139, doi: 10.3389/fneur.2018.00139, Tourette Syndrome: A Mini-Review).
The collective teachings of Mukunda, Kumar and Novotny are elaborated in preceding 103 rejection and applied as before. Mukunda teaches a method of treating Tourette syndrome (TS) in human with a formulation comprising cannabis compound (e.g. CBD). Kumar teaches CBD orally disintegrating tablet comprising mannitol and fish gelatin that rapidly disintegrates in mouth. Kumar is silent about bovine gelatin and sucralose/acesulfame-K.
Grother teaches freeze-dried, oral disintegrating form comprising active ingredient (e.g. epinephrine), 10-40 wt. % matrix former (e. g. bovine gelatin, fish gelatin), and 10-40 wt. % structure former( e.g. mannitol) (See page 63, claims 1-10), Grother teaches the matrix former is bovine gelatin, fish gelatin etc. (See page 21, Table 1; Fig 30, claim 7-8) and the structure former is mannitol (See page 10, [0101]; page 21, Table 1; claim 10, etc.). Grother teaches the dosage form can also include coloring agents, flavoring agents, and sweeteners, wherein suitable coloring agents include yellow iron oxides and FD&C dyes, flavoring agents include lemon etc., suitable sweeteners include sucralose and acesulfame K (See page 11, [0102]-[0103], claims 16-17) (which reads on instant claims 14-16). Grother teaches embodiments comprising bovine gelatin, mannitol and sucralose (See Fig 27B, etc.).
Grother teaches the oral dosage form is a freeze dried (i.e. lyophilized), oral dispersible or disintegrating dosage form with disintegration time less than 10 seconds suitable for sublingual delivery (See [0095], [0099] [0179])(which reads on instant claim 3) . Grother teaches embodiments micronized with D50 of 10-40 microns (See page 15, [0122]; page 173, Fig. 76) (which reads on instant claim 12). Grother teaches treating a patient by placing the dosage form in the oral cavity’s buccal region (See page 3, [0011]; page 64 claims 19-20)(which reads on instant claim 17). Grother collectively teaches bovine gelatin in combination of mannitol and other inactive ingredients that could be used in freeze-dried orally disintegrating dosage form.
It would have been prima facie obvious to one of ordinary skilled in the art before the effective filing date of the instant invention to incorporate bovine gelatin in combination of mannitol taught by Grother into the rapidly disintegrating CBD formulation taught by Kumar for method of treating Tourette syndrome as taught by Mukunda, together with experimentation/ optimization based on the general knowledge of pharmaceutical composition(e.g. orally disintegrating dosage form). The skilled artisan would be motivated to do so because rapidly disintegrating dosage form is commonly known to provide advantages over conventional dosage form, e.g. rapid disintegration, rapid onset of action, etc. The skilled artisan would reasonably expect the rapidly infusing composition comprising CBD would provide fast action of CBD for treating Tourette syndrome (TS).
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 experimentation/ optimization based on the general knowledge of pharmaceutical composition(e.g. orally disintegrating dosage form) and Tourette syndrome treatment (e.g. symptoms, treatment outcome, etc.) as taught by Novotny. 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 Argument
Applicant argues against each reference on the record and alleged Mukunda, Kumar, Grother, and Novotny, alone or in combination, fail to teach, show, suggest, or otherwise render obvious claim 1 and claims dependent thereon.
RESPONSE: Again, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). Grother teaches freeze dried oral dispersible or disintegrating dosage form comprising bovine gelatin, mannitol and sucralose with disintegration time less than 10 seconds suitable for sublingual delivery. It would have been prima facie obvious to one of ordinary skilled in the art before the effective filing date of the instant invention to incorporate bovine gelatin in combination of mannitol taught by Grother into the rapidly disintegrating CBD formulation taught by Kumar for method of treating Tourette syndrome as taught by Mukunda,
Applicant relies on Seager’s teaching and argues CBD is a highly lipophilic and water-insoluble compound. Under Seager's teaching, a person of ordinary skill in the art would therefore expect CBD incorporated into a freeze dried orally disintegrating dosage form, such as the freeze-dried oral dispersible dosage forms described by Grother, to disperse in saliva and be swallowed rather than absorbed through the oral mucosa(Remarks, page 13).
RESPONSE: Applicant’s argument is fully considered, but NOT persuasive. Consistent with Kumar and Grother, Seager teaches Zydis fast-dissolving dosage form comprising gelatin and mannitol is ideal for patients including geriatrics and paediatrics and for those people who have difficulty swallowing. Seager also teaches some drugs are absorbed from the mouth, pharynx and oesophagus as the saliva passes down into the stomach. A skilled artisan would know buccal mucosa is part of oral cavity and oral disintegrating tablet could be administered by oral mucosa/ buccal mucosa. Both Kumar and Grother teach sublingual administration of lyophilized tablet that is considered as being delivered through oral mucosa. A skilled artisan would reasonably expect modified Kumar composition comprising mannitol and bovine gelatin capable of absorption through mucosa, if instant claimed CBD composition is capable of absorption through the oral mucosa.
More importantly, instant specification does not disclose any assay wherein instant claimed CBD composition is administered to a subject and absorbed through the oral mucosa. Instant specification does not disclose pharmacokinetic profile of instant CBD composition via mucosa and efficacy for treating Tourette syndrome in a subject. The mere recitation of mucosa absorption does not distinguish instant application over the combined teaching of prior art wherein Kumar and Grother teach sublingual administration of lyophilized tablet that is considered as being delivered through mucosa.
Conclusion
No claims are allowed.
THIS ACTION IS MADE FINAL. 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
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