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
Applicant’s amendment filed on 25 June 2025 is entered. Claim 1 is amended and claims 4-6, 8, and 10 are cancelled. Claims 1-3, 7, 9, and 11-17 are pending.
Domestic Benefit
Acknowledgment is made of Applicant’s claim for the benefit of the filing date of 62970721 filed 06 February 2020, 62975223 filed 12 February 2020, and PCT/IB2021/050893 filed 04 February 2021 of which the present application is a continuation-in-part. The effective filing date is 06 February 2020.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 21 March 2024 is being considered by the examiner.
Election/Restrictions
Applicant’s election without traverse of Group I, claims 1-3, 7, 9, and 11-14, in the reply filed on 25 June 2025 is acknowledged. Applicant’s election of Autism spectrum disorder; endocannabinoid receptors as the element of the endocannabinoid system; Cannabinoid type 1 (CB1) receptors that the at least one microorganism modulates; and the compound, N-palmitoylethanolamide (PEA), is acknowledged.
Claims 15-17 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 25 June 2025.
Claims 1-3, 7, 9, and 11-14 are under examination.
Claim Objections
Claims 1, 7, and 13 are objected to because of the following informalities:
In claim 1, the term “combination thereof” at the end of (ii) should be pluralized. The term “Parkinson disease” should be “Parkinson’s disease”. Commas should be added after the terms “inflammation” in line 5, “Bacteroides” in line 8, and “N-oleoyl ethanolamine (OEA)” in line 12.
In claim 7, a comma should be added after the term “diacylglycerol (DAG) lipases”. Additionally, the Markush group is in improper form because it is terminated with the conjunction “or”. Standard practice for reciting Markush groups has the terminal conjunction be “and”, rather than “or” as the claim presently recites to emphasize that the listed members are all part of the “group” of alternatives to be selected from. It is suggested to amend the Markush group to change the terminal conjunction “or” to “and” to obviate this objection.
Claim 13 is convoluted. It is suggested to amend the claim to recite “The method of claim 1, comprising administering the at least one microorganism and/or prebiotic, and the at least one compound multiple times.”
Appropriate correction is required.
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.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
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 of carrying out his invention.
Claims 1-3, 7, 9, and 11-14 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 written description requirement. The claims contain subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventors, at the time the application was filed, had possession of the claimed invention.
Claim 1 recites a method of treating a condition and/or symptom of selected from the group consisting of migraine, fibromyalgia, post-traumatic stress disorders, affective disorders, multiple sclerosis, Parkinson’s disease, autism spectrum disorder, clinical deficiency of an endocannabinoid, visceral pain, inflammation, and combinations thereof in an animal, the method comprising administering to said animal: (i) a therapeutically effective amount of at least one microorganism comprising a strain selected from the group consisting of Lactobacillus, Bifidobacterium, Prevotella, Bacteroides and combinations thereof, and/or of a prebiotic thereof, as well as a therapeutically effective amount of at least one compound selected from the group consisting of a cannabinoid, 2-linoleoyl-glycerol (2-Lino-Gl), 2-palmitoyl-glycerol (2-Palm-Gl), N-palmitoylethanolamide (PEA), N-oleoyl ethanolamine (OEA), and combinations thereof.
The broadest reasonable interpretation of the method includes the administration of a therapeutically effective amount of any prebiotic compound. The specification defines a prebiotic as “a substrate that is selectively utilized by particular microorganisms conferring a health benefit” (specification [0010]). The BRI of this definition includes compounds such as water, minerals, and vitamins because these compounds are utilized by microorganisms. As disclosed, the term prebiotic covers a broad scope of compounds.
However, the specification lacks sufficient written description for the full genus of prebiotics, as well as the therapeutically effective amounts of said prebiotics necessary to treat the elected condition of autism spectrum disorder.
MPEP §2163.02 states “[a]n applicant shows that the inventor was in possession of the claimed invention by describing the claimed invention with all of its limitations using such descriptive means as words, structures, figures, diagrams, and formulas that fully set forth the claimed invention. Lockwood v. Am. Airlines, Inc., 107 F.3d 1565, 1572, 41 USPQ2d 1961, 1966 (Fed. Cir. 1997). Possession may be shown in a variety of ways including description of an actual reduction to practice, or by showing that the invention was "ready for patenting" such as by the disclosure of drawings or structural chemical formulas that show that the invention was complete, or by describing distinguishing identifying characteristics sufficient to show that the inventor was in possession of the claimed invention.”
The instant disclosure lacks any working examples describing therapeutically effective amounts of prebiotics to treat autism spectrum disorder, nor does the disclosure provide any list of prebiotic compounds applicable to the instant invention. The specification also lacks sufficient description of any necessary structures or features of a prebiotic to be therapeutically effective at treating autism spectrum disorder. The instant disclosure only provides a broad suggestion, without any description, guidance, or direction, that a therapeutically effective amount of a prebiotic may be administered to confer the benefit of treating autism spectrum disorder.
Reflecting the state of prior art, Adams et al. (US 20200061127 A1, published 27 February 2020, effectively filed 11 November 2016) discloses a method of treating autism spectrum disorder comprising administering a pharmaceutical composition comprising a fecal microbe preparation (Adams [0199]), wherein the pharmaceutical composition comprises microorganisms Lactobacillus, Bifidobacterium, Bacteroides, and Prevotella (Adams [0220]-[0221]) and prebiotic compounds polyols, fructooligosaccharides (FOSs), oligofructoses, inulins, galactooligosaccharides (GOSs), xylooligosaccharides (XOSs), polydextroses, monosaccharides, tagatose, and/or mannooligosaccharides. (Adams [0214]). Adams teaches that these prebiotics are supplemental nutrients within their composition ([0214]), but does not disclose any therapeutically effective amount of these prebiotics necessary for treating autism spectrum disorder, nor does Adams disclose a structure-function relationship of these prebiotics for treating autism spectrum disorder.
Gioacchini et al. (Host-probiotic interaction: new insight into the role of the endocannabinoid system by in vivo and ex vivo approaches, Scientific Reports 7:1261, 28 April 2017) 7 teaches a probiotic composition called VSL#3 comprising probiotics Lactobacillus and Bifidobacterium species (Gioacchini pg. 1 para. 4) increases the expression of the cnr1 gene both in vivo and ex vivo (Gioacchini Figs. 2-3 and 5-6 and pg. 3 para. 1). The gene cnr1 encodes endocannabinoid receptor 1 (CB1 or CBR1) (Gioacchini pg. 1 para. 1), which when activated plays a critical role in the improvement of autism spectrum disorder behavior and synaptic dysfunction, according to the Abstract of Wang et al. (Activation of CB1R alleviates autism spectrum disorder-like behavior and synaptic impairments, Life Sciences 377 (2025) 123797). However, despite Gioacchini’s teaching of a probiotic microorganism containing composition sufficient to increase expression of a critical receptor for the treatment of autism spectrum disorder, nowhere does Gioacchini disclose any prebiotic compounds which are utilized by these probiotic microorganisms, much less a therapeutically effective amount of such prebiotics.
Shaaban et al. (The role of probiotics in children with autism spectrum disorder: A prospective, open-label study, Nutritional Neuroscience, 2018, vol. 21, no. 9) teaches supplementation of autistic children with compositions comprising probiotics microorganisms Lactobacillus acidophilus, Lactobacillus rhamnosus, and Bifidobacterium longum was able to confer significant improvements in the severity of autism (Shaaban abstract). However, Shaaban also does not disclose any prebiotic compounds suitable for treating autism, but does recommend further studies to investigate prebiotic supplementation with probiotic microorganisms for autistic children (Shaaban pg. 681 para. 3). This statement suggests that few if any studies have been conducted which indicate the effect of administering prebiotics to treat autism spectrum disorder, either with probiotic microorganisms or on their own.
Lacking sufficient prior art knowledge of the structure-function relationship for the claimed genus of prebiotics, the specification does not provide sufficient description of the genus such that one of ordinary skill in the art would be able to reasonably predict its entire scope. Thus, one of ordinary skill in the art would conclude that Applicant was not in possession of the entire genus of prebiotics as claimed.
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.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1-3, 7, 9, and 11-14 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, 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.
Claim 1 recites a method of treating a condition and/or a symptom selected from the group consisting of migraine, fibromyalgia, post-traumatic stress disorders, affective disorders, multiple sclerosis, Parkinson’s disease, autism spectrum disorder, clinical deficiency of an endocannabinoid, visceral pain, inflammation, and combinations thereof. The contents of the Markush group are all conditions, diseases, or disorders, but they are not symptoms themselves. It is unclear how the alternatives within the Markush group are classified as symptoms.
Claim 1 also recites administering a therapeutically effective amount of at least one microorganism comprising a strain selected from the group consisting of Lactobacillus, Bifidobacterium, Prevotella, Bacteroides and combinations thereof and/or of a prebiotic thereof. The term “prebiotic” is broadly defined within the specification as a substrate that is selectively utilized by particular microorganisms conferring a health benefit (specification [0010]); however, the term “prebiotic thereof” seems to indicate that the prebiotic is now limited to a substrate that the at least one microorganism recited immediately prior is able to utilize. Thus, it is unclear if the “prebiotic” is limited to a prebiotic which is utilized by the at least one microorganism recited immediately before the term, or if the claimed prebiotic is any substrate that is selectively utilized by any microorganism conferring a health benefit which is commensurate in scope with the definition recited in the specification.
Claims 2-3, 7, 9, and 11-14 are dependent on claim 1, and so are indefinite for the same reasons.
Claims 2-3 recite the limitation "said at least one element of said endocannabinoid system". There is insufficient antecedent basis for this limitation in the claims.
Claim 11 recites administering said at least one microorganism comprises feeding the animal a food comprising a therapeutically effective amount of said microorganism and/or said prebiotic. The BRI of the phrase “a food comprising a therapeutically effective amount of said microorganism and/or said prebiotic” includes a food comprising the prebiotic alone without the microorganism. Thus, it is unclear how the limitation “administering said at least one microorganism comprising feeding said animal a food” can be accomplished in the event that the food only comprises a prebiotic without a microorganism.
Claim 14 recites the at least one microorganism and/or prebiotic, and the at least one compound are provided as a kit. It is unclear if claim 14 recites an additional active step to the method of claim 1, thereby requiring that the microorganism(s), prebiotic(s), and compound(s) to be actively provided to the animal as a kit, or if claim 14 merely limits the microorganism(s), prebiotic(s), and compound(s) to be packaged in a kit.
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.
Claims 1, 9 and 11-14 are rejected under 35 U.S.C. 103 as being unpatentable over Adams et al. (US 20200061127 A1, published 27 February 2020, effectively filed 11 November 2016) in view of Cristiano et al. (Palmitoylethanolamide counteracts autistic-like behaviours in BTBR T+tf/J mice: Contribution of central and peripheral mechanisms, Brain, Behavior, and Immunity 74 (2018) 166–175).
Regarding claim 1, Adams teaches a method of treating autism spectrum disorder comprising administering a pharmaceutical composition comprising a fecal microbe preparation (Adams [0199]), wherein the pharmaceutical composition comprises microorganisms Lactobacillus, Bifidobacterium, Bacteroides, and Prevotella (Adams [0220]-[0221]) and prebiotics (Adams [0214]).
Adams does not teach administration of N-palmitoylethanolamide (PEA) to treat autism spectrum disorder.
Cristiano teaches that administration of PEA to BTBR mice reverted the autistic behavioral phenotype of BTBR autistic-model mice, restored the hippocampal brain-derived neurotrophic factor (BDNF) signaling pathway, and improved mitochondrial dysfunction, which are all pathological aspects consistently associated with autism spectrum disorder, thereby concluding that PEA demonstrated therapeutic potential in limiting symptoms of autism spectrum disorder (Cristiano abstract).
It would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date of the present invention to combine Adams’ composition (comprising Lactobacillus, Bifidobacterium, Bacteroides, Prevotella, and prebiotics) with Cristiano’s PEA to form a new composition for the same purpose, to be administered to a subject in need thereof to treat autism spectrum disorder.
MPEP §2144.06(I) states "[i]t is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art."
Adams taught that administering a composition comprising Lactobacillus, Bifidobacterium, Bacteroides, Prevotella, and prebiotics to a subject could treat autism spectrum disorder. Likewise, Cristiano taught that administering PEA to BTBR mice (an autism murine model) alleviated symptoms of autism spectrum disorder. Thus, one of ordinary skill in the art would have reasonably concluded that combining the autism spectrum disorder treatments of Adams and Cristiano would predictably result in the treatment of autism spectrum disorder.
Regarding claim 9, Cristiano teaches that PEA is able to modulate the gut-brain axis (Cristiano abstract), and thus is a neuromodulator in the enteric system (gut).
Regarding claim 11, Adams teaches their pharmaceutical composition is in the form of a food (Adams [0207]-[0208]).
Regarding claim 12, neither Adams nor Cristiano teach administering the Lactobacillus, Bifidobacterium, Bacteroides, Prevotella and prebiotic composition prior to administering the PEA composition, nor do Adams and Cristiano teach administering the Lactobacillus, Bifidobacterium, Bacteroides, Prevotella and prebiotic composition simultaneously with the PEA composition.
However, it would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date of the present invention that the order of administration of each component in the composition comprising microorganisms Lactobacillus, Bifidobacterium, Bacteroides, and Prevotella, prebiotics, and the compound PEA as taught by Adams in view of Cristiano would be either simultaneous, when all of the components are mixed together into one composition, or subsequent, when Adam’s composition is packaged in a separate container from Cristiano’s compound, PEA, and that Adam’s composition is administered prior to Cristiano’s PEA stored in a second container in a kit.
Regarding claim 13, Adams teaches the composition is administered multiple times (Adams [0199]-[0204]).
Regarding claim 14, Adams teaches their pharmaceutical composition is provided as part of a kit (Adams [0256]).
Claim 2 is rejected under 35 U.S.C. 103 as being unpatentable over Adams in view of Cristiano as applied to claims 1, 9, and 11-14 above, and further in view of Gioacchini et al. (Host-probiotic interaction: new insight into the role of the endocannabinoid system by in vivo and ex vivo approaches, Scientific Reports 7:1261, 28 April 2017) and Borelli et al. (Palmitoylethanolamide, a naturally occurring lipid, is an orally effective intestinal anti-inflammatory agent, British Journal of Pharmacology (2015), 172, 142–158).
It is noted that the instant specification defines the term “element of the endocannabinoid system” to be an endocannabinoid, a cannabinoid receptor, or an enzyme responsible for the synthesis or degradation of an endocannabinoid (instant specification [0022]).
Neither Adams nor Cristiano teach that Lactobacillus, Bifidobacterium, Bacteroides, and Prevotella modulate an element of the endocannabinoid system, which is the same element that PEA modulates.
Gioacchini teaches a probiotic composition called VSL#3, which comprises Lactobacillus and Bifidobacterium species (Gioacchini pg. 1 para. 4), increases the expression of the cnr1 gene both in vivo and ex vivo (Gioacchini Figs. 2-3 and 5-6 and pg. 3 para. 1). The gene cnr1 encodes endocannabinoid receptor 1 (Cnr1 or CB1 as recited in instant claim 7) (Gioacchini pg. 1 para. 1).
Gioacchini does not teach that PEA is able to modulate expression of endocannabinoid receptor 1 (CB1), the endocannabinoid element that the probiotic composition comprising Lactobacillus and Bifidobacterium species modulates.
Borelli teaches that PEA is able to act via several targets, including CB1 receptors (Borelli abstract), and that PEA is able to up-regulate mRNA expression of the CB1 receptor (Borelli Fig. 7).
Therefore, it would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date of the present invention to use the probiotic Lactobacillus and Bifidobacterium species and the PEA components within the composition of Adams modified by Cristiano to modulate the same element of the endocannabinoid system, namely CB1, because Gioacchini taught a probiotic composition comprising probiotic Lactobacillus and Bifidobacterium microorganisms modulate CB1 receptors and Borelli taught that PEA modulates those same CB1 receptors.
Claims 3 and 7 are rejected under 35 U.S.C. 103 as being unpatentable over Adams in view of Cristiano as applied to claims 1, 9, and 11-14 above, and further in view of Gioacchini et al. (Host-probiotic interaction: new insight into the role of the endocannabinoid system by in vivo and ex vivo approaches, Scientific Reports 7:1261, 28 April 2017).
Cristiano teaches that PEA treats autism by activating endocannabinoid receptor peroxisome-proliferator activated receptor alpha (PPAR-alpha), an endocannabinoid receptor (Cristiano Abstract and pg. 169 sec. 3.2 para. 1).
Adams and Cristiano do not teach that Lactobacillus, Bifidobacterium, Bacteroides, Prevotella modulate an element of the endocannabinoid system, which is different from the PPAR-alpha element that PEA modulates.
However, Gioacchini teaches a probiotic composition called VSL#3, which comprises Lactobacillus and Bifidobacterium species (Gioacchini pg. 1 para. 4), increases the expression of the cnr1 gene both in vivo and ex vivo (Gioacchini Figs. 2-3 and 5-6 and pg. 3 para. 1). The gene cnr1 encodes endocannabinoid receptor 1 (Cnr1 or CB1 as recited in instant claim 7) (Gioacchini pg. 1 para. 1). The specification defines the term “element of the endocannabinoid system” to be an endocannabinoid, a cannabinoid receptor, or an enzyme responsible for the synthesis or degradation of an endocannabinoid (instant specification [0022]).
It would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date of the present invention to use the Lactobacillus and Bifidobacterium in Adams’ composition to modulate the Cnr1 or CB1 element of the endocannabinoid system, and to use Cristiano’s PEA to modulate the PPAR-alpha endocannabinoid system. It would have been immediately apparent to one of ordinary skill in the art that the microorganisms taught by Adams could modulate CB1, which is a different element of the endocannabinoid system than that of the PPAR-alpha modulated by Cristiano’s PEA.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ALEXANDER M DURYEE whose telephone number is (571)272-9377. The examiner can normally be reached Monday - Friday 9:00 am - 5:00 pm.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Louise Humphrey can be reached on (571)-272-5543. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/LOUISE W HUMPHREY/Supervisory Patent Examiner, Art Unit 1657
/Alexander M Duryee/Examiner, Art Unit 1657