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 .
Claims status
Claims 1-7 are pending in the application and have been examined on the merits.
Priority
The present application claims status as a continuation of International Patent Application No. PCT/CN2023/119447, filed on 09/18/2023, which claims the priority of Chinese Patent Application No. CN202211135180.5, filed on 09/19/2022. Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Claim Objections
Claim 1 is objected to because of the following informalities: The claim recites the symbol “=” in line 5. It is understood this symbol is used to denote that the two bacterial strain numbers are equivalent. Please amend “=” to “or”. Appropriate correction is required.
Claim 4 is objected to because of the following informalities: The claim recites “wherein the Prevotella copri is formulated into a pharmaceutical preparation, the pharmaceutical preparation comprises…” in line 2. For clarity, this phrase can be amended to recite “wherein the Prevotella copri is formulated into a pharmaceutical preparation, wherein the pharmaceutical preparation comprises…”. Appropriate correction is required.
Claim 5 is objected to because of the following informalities: For clarity, the limitation, “wherein a dosage form of the pharmaceutical preparation comprises any one of pharmacologically acceptable dosage forms” can be amended to recite “wherein the pharmaceutical preparation comprises a pharmacologically acceptable dosage form.” without changing the meaning of the claim. Appropriate correction is required.
Claim 6 is objected to because of the following informalities: For clarity, please amend the phrase “any one or more of pharmaceutically acceptable excipients” in line 2 by removing “of” (i.e., “any one or more [[of]]pharmaceutically acceptable excipients”). Appropriate correction is required.
Claim Interpretation
Claim 1 recites a strain number of the Prevotella copri that is “Japan Collection of Microorganisms (JCM) 13464” or “Deutsche Sammlung von Mikroorganismen und Zelkulturen (DSM) 18205”. In view of Huang et al. (Huang, et al. Cultivation of the gut bacterium Prevotella copri DSM 18205T using glucose and xylose as carbon sources. Microbiologyopen. 2021 Jun;10(3):e1213; cited on Form 892), DSM18205 is a type strain of Prevotella copri (see Abstract, “DSM18205T”) which can be purchased from the German Collection of Microorganisms and Cell cultures (DSMZ) (Braunschweig, Germany) (see pg. 2, col. 2, para. 2).
Therefore, it is apparent in view of the prior art that DSM 18205, which is also known as JCM 13464, is a known type strain that is readily available to the public. For these reasons, the enablement requirements under 35 U.S.C. 112, first paragraph, are considered to have been met regarding the deposit numbers recited in the claim.
Claim Rejections - 35 USC § 112(b)
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 1-7 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 “An application method of Prevotella copri, comprising applying the Prevotella copri in preventing and treating attention-deficit hyperactivity disorder (ADHD); wherein the Prevotella copri is applied in an effective therapeutic amount to achieve treating the ADHD…” which renders the claim indefinite for the following reasons.
First, it is unclear if the claim is reciting a general use of the Prevotella (“applying”) or an administration step. This is rendered further unclear, because, even though the claim recites a treatment, it does not identify a recipient for said treatment (e.g., “a subject in need”, “human”, “mammal”, “child”, etc.). Therefore, it is not clear whether the claim requires a recipient, let alone which recipients are included or excluded by the scope of the claim.
Second, the plain meaning of the term “applying”, in the context of physically applying something, would refer to placing or disposing the recited element on a surface. Therefore, in the context of an administration, “applying” could be interpreted as a topical administration. However, in view of the specification, the primary route of administration appears to be gavage (see pg. 3, para. [0017]; pg. 8, para. [0047]), and there is no mention of any topical administration. Furthermore, Prevotella copri’s activities in the body are described as affecting the gut and gut-brain axis (see pg. 4, para. [0019]), which raises doubt that the P. copri is intended for external use. Moreover, dependent claim 7 recites gavage as a further limitation, which must be within the scope of claim 1. Hence, the use of “applying” in lieu of “administering” leads to confusion regarding the scope of the method.
Finally, the claim recites “applying the Prevotella copri in preventing and treating… (ADHD)… in an effective amount to achieve treating the ADHD”. Here, “preventing” and “treating” have different scopes but are not recited in the alternative. Therefore, it is unclear if the claim limits the patient population to those who have ADHD (i.e., in a method of treating and preventing further prevalence) or if said population includes those who have not yet developed ADHD (i.e., in a method of preventing or treating). Furthermore, the claim recites, “to achieve treating the ADHD”, but does not recite ‘to achieve preventing the ADHD’ which adds further uncertainty as to the intended scope of the claim.
In the interest of compact prosecution, the examiner sets forth the broadest reasonable interpretation (BRI) of the claim based, in part, on the following written support:
In view of the specification, the background of the invention discusses ADHD in humans, particularly children (see pgs. 1-2; paras. [0003]-[0007]) and further the role of Prevotella copri as a probiotic in the human body, particularly in infants (see pg. 2, para. [0008]). However, the remainder of the specification, including Applicant’s embodiments, does not recite any recipient of the treatment method (e.g., subject, individual, human, child, infant, mammal), other than “rats”, specifically, “spontaneously hypertensive rats (SHR)” which were used in the inventors’ experiments (see, e.g., pg. 7, para. [0046]).
In view of the prior art of Sagvolden et al. (The spontaneously hypertensive rat model of ADHD--the importance of selecting the appropriate reference strain. Neuropharmacology. 2009 Dec;57(7-8):619-26; cited on Form 892), the spontaneously hypertensive rat (SHR) appears to be commonly used in the art as a model for ADHD in humans (see pg. 3, para. 2; pg. 9, para. 1) with certain strains constituting the best validated animal model of ADHD combined subtype (ADHD-C) (see Abstract). It should also be noted that while animal models for this condition exist, ADHD appears to be widely regarded as a disorder in humans, not other animals.
In view of the foregoing, a person of ordinary skill would reasonably infer from Applicant’s disclosure that the claimed method of prevention and treatment is intended for humans. This is because the specification clearly identifies ADHD in humans as being the problem to be solved, and all experiments are directed to animal models commonly used to predict therapeutic outcomes in humans, specifically ADHD.
Therefore, the claim is interpreted as follows:
“A method of preventing or treating attention-deficit hyperactivity disorder (ADHD) in a human, the method comprising administering a Prevotella copri strain to the human in an effective therapeutic amount to prevent or treat ADHD, wherein the Prevotella copri strain is Japan Collection of Microorganisms (JCM) 13464 or Deutsche Sammulung von Microorganismen und Zelkulturen (DSM) 18205.”
For the sake of applying prior art, the subject is broadly interpreted to be any human. This is because the claim recites a method of preventing, which does not require the human to already have ADHD.
Suggestion to obviate the rejection: Applicant may, for example, amend the claim to recite the examiner’s interpretation above. However, Applicant is advised that each of the dependent claims must be amended accordingly in order to provide proper antecedent basis.
Claim 7 recites the limitation "wherein an administration method for the Prevotella copri comprises gavage administration”, which renders the claim indefinite because it is unclear whether it refers to the step of “applying” recited in claim 1 or to a separate method step. Furthermore, the claim recites “The application method… wherein an administration method for the Prevotella copri” appears to introduce a second method without clearly delineating its relation to the first method.
Suggestion to obviate the rejection: Provided that Applicant elects to amend claim 1 according to the examiner’s suggestion above, the further limitation of claim 7 may be amended to recite, for example, “wherein the administering of the Prevotella copri comprises gavage.”
For the sake of applying prior art, the claim is interpreted accordingly.
Claims 2-7 are also rejected for depending from claim 1 and failing to rectify the indefiniteness of the claim from which they depend.
Claim Rejections - 35 USC § 103
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
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.
Claim(s) 1-6 is/are rejected under 35 U.S.C. 103 as being unpatentable over Vuillermin et al. (US 2021/0177904 A1; cited on Form 892), hereafter, “Vuillermin”.
Regarding claim 1, Vuillermin teaches a method for minimizing the likelihood of development of a problem behavior in an individual including administering a composition including bacteria to an individual in whom the likelihood of development of a behavior is to be minimized, wherein the composition includes an effective amount of Prevotella, thereby minimizing the likelihood of development of the behavior in the individual, wherein the composition is administered to the individual before the individual is 3 years old (see claim 1). Vuillermin teaches the method, wherein the composition includes an effective amount of Prevotella copri (see claim 15).
Vuillermin teaches that the composition formulated for human consumption comprises a strain of bacteria deposited as DSM number 18205 (JCM13464) with Leibniz Institute DSMZ-German Collection of Microorganisms and Cell Cultures (see pg. 7, para. [0110]). Vuillermin teaches that the Prevotella copri may be produced by culturing a strain of bacteria deposited as DSM number 18205 described above (see pg. 8, para. [0127]). Therefore, Vuillermin teaches the method comprising the same type-strain recited in the instant claim.
Regarding the limitation, “to prevent or treat ADHD”, as discussed under 35 U.S.C. 112(b), the claim is interpreted to encompass administering the Prevotella copri strain to any human. This is because a method for “preventing” ADHD does not require the subject to have ADHD.
Therefore, Vuillermin teaches a method comprising administering a Prevotella copri DSM 18205 strain to a human.
Vuillermin does not teach an “effective therapeutic amount to prevent or treat ADHD”.
However, Vuillermin teaches the individual may be administered Prevotella to provide 1x106 to 1x1011 colony forming units (CFUs) of Prevotella per day to the individual (see pg. 6, para. [0092]).
In view of the instant specification (see pg. 3, para. [0013]) and the instant claims (see dependent claim 3), the effective therapeutic amount of the Prevotella copri includes 200 microliters (µL) at a concentration of 2.8x108 colony-forming units per milliliter (CFU/mL). Therefore, an effective therapeutic amount of the instant claim includes 5.6x107 CFUs of the bacterial strain, which falls within the range taught by Vuillermin.
"[A] prior art reference that discloses a range encompassing a somewhat narrower claimed range is sufficient to establish a prima facie case of obviousness." In re Peterson, 315 F.3d 1325, 1330, 65 USPQ2d 1379, 1382-83 (Fed. Cir. 2003). Further, there is no evidence in Applicant’s disclosure to support that the “effective therapeutic amount” of 5.6x107 CFUs was critical. See MPEP 2144.05(II)(A) which states:
Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. “[W]here 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.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). (Emphasis added)
See also MPEP 2144.05(III)(A) which states:
"The law is replete with cases in which the difference between the claimed invention and the prior art is some range or other variable within the claims. . . . In such a situation, the applicant must show that the particular range is critical, generally by showing that the claimed range achieves unexpected results relative to the prior art range." In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). (Emphasis added)
In the instant case, there is no evidence in Applicant’s disclosure that the claimed “effective therapeutic amount” was critical to the invention, including the amount recited in claim 3, which effectively falls within the range taught by Vuillermin.
It should also be noted that the volume recited in dependent claim 3 (200 µL) does not affect this inquiry, because the present claim does not require the bacterium to be administered as a liquid preparation (see dependent claim 4). Vuillermin teaches that the Prevotella is provided orally to the individual in the form of a tablet (see pg. 6, para. [0096]), which meets the limitation of a “solid preparation” recited in claim 4, which is necessarily within the scope of the present claim. Therefore, Vuillermin teaches an effective amount of P. copri in CFUs which, in view of Applicant’s disclosure, includes an amount that is effective to prevent or treat ADHD.
Therefore, it would have been obvious to have administered 5.6x107 CFUs of the Prevotella copri DSM 18205, which meets the limitation of an “effective therapeutic amount”.
Regarding claim 2, the further limitation, “wherein the ADHD comprises ADHD caused by abnormal brain function development”, the method of preventing does not require the subject to have ADHD, as discussed above. As discussed under 35 U.S.C. 112(b), the claim is interpreted to encompass administering the Prevotella copri strain to any human for preventing ADHD, including subjects who do not display any signs of the disorder. Similarly, the claim does not specify whether the human needs to be identified (i.e., diagnosed) with the abnormal brain function prior to the step of administering, and it is broadly interpreted that the method of “preventing” includes humans who have not (yet) been identified as having the abnormal brain function. Therefore, the further limitation of the claim does not amount to any manipulative difference in the method.
Regarding claim 3, Vuillermin teaches the individual may be administered Prevotella to provide 1x106 to 1x1011 colony forming units (CFUs) of Prevotella per day to the individual (see pg. 6, para. [0092]). Therefore, an effective therapeutic amount of the instant claim includes 5.6x107 CFUs of the bacterial strain, which falls within the range taught by Vuillermin.
"[A] prior art reference that discloses a range encompassing a somewhat narrower claimed range is sufficient to establish a prima facie case of obviousness." In re Peterson, 315 F.3d 1325, 1330, 65 USPQ2d 1379, 1382-83 (Fed. Cir. 2003). As previously discussed, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical, and the applicant must show that the particular range is critical, generally by showing that the claimed range achieves unexpected results relative to the prior art range. See MPEP 2144.05(II)(A) and MPEP 2144.05(III)(A). In the instant case, there is no evidence in Applicant’s disclosure that the claimed “effective therapeutic amount” was critical to the invention, including the amount recited in claim 3, which effectively falls within the range taught by Vuillermin.
In view of the instant specification, the group of rats which received P. copri were administered 200 µL of P. copri solution at a concentration of 2x108-2x109 CFU/mL per day (see pg. 8, para. [0047]). Applicant’s disclosure does not provide any comparison of varying concentrations or volumes to demonstrate that the claimed volume of 200 µL or the claimed concentration of 2.8x108 CFU/mL was somehow critical to the claimed invention.
Therefore, Vuillermin provides a result-effective variable (in CFUs per day) which a person of ordinary skill could have used to arrive at an appropriate concentration and volume, which would have required no more than routine optimization. It is well within the ordinary skill in the art to determine a volume and concentration of a probiotic composition having already determined an effective dose in CFUs.
Regarding claim 4, Vuillermin teaches the composition “formulated for human consumption” comprising a strain of bacteria deposited as DSM number 18205 (see pg. 7, para. [0110]). Vuillermin teaches that a composition “formulated for human consumption” refers to a composition that contains excipients, diluents or carriers that are generally regarded as safe for consumption by humans (see pg. 2, para. [0032]). Hence, Vuillermin’s composition meets the limitation of a “pharmaceutical preparation”. Vuillermin teaches that the Prevotella is provided orally to the individual in the form of a tablet (see pg. 6, para. [0096]), which meets the limitation of a “solid preparation”.
Regarding claim 5, Vuillermin teaches that the composition includes an effective amount of Prevotella (see claim 1) in the form of a tablet (see pg. 6, para. [0096]) “formulated for human consumption” (see pg. 7, para. [0110]) which refers to a composition that contains excipients, diluents or carriers that are generally regarded as safe for consumption by humans and does not contain ingredients or components that are unsafe for human consumption (see pg. 2, para. [0032]). Therefore, Vuillermin teaches the pharmaceutical preparation comprises a “pharmacologically acceptable” dosage form.
Regarding claim 6, Vuillermin teaches the composition comprises pharmaceutically acceptable excipients, as discussed above.
Claim(s) 7 is/are rejected under 35 U.S.C. 103 as being unpatentable over Vuillermin as applied to claims 1-6 above, and further in view of Ross, et al. (Feasibility of fecal microbiota transplantation via oral gavage to safely alter gut microbiome composition in marmosets. Am J Primatol. 2020 Dec;82(12):e23196; cited on Form 892), hereafter, “Ross”.
Regarding claim 7, Vuillermin teaches that there is growing evidence that the gut microbiome is crucial for normal neurodevelopment via neuronal, hormonal and immunological signaling, and rodent studies demonstrate that disruptions to gut microbiota are associated with aberrant hypothalamic-pituitary-adrenal axis stress response, decreased expression of brain derived neurotrophic factor and impaired social behavior in germ-free mice (see pg. 1, para. [0003]).
Vuillermin does not teach the method wherein the administering of the Prevotella copri comprises gavage.
Ross teaches that the disruption of microbial communities within human hosts has been associated with infection, obesity, cognitive decline, cancer risk and frailty, suggesting that microbiome-targeted therapies may be an option for improving health and lifespan. The objectives of this study were to determine the feasibility of delivering fecal microbiota transplants (FMTs) to marmosets via oral gavage and to evaluate if alteration of the gut microbiome post-FMT could be achieved. Ross discloses that the FMT recipients did not experience any negative health outcomes over the course of the treatment, and FMT via oral gavage was safe to administer to young adults. See Abstract.
Ross discloses that while FMT has been conducted in humans via either lower (e.g., colonoscopy) or upper (e.g., capsule, suspension) gastrointestinal delivery, the oral route of administration was chosen for this study for several reasons. First, from a safety and ethics perspective, oral administration does not require surgical intervention, thus limiting the risk for adverse events in the animals. Second, rodent FMT has been traditionally conducted using oral gavage and was the basis of the design in this study. Finally, the researchers aimed to produce study findings that would be the most translatable to humans in the future, and oral FMT is likely more translatable to human use and does not require surgical intervention. See pg. 8, para. 2.
It would have been obvious at the time of filing for a person of ordinary skill in the art to have arrived at the claimed invention by combining the teachings of Vuillermin and Ross, because Ross teaches that oral gavage can effectively alter the gut microbiome without surgical intervention. One would have recognized that the general goals of administering a fecal bacterium, such as Prevotella, to the gastrointestinal tract of an individual are the same as when administering an FMT, i.e., to remedy disruptions to the gut microbiota in order to effect a disease outcome. One would have recognized that the administration of probiotics by oral gavage is well established in animal models and that Ross teaches these methods to be the most translatable to humans. As the effects of treatment taught by Vuillermin are disclosed as being a result of delivering Prevotella to the gut, a person of skill would have expected oral gavage to be a sufficient means for achieving this outcome. Therefore, the results of using oral gavage to administer the Prevotella strain would have been predictable and there would have been a reasonable expectation of success. Hence, the combination would have been readily apparent and deemed to be a mere (A) combining of prior art elements according to known methods to yield predictable results (see MPEP 2143(I): Rationales to support rejections under 35 U.S.C. 103).
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to DENNIS ARMATO whose telephone number is (703)756-5348. The examiner can normally be reached Mon-Fri 11:00am-7:30pm EST.
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, Melenie Gordon can be reached at (571) 272-8037. 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.
/DENNIS IGNATIUS ARMATO JR/Examiner, Art Unit 1651
/MELENIE L GORDON/Supervisory Patent Examiner, Art Unit 1651
Prosecution Insights