DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 9/19/2025 has been entered.
Claims 18-37 are pending and have been considered on the merits herein.
Applicants Declarations Attachments A and B (as part of the Patent inference No. 106,130) and the de Vos Declaration (attachment C) filed under 37 CFR 1.132 filed herein on 9/19/2025 have been entered and considered.
All arguments and amendments have been considered.
Interference
There are on-going court proceedings involving the Interference of parent application 14/443926, Interference No. 106,130. In light of the decision by the PTAB in Interference No. 106,130, regarding Kaplan (interfering party) and Cani (applicants) claims to benefit of priority applications, Kaplan was accorded the benefit date of February 28, 2013 (to US9173910) and applicants Cani (for examined claims in parent Application 14/443926) were accorded the benefit of date November 19, 2012 (to PCT/EP2012/073011) (see Appendix C, p. 25 of CAFC filed in parent 14443829 6/20/2025 and Exhibit A, p. 5-89, Exhibit B, p. 90-92 of Decision, applicants’ response filed on 8/9/2024 in the instant application). It should also be of record that the Decision filed on 8/9/2024 p. 44 indicates that the Everard “Keystone poster” is evidence of a reduction to practice of the method claimed as of March 6, 2012 (awarded to parent 1443829, i.e. Cani (applicants)).
In light of this decision the Everard poster is not prior art against the instant claims and applicants arguments regarding the Belzer reference, the rejection of Claim 18-21, 27 rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over the combination of Belzer (2012, IDS), Everard et al. (Keystone conference poster, March 6, 2012), Everard, 2011 (IDS) and Derrien et al. (Frontiers in Micro., 2011, IDS) is withdrawn.
Further in light of this evidence and decision, applicants are enabled for and receive this priority date for a method of treating obesity and diabetes, see applicants arguments filed 9/19/2025 p. 7-8, which states that “Drs. Cani, de Vos, Geurts and Everard discussed the data as described in Section 1 above, and concluded, “before February 29, 2012, that oral administration of Akkermansia reduced body weight gain and fat mass development in the mice relative to control mice. As losing weight is the main treatment for obesity, these results indicated that oral administration of Akkermansia contributes to the treatment of obesity.” (Attachment A, para. 27.) Further, “weight loss or prevention of weight gain in the DIO mouse model is considered to be an indication of an ability to treat diabetes. Therefore, our results also indicate that administration of Akkermansia inhibits the development of diabetes.” (Attachment A, para. 28, Attachment B, para. 66.) Thus, Applicants reduced the claimed invention to practice prior to the presentation of the Keystone Poster on March 6, 2012. The Patent Trial and Appeal Board (PTAB) held that the Keystone Poster was evidence of a reduction to practice of orally administering substantially purified Akkermansia to the subject wherein the substantially purified Akkermansia comprises at least 50% of a strain of Akkermansia’, in line with the subject claims. Accordingly, Applicants had an actual reduction to practice of the claimed invention prior to the presentation of the Keystone Poster on March 6, 2012, and thus the Keystone Poster is not prior art under pre-AIA 102(a) to the subject application.”
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 18-37 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for treating metabolic disorders selected from obesity, insulin-deficiency or insulin-resistance related disorders and hyperglycemia and the ability to reduce glucose levels, does not reasonably provide enablement for treating the broad genus of any and all metabolic disorders as encompassed by the breadth and scope of claim 18 and does not provide enablement for treating all of the metabolic disorders listed in claim 20. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to practice the invention commensurate in scope with these claims. The claims encompass treating a large scope of metabolic disorders by administration of A. muciniphila for which applicant is not enabled. The examples and results section enable treating the above described disorders and conditions, however, they do not enable treating the broad genus of disorders encompassed by the scope of claims 18 and 20.
One of skill in the art would not expect to be able to treat the disorders encompassed by the current claim language of the instant claims 18 and 20. Thus, with the exception of the above stated disorders and conditions, and in view of the lack of any specific guidance on treating the encompassed disorders, one skilled in the art would expect a trial and error process to determine which disorders encompassed by the claims would be treatable by simply administering A. muciniphila, and would further have to determine through undue experimentation, without guidance from the specification, which disorders are treatable.
The examples are drawn to administering A. muciniphila to mice fed control and high-fat diets and applicants find that “A. muciniphila was 3300-fold lower in leptin-deficient obese mice versus their lean littermates (Fig. la). Consistently, we found a 100-fold decrease in high-fat (HF)-fed mice (Fig. lc). In both models, prebiotics completely restore A. muciniphila count (Fig. lb,c). In HF-fed mice, prebiotics abolished metabolic endotoxemia (Fig. Id), normalized adipose tissue CD 11c subpopulation of macrophages (Fig. le) and lowered fat mass (Fig. lg and Fig.3b). Akkermansia muciniphila changes gut microbiota composition, counteracts diet-induced gut barrier dysfunction, changes intestinal level of endocannabinoids and improves metabolic disorders in diet-induced obese mice. Akkermansia muciniphila treatment reduces fat mass without affecting food intake. Akkermansia muciniphila treatment normalizes fasted glycemia and reduces fasted hepatic G6pc mRNA expression and regulates the crosstalk between the host and the gut microbiota, but also provide a rationale for considering the development of a treatment using this human mucus-colonizer for the prevention or the treatment of obesity and associated metabolic disorders.
The factors to be considered in determining whether undue experimentation is required are summarized In re Wands 858 F.2d 731, 8 USPQ2nd 1400 (Fed. Cir, 1988). The court in Wands states: "Enablement is not precluded by the necessity for some experimentation such as routine screening. However, experimentation needed to practice the invention must not be undue experimentation. The key word is 'undue,' not 'experimentation.' " (Wands, 8 USPQ2d 1404). Clearly, enablement of a claimed invention cannot be predicated on the basis of quantity of experimentation required to make or use the invention. "Whether undue experimentation is needed is not a single, simple factual determination, but rather is a conclusion reached by weighing many factual considerations." (Wands, 8 USPQ2d 1404). The factors to be considered in determining whether undue experimentation is required include: (1) the quantity of experimentation necessary, (2) the amount or direction or guidance presented, (3) the presence or absence of working examples, (4) the nature of the invention, (5) the state of the prior art, (6) the relative skill of those in the art, (7) the predictability or unpredictability of the art, and (8) the breadth of the claims.
The breadth of the current invention encompasses a method that is not supported by the present specification, nor is there evidence in the art enabling for the entire scope.
The present specification does not exemplify treating the scope of metabolic disorders encompassed by claims 18 and 20 (and 21-37), or an effective amount for treating the disorders as claimed. Therefore, based the absence of teachings or working examples provided in the present specification, the current specification is not enabled for the methods as claimed.
Applying the above test to the facts of record, it is determined that 1) no declaration under 37 C.F.R. 1.132 or other relevant evidence has been made of record establishing the amount of experimentation necessary, 2) insufficient direction or guidance is presented in the specification with respect to an effective amount for providing increases as instantly claimed, 3) the relative skill of those in the art is commonly recognized as quite high (post-doctoral level) and 7) predictability or unpredictability in the art in using the claimed microbe to treat heart disease, stroke, neurodegenerative disorder, immune disorders, sleep apnea, for example, as claimed in claim 20; and breadth of the claims. In re Wands, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988).
While the level of skill in the art is high, lack of guidance, broad scope of the claims and poorly developed state of the art would require that undue and excessive experimentation would have to be conducted by the skilled artisan in order to practice the claimed invention.
Given the above analysis of the factors which the courts have determined are critical in determining whether a claimed invention is enabled, it must be considered that undue and excessive experimentation would have to be conducted by the skilled artisan in order to practice the claimed invention.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/process/file/efs/guidance/eTD-info-I.jsp.
Claim 18-37 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 44-56 of copending Application No. 14443829 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the claimed inventions are drawn to a method of treating metabolic disorders comprising orally administering a therapeutically effective amounts of a composition containing Akkermansia. Examined claims 18-30 differ from claims 44-56 of US’829 in that the instant claims are drawn to administering a composition comprising a therapeutically effective amount of bacteria “consisting essentially of Akkermansia”, while the reference claims are drawn to administering a composition “comprising” a therapeutically effective amount of bacteria comprising Akkermansia and the reference claims include at least 50% of a strain of Akkermansia, while instant examined claims 31-37 are drawn to comprising at least about 60-99% or more of a strain of Akkermansia. Thus, the reference claims overlap and the examined claimed would be obvious over the reference claims.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 18-37 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-14 of U.S. Patent No. 10736924. Although the claims at issue are not identical, they are not patentably distinct from each other because the claimed inventions are drawn to a method of treating metabolic disorders comprising orally administering a therapeutically effective amounts of a composition comprising Akkermansia, wherein the metabolic disorders are the same. The reference claims are drawn to treating metabolic disorders comprising administering a composition comprising Akkermansia muciniphila which has been pasteurized, however the reference claims anticipate the generic examined claims, as the species of A. muciniphila including a pasteurized strain of the reference patent would anticipate the genus of Akkermansia in the examined application claims.
Claims 18-37 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 8, 9, 10, 11, 13, 17, 21, 23 of copending Application No. 16916399 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the claimed inventions are drawn to a method of treating metabolic disorders or a disorder associated with or resulting in a metabolic disorder comprising orally administering a composition comprising Akkermansia, wherein the metabolic disorder is obesity or the subject is obese (claim 23 of US’399). The reference claims are drawn to treating metabolic disorders comprising administering a composition comprising Akkermansia muciniphila which has been pasteurized, however the reference claims anticipate the generic examined claims, as the species of A. muciniphila including a pasteurized strain of the reference patent would anticipate the genus of Akkermansia in the examined application claims.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claim 18, 19, 27 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 23 of copending Application No. 18838757 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the claimed inventions are drawn to a method of treating metabolic disorders, specifically obesity and obesity-related disorders comprising administering a composition comprising Akkermansia. Thus, the reference claims overlap and the examined claimed would be obvious over the reference claims.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claim 18, 19, 27 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 15 of copending Application No. 18035766(reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the claimed inventions are drawn to a method of treating metabolic disorders, specifically obesity disorders comprising administering a composition comprising Akkermansia. While the reference claim is drawn to promoting weight loss or reducing visceral fat, one who is obese would be a subject in need of promoting weight loss or reducing visceral fat. Thus, the reference claims overlap and the examined claimed would be obvious over the reference claims.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Regarding the above ODP rejections, applicants wish to hold the rejections in abeyance until a decision is made in the related Interference.
New rejection necessitated by the filing of application 19/224071
Claim 18-37 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 18-47 of copending Application No. 19224071(reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the claimed inventions are drawn to a method of treating metabolic disorders, specifically obesity disorders comprising administering a composition comprising Akkermansia. While the reference claim is drawn to promoting weight loss, increasing energy expenditure and satiety, one who is obese would be a subject in need of promoting weight loss, increasing energy expenditure and satiety. Thus, the reference claims overlap and the examined claimed would be obvious over the reference claims.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claim Rejections - 35 USC § 103
The following is a quotation of pre-AIA 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negatived by the manner in which the invention was made.
This application currently names joint inventors. In considering patentability of the claims under pre-AIA 35 U.S.C. 103(a), the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were made absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and invention dates of each claim that was not commonly owned at the time a later invention was made in order for the examiner to consider the applicability of pre-AIA 35 U.S.C. 103(c) and potential pre-AIA 35 U.S.C. 102(e), (f) or (g) prior art under pre-AIA 35 U.S.C. 103(a).
Claim 18-21, 27 is/are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over the combination of Everard, 2011 (IDS) and Derrien et al. (Frontiers in Micro., 2011, IDS).
Everard teach that obesity and metabolic disorders are closely associated with a low-grade inflammatory state and that gut microbiota plays a critical role in the development of diabetes, obesity and insulin resistance. Everard study gut microbiota changes and metabolism in obese mice. They find that when obese mice are fed prebiotics, a wide shift in gut microbiota is seen and obesity and metabolic disorders are reduced and treated. Specifically, Everard see a dramatic increase in A. muciniphila in prebiotic fed obese mice compared to control mice. They teach that A. muciniphila is associated with a healthy mucosa and inversely correlated to body weight and increasing after RYGB surgical procedures (see entire document, specifically p. 2779, 2nd col., 2780 Table 2, p.2784, 2nd col.).
Derrien teach administering A. muciniphila to germ-free mice to study the effects of mucus degradation in the host. Derrien teach colonization of mice by administering a 109 dose of A. muciniphila to germ-free mice (p. 4, Results section). Derrien teach that the colonization of the gut leads to gut immune homeostasis (non-inflammatory) and altered expression of genes responsible for membrane metabolism, antigen presentation of leukocytes, metabolic and signaling pathways, and lipid metabolism (p. 6, 1st and 2nd col.). They also teach that the mucin degrading microbe is decreased in overweight subjects as well as IBD patients and during appendicitis but is abundant in healthy subjects thus it is associated with a healthy mucosa (p. 2, last parag.-2nd col.). Derrien also teach that A. muciniphila is found in pregnant women but is decreased in those that were overweight (p. 2, 2nd col, 1st parag.).
While the above references do not teach a method of treating metabolic disorder, each of the above references demonstrate a correlation between Akkermansia muciniphila and metabolic disorders.
At the time of the claimed invention, it would have been obvious to one of ordinary skill in the art to administer a composition comprising Akkermansia to a subject with a reasonable expectation of successfully treating a metabolic disorder, specifically obesity because the prior art teaches that the specific species of A. muciniphila is abundant in the gut mucosa in healthy subjects but is inversely correlated to body weight and significantly decreased in obese subjects. Therefore, Akkermansia and species is associated with a healthy gut mucosa and inversely correlated to obesity, thus, one of ordinary skill in the art would have been motivated to administer Akkermansia with a reasonable expectation for successfully treating a metabolic disorder in a subject in need thereof in view of the prior art of record.
Response to Arguments
Applicant's arguments filed 9/19/2025 have been fully considered. The rejections have been amended in light of the PTAB decision in Interference 106,130. Regarding the 103 rejection over Everard and Derrien, it is the examiners position that while the references do not teach treating a metabolic disorder, they do teach the concept that there is an inverse relationship between Akkermansia levels and obese subjects and that its colonization of the gut leads to gut immune homeostasis (non-inflammatory) and altered expression of genes responsible for membrane metabolism, metabolic and signaling pathways, and lipid metabolism. Therefore, one would have a reasonable expectation of successfully treating a metabolic disorder, specifically obesity when administering Akkermansia to a subject in need thereof.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to TIFFANY MAUREEN GOUGH whose telephone number is (571)272-0697. The examiner can normally be reached M-Thu 8-5.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Adam Weidner can be reached at 571-272-3045. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/TIFFANY M GOUGH/Examiner, Art Unit 1651
/Adam Weidner/SPE, Art Unit 1651