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 .
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 5/13/2026 has been entered.
Claim Amendments
Applicant has amended claim 43 to specify that the Parabacteroides goldsteinii bacteria have been inactivated only “via exposure to heat” in limitation (i) and to omit limitation (ii). In addition, claims 44 and 57-58 have been canceled.
Claims 43 and 45-45-56 remain pending and have been examined on the merits.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 2/03/2026 is in compliance with the provisions of 37 C.F.R. 1.97. Both cited references have been fully considered.
Drawings
RE: Objection to the drawings
The replacement drawings are sufficient to overcome all minor informalities in Figures 9-10, 11A-11B, and 12A-12B. Thus, the objection to the drawings has been withdrawn.
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.
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.
RE: Rejection of claims 43-52 and 57-58 under 35 U.S.C. 103 as being unpatentable over Goodman et al. in view of Grant et al., Wu et al., and Hussan et al., as evidenced by Sakamoto et al.
Applicant argues that the pending claims “require a single species” of heat-inactivated bacteria that are formulated for delivery to the gastrointestinal system (last par., page 5 or Applicant Arguments/Remarks). Referring to Goodman et al.’s list of over 1875 bacteria, applicant also contends that said prior art does not provide a finite number of predictable solutions as the list includes toxic bacteria, nor a scientific reasoning for using them to treat any of the named diseases. It is further asserted that the other cited references do not cure the deficiencies of Goodman et al.. Grant et al.’s teaching of Parabacteroides strains being killed, attenuated, or inactivated allegedly only pertains to vaccine compositions and are not taught be administered to a subject’s gastrointestinal system. Grant et al. also focuses on P. distasonis and not P. goldsteinii. Furthermore, Wu et al. teaches away from using heat-inactivated P. goldsteinii.
All arguments have been fully considered and are found partly persuasive.
First, the claims use the transitional phrase “comprising”, which is an open language. Thus contrary to applicant’s first argument, the claimed composition can contain other components including other bacterial species.
Second, Goodman et al. does list numerous bacterial species and diseases. But according to MPEP § 2131.02(II), a prior art that names the claimed species anticipates the claim regardless of the number of other named species. See Ex parte A, 17 USPQ2d 1716 (Bd. Pat. App. & Inter. 1990) (The Board held that the comprehensiveness of the listing did not negate the fact that the compound claimed was specifically taught). It should also be noted that obviousness of the claimed invention was based not only on Goodman et al. but also on the teachings of Grant et al. and Wu et al., which provide a reason or motivation to select P. goldsteinii strain as the bacteria in Goodman et al.’s pharmaceutical compositions.
Although Grant et al. only explicitly teaches formulating killed, attenuated, or inactivated bacterial strains as vaccine compositions, it does not necessarily mean they are not suitable for delivery to the gastrointestinal system. Oral vaccines are known in the art and such formulations are routinely prepared with enteric coatings or embedded within liposomes/microparticles to ensure protection from acid or enzyme degradation in the gastrointestinal tract. Moreover, it does not invalidate the overall teaching that Parabacteroides strains are useful for treating cancer, inflammatory diseases, and autoimmune diseases. And as discussed in the last office action, preferred embodiments do not constitute a teaching away from nonpreferred embodiments.
On the other hand, it is conceded that Wu et al. teaches away from choosing heat-inactivated P. goldsteinii to be the bacteria in the disclosed pharmaceutical composition. Wu et al. concludes that live P. goldsteinii bacteria are required to be effective (albeit this refers only to said bacteria’s effectiveness to reduce body weight and visceral fat accumulation).
Since another prior art is now considered to read more closely on the claimed invention, the rejections of record have been withdrawn. New grounds of rejection are set forth below.
New grounds of rejection
Claims 43 and 45-47 are rejected under 35 U.S.C. 103 as being unpatentable over Goodman et al. II (Pub. No. WO 2018/112365; cited in a previously filed IDS) in view of Pique et al. (International Journal of Molecular Sciences 2019, Vol. 20, pages 1-30; cited in newly submitted IDS) and Goodman et al. (Pub. No. WO 2019/051380A1).
Goodman et al. II discloses a bacterial composition comprising Parabacteroides goldsteinii for treatment of colorectal cancer and/or melanoma (Abstract; par. [002], [035]), wherein said bacterial species can be killed, live, and/or attenuated (par. [003], [040]; claims 105-106). The bacterial composition can be administered orally (par. [0004], [015]). In an embodiment, the P. goldsteinii is provided as a pharmaceutical composition in combination with a pharmaceutically acceptable carrier (par. [007]).
Goodman et al. II is comparable to the following claims: Regarding claim 43: the embodiment of the bacterial composition being a pharmaceutical composition (par. [007]) comprising killed or attenuated P. goldsteinii (par. [003], [040]; claims 105-106), wherein the dosage of the bacteria depends on various factors such as the subject’s size and kind of disease (par. [067]), is similar to “A pharmaceutical or probiotic composition comprising a therapeutically effective amount of inactivated Parabacteroides goldsteinii”.
The bacterial composition being administered orally to a subject results in the delivery of the composition to the subject’s gastrointestinal system, thus meeting the limitation “wherein the composition is formulated for delivery to the gastrointestinal system”.
What differentiates Goodman et al. II from the claimed composition is that it does not specifically teach that the P. goldsteinii bacteria “have been inactivated via exposure to heat”.
Inactivation or heat-killing, however, is a known technique in the art as shown by Pique et al. and Goodman et al.. Pique et al. teaches that there are different methods of inactivating bacteria, one of which is heat treatment (section 4, page 7). Heat treatment involves subjecting bacteria to temperatures of between 70 and 100°C, which can be combined with incubation at lower temperatures. Heat-killed bacteria or their fractions/components have probiotic effects and offer various advantages compared to live bacteria (Abstract, page 1; Table 1, page 3). This teaching is supported by Goodman et al., which teaches that bacteria like P. goldsteinii can be killed or attenuated using heat prior to administration such as by oral means (par. [342], [352], [363], [392], [398], [412], and [419]). It would have therefore been obvious for one with ordinary skill in the art to treat P. goldsteinii with heat as taught by Pique et al. and Goodman et al. and formulate the resulting heat-killed bacteria as a pharmaceutical composition for therapeutic use. Applying a known technique to a known product ready for improvement yields predictable results. See MPEP § 2143 and KSR International Co. v. Teleflex Inc., 550 U.S. 398, 82 USPQ2d 1385, 1395-97 (2007).
Thus, claim 43 is obvious over Goodman et al. II in view of Pique et al. and Goodman et al..
Regarding claims 45-46: the pharmaceutical or probiotic composition of claim 43 is required to comprise “Lactobacillus gasseri or Lactobacillus reuteri” or further comprise “extracellular vesicles from Lactobacillus gasseri or extracellular vesicles from Lactobacillus reuteri”. Goodman et al. II teaches that the disclosed bacterial composition contains at least 50% P. goldsteinii, suggesting that other bacterial species can be present.
Although Goodman et al. II does not specify what other bacteria can be included, it is known in the art that lactic acid bacteria confer several health benefits as substantiated by Pique et al.. Pique et al. states that strains of Lactobacillus serve as probiotics that balance gut microbiota, protect against pathogens, and maintain intestinal barrier integrity (second and third par. in page 2). Heat-killed lactic acid bacteria are found to have immunomodulating effects. For example, heat-killed L. reuteri induces IL-12 which activates natural kills cells and increases IFN-γ production, thereby boosting the immune system. Cell-free supernatants of said bacteria also exhibit anti-inflammatory activity (Table 2, page 10). And since Goodman et al. teaches combining different species of whole bacteria and/or bacterial extracellular vesicles (EVs) in a pharmaceutical composition for treatment of diseases like cancer (par. [2]) including P. goldsteinii, L. gasseri (Table 1, page 60), and L. reuteri (Table 1, page 61), a person with ordinary skill in the art would have added lactic acid bacteria like L. reuteri to the P. goldsteinii-containing pharmaceutical composition with reasonable expectation that it would provide the benefit of improving the immune system. The rationale to support obviousness is that all claimed elements were known in the prior art and their combination would have yielded nothing more than predictable results. See MPEP § 2143 and KSR, 550 U.S. 398, 82 USPQ2d at 1395.
Regarding claim 47: the pharmaceutical composition being formulated for oral administration meets “wherein the pharmaceutical or probiotic composition is formulated for oral, colonic, enema, orogastric, or nasogastric administration”.
Claims 43 and 45-52 are rejected under 35 U.S.C. 103 as being unpatentable over Goodman et al. II (Pub. No. WO 2018/112365; cited in a previously filed IDS) in view of Pique et al. (International Journal of Molecular Sciences 2019, Vol. 20, pages 1-30; cited in newly submitted IDS), Goodman et al. (Pub. No. WO 2019/051380A1), and Hussan et al. (IOSR Journal of Pharmacy 2012, Vol. 2, pages 5-11).
The teachings of Goodman et al. II, Pique et al., and Goodman et al. are set forth above and applied herein. These references render claims 43 and 45-47 obvious.
The modified pharmaceutical composition is analogous to the claims below:
Regarding claim 48: the pharmaceutical or probiotic composition of claim 43 is further stipulated to be “resistant to degradation in the stomach but releases bacteria in the small intestine and/or large intestine of the subject”.
Goodman et al. II does not teach the limitation of the instant claim.
Nevertheless, formulating compositions containing biological materials like bacteria with an enteric coating is known in the art. Hussan et al., for example, teaches that an enteric coating is a barrier that control the location of oral medication in the digestive system where it is absorbed. An enteric coating remains insoluble at low pH and therefore prevents release of the contents before the small intestine is reached, but becomes soluble as the pH increases when exposed to the intestinal fluid. Typical materials used as enteric coatings include CAP, CAT, PVAP, HPMCP, fatty acids, waxes, shellac, plastics, and plant fibers. Hussan et al. teaches that formulating a tablet or capsule with an enteric coating offers various advantages such as protection of active ingredients from the acidic environment of the stomach, prevention of gastric distress or nausea due to irritation, optimal absorption in the small intestine, provision of a delayed-release component for repeat action, and minimization of first pass metabolism (Abstract; section II, page 6).
A person with ordinary skill in the art before the effective filing date of the claimed invention would have been motivated by Hussan et al.’s teachings to modify the pharmaceutical composition of Goodman et al. II by preparing it with an enteric coating using a material like CAP, CAT, PVAP, HPMCP, fatty acids, waxes, shellac, plastics, or plant fibers because of the various benefits it provides. The presence of an enteric coating would prevent the bacteria from being degraded in the subject’s stomach and would ensure they are delivered to the small intestine. Some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention. Id.
Hence, claim 48 is obvious over Goodman et al. II in view of Pique et al., Goodman et al., and Hussan et al..
Regarding claim 49: the enteric coating in the modified pharmaceutical composition satisfies “wherein the pharmaceutical or probiotic composition comprises an enteric coating, chitosan-alginate beads, or a hydrogel”.
Regarding claim 50: the enteric coating being made with CAP, CAT, PVAP, HPMCP, fatty acids, waxes, shellac, plastics, or plant fibers is the same as “the enteric coating is a fatty acid, a wax, a shellac, a plastic such as a phthalate, CAP, CAT, PVAP, HPMCP, or a plant fiber”.
Regarding claim 51: Goodman et al. II teaches embodiments wherein the disclosed bacterial composition is prepared as a food product in the form of liquids, pastes, and jellies (par. [063]), which are product forms that do not comprise an enteric coating and therefore fulfills “wherein the pharmaceutical or probiotic composition does not comprise an enteric coating”.
Regarding claim 52: formulating the bacterial composition as tablets or capsules (par. [063]) corresponds to “wherein the pharmaceutical or probiotic composition is a tablet or capsule”.
Claims 43, 45-47, and 53-56 are rejected under 35 U.S.C. 103 as being unpatentable over Goodman et al. II (Pub. No. WO 2018/112365; cited in a previously filed IDS) in view of Pique et al. (International Journal of Molecular Sciences 2019, Vol. 20, pages 1-30; cited in newly submitted IDS), Goodman et al. (Pub. No. WO 2019/051380A1), Ramos-Molina et al. (Frontiers in Nutrition 2019, Vol. 6, article 24, pages 1-15), and Sadasivan et al. (European Journal of Pharmacology 2014, Vol. 729, pages 94-99).
Goodman et al. II, Pique et al., and Goodman et al.’s teachings are described previously and applied herein.
The modified pharmaceutical composition is comparable to the instant claims:
Regarding claim 53: the pharmaceutical or probiotic composition of claim 43 has the additional limitation “further comprises spermine or spermidine”.
Goodman et al. II differs from the instant claim in that the disclosed composition does not contain spermine or spermidine.
Despite this, Ramos-Molina et al. teaches that spermidine and spermine are widely distributed polyamines that are essential for cellular functions. For instance, inactivation of genes controlling the biosynthesis of spermidine or its precursor putrescine is embryo-lethal in mice given that they interact with nucleic acids and can therefore affect many processes in which DNA, RNA, or proteins act as substrates (Abstract, page 1; last par., left col. and first par., right col., page 2).
Moreover, dysregulation of polyamine metabolism has been shown to affect regulation of glucose, lipid, and energy homeostasis. Studies suggest that increased levels of polyamines in white adipose tissue, liver, or skeletal muscle stimulate energy expenditure and confer resistance to diet-induced obesity and non-alcoholic fatty liver disease. Obesity animal models also show altered levels of polyamines in adipose tissue, liver, pancreatic islets, and urine (last par., right col., page 7). In diet-induced obesity mouse models, a high-dose daily administration of spermidine or spermine has been shown to be an effective strategy for weight loss and improvement of the glycemic status. Spermidine supplementation, for example, resulted in a significant decrease in body weight, increased glucose tolerance and insulin sensitivity and ameliorated hepatic steatosis in high-fat diet-induced obese mice. Administration of spermidine is also shown to prevent lipid accumulation and necrotic core formation in vascular smooth muscle cells through the induction of cholesterol efflux in an experimental model of atherosclerosis. Similarly, treatment with exogenous spermine led to decreased body weight and fasting glucose, as well as improved glucose tolerance in diet-induced obese mice. Spermine is also found to enhance glucose transport and the conversion of glucose into triacylglycerols in cultured rat adipocytes, and increase the ability of insulin to bind to its own receptor (first two par., left col., page 8).
Furthermore, Sadasivan et al. demonstrates that administering 10 mg of spermine per kg body weight to high fat diet-induced obese mice twice daily for 4 weeks decreased body weight by 24% and fasting glucose level by 18% (Abstract, page 94; section 2.1, page 95). Exogenous administration of spermine is therefore useful for controlling glucose and lipid metabolism in obese subjects (first par., left col., page 95).
One with ordinary skill in the art before the effective filing date of the claimed invention would have been motivated to add spermine and/or spermidine to the modified pharmaceutical composition comprising P. goldsteneii. Such addition is expected to help treat a metabolic disease or disorder based on the teachings of Ramos-Molina et al. and Sadasivan et al.. Some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art references to arrive at the claimed invention. Id.
Claim 53 is therefore obvious over Goodman et al. II in view of Pique et al., Goodman et al., Ramos-Molina et al., and Sadasivan et al..
Regarding claims 54-56: the pharmaceutical or probiotic composition of claim 53 is further limited to comprise “spermine”, “spermidine”, or “both spermine and spermidine”, respectively, which are considered obvious as explained above.
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 filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual 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/apply/applying-online/eterminal-disclaimer.
RE: Nonstatutory double patenting rejection
Applicant traverses the rejection based on co-pending Application 18/619514 being a later-filed, unrelated application.
The claims of the instant application are not yet in condition for allowance. Accordingly, the double patenting rejection over said co-pending application is maintained for the remaining pending claims.
Maintained double patenting rejection
Claims 43 and 45-56 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-15, 17-29, 32-40, 45-49, 53, 55, and 59 of co-pending Application No. 18/619514.
Co-pending application 18/619514 is drawn to a method of treating a disease in a mammalian subject comprising administering to the mammalian subject a therapeutically relevant amount of a composition, as well as a pharmaceutical or probiotic composition. Like the instant application’s pharmaceutical or probiotic composition, the co-pending application’s pharmaceutical or probiotic composition comprises: (i) P. goldsteinii, the growth medium of P. goldsteinii, or vesicles from P. goldsteinii, and (ii) a biphosphate; wherein the composition is formulated for delivery to the gastrointestinal system.
The P. goldsteinii can be heat-inactivated and additionally combined with L. gasseri, L. reuteri, Akkermansia muciniphila, or extracellular vesicles from P. goldsteinii. In one embodiment, the composition further comprises spermine and/or spermidine.
The pharmaceutical or probiotic composition can be resistant to degradation in the stomach but releases bacteria in the small intestine and/or large intestine of the subject. It can be provided in the form of a tablet or capsule. In some embodiments, it comprises an enteric coating, chitosan-alginate beads, or a hydrogel, wherein the enteric coating can be a fatty acid, a wax, a shellac, a plastic such as a phthalate, CAP, CAT, PVAP, HPMCP, or a plant fiber. In another embodiment, the pharmaceutical or probiotic composition does not comprise an enteric coating.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MICHELLE F PAGUIO FRISING whose telephone number is (571)272-6224. The examiner can normally be reached Monday-Friday, 8:00 a.m. - 4:00 p.m..
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/Michelle F. Paguio Frising/Primary Examiner, Art Unit 1651
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