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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 5/19/2026 has been entered.
Claim Amendments
Claim 47 has been amended to require that the one or more microbial organisms comprise Prevotella or Faecalibacteriujm or a component derived therefrom, which is “present in an amount of at least 108 colony forming units (CFU)”, in combination with “Bacteroides or a component derived therefrom”. Claim 67 has also been added.
Claim Objections
Claim 47 is objected to since the first component is separated from the second component with a comma even though said components are preceded by a colon in line 1. To obviate this objection, the comma in line 6 should be replaced with a semicolon.
Claim 53 is objected to because of the following informality: the meaning of “CFU” is already established in claim 47 but is unnecessarily provided again in claim 53. It is recommended that “colony forming unit” in line 2 of claim 53 be deleted.
Claim Rejections - 35 USC § 112
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.
Claim 50-54 and 67 are rejected under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor regards as the invention.
Claims 50-51 recite that the composition “consists essentially of Prevotella histicola and Faecalibacterium prausnitzii” or “comprises Prevotella histicola and Faecalibacterium prausnitzii, or a component thereof”. It cannot be determined if these limitations (i) pertain to Prevotella and Faecalibacterium being limited to the specified species (i.e., in addition to Bacteroides or a component thereof), or (ii) require that only Prevotella and Faecalibacterium are present (i.e., excludes Bacteroides or a component thereof) as the microbial organisms in the composition and in the form of the specified species. Thus, the claims are indefinite. Claims 52-54 are also considered indefinite for depending on claim 50 or 51. In the interest of compact prosecution, the first interpretation is held.
Claim 54 recites “further comprising Bacteroides fragilis, or a component thereof”, which is confusing because it is unclear if the Bacteroides in claim 47 is specified to be B. fragilis, or if B. fragilis is present in addition to another Bacteroides. For the purpose of applying prior art, the first interpretation is taken by the examiner.
Claim 67 defines the composition as “comprises Prevotella and Faecalibacterium present at a ratio of 1:1”. It is unclear if said limitation means that (i) the Prevotella and Faecalibacterium are present in said relative amounts aside from Bacteroides or a component, or (ii) only Prevotella and Faecalibacterium are present as the microbial organisms in the composition (i.e., excludes Bacteroides or a component thereof) at the specified ratio. The instant claim is examined as if it refers to the first interpretation.
Claim Rejections - 35 USC § 103
RE: Rejection of claims 47-54, 57-60, and 62-66 under 35 U.S.C. 103 as being unpatentable over Goodman et al.; claims 47-52, 54-60, and 62-66 as being unpatentable over Goodman et al. in view of Sampson et al.; claims 47-52, 54, and 57-66 as being unpatentable over Goodman et al. in view of Scheperjans et al.
Traversal is based on Goodman et al.’s teachings being broad as said prior art discloses a lengthy list of bacterial species/strains and diseases that can be treated using any of the disclosed bacteria. It is also argued that Sampson et al. and/or Scheperjans et al. do not remedy the deficiencies of Goodman et al..
All arguments have been fully considered and are deemed persuasive. Upon re-evaluation of the cited prior art, it is conceded that Goodman et al. does not provide any guidance or reason to particularly select Prevotella or Faecalibacterium in combination with Bacteroides to prepare a pharmaceutical composition for treatment of a synucleinopathy. Hence, the rejections of record have been withdrawn.
An updated prior art search was performed and a new reference was found. Accordingly, new rejections are set forth below.
New grounds of rejections
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 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.
Claims 47-48, 54-55, 58-60, and 62-66 are rejected under 35 U.S.C. 102(a)(1)/102(a)(2) as being anticipated by Schwintner et al. (Pub. No. WO 2019/097030 A1).
Schwintner et al. provides a pharmaceutical oral formulation comprising at least two bacteria derived from fecal microbiota for the treatment and/or prevention of dysbiosis and associated pathologies. The pharmaceutical oral formulation is encapsulated in a pH responsive polymer and designed to be mainly delivered in the ileum and colon (Abstract; lines 15-17, page 5).
Preferred bacteria include Faecalibacterium prausnitzii and Bacteroides fragilis (lines 1-5, page 12). The bacteria can be isolated from a feces sample through known methods such as by culturing under conditions that favor or disfavor the growth of certain species, or by first isolating certain bacterial species from a fecal sample and then culturing the isolated bacterial species (lines 19-26, page 16).
In one embodiment, the pharmaceutical oral formulation is prepared as a capsule containing a lyophilized sample of a liquid solution comprising about 1010 bacteria (lines 6-10, page 17). The capsule can be coated with the pH sensitive polymer that does not dissolve at a pH below about 7.2 and at a thickness that slightly modifies the release time of its contents (lines 13-22, page 18; lines 17-24, page 24).
Schwintner et al. reads on the claimed invention as follows:
Regarding claim 47: the disclosed pharmaceutical oral formulation comprising at least two bacteria derived from fecal microbiota is equivalent to “A composition comprising: one or more isolated microbial organisms or a component of the isolated microbial organism”.
The at least two bacteria preferably comprising Faecalibacterium prausnitzii and Bacteroides fragilis (lines 1-5, page 12) meets “wherein the one or more isolated microbial organisms comprise Prevotella or Faecalibacterium or a component derived therefrom… and Bacteroides or a component derived therefrom”.
The embodiment of the pharmaceutical oral formulation being a capsule containing about 1010 bacteria (lines 6-10, page 17) satisfies “the Prevotella or Faecalibacterium present in an amount of at least 108 colony forming units (CFU)” and the requirement that the claimed composition is “formulated as a supplement, a powder, a pill, a tablet, a capsule, a pharmaceutical composition…”.
The capsule being coated with a pH responsive polymer designed not to dissolve below about pH 7.2 such that the contents are primarily released in the ileum and colon (lines 13-22, page 18), wherein the thickness of the coating can be modified to modify release time (lines 17-22, page 24), fulfills “wherein the composition is formulated for controlled release within the lower intestine or colon”.
Regarding claim 48: the at least two bacteria derived from fecal microbiota being cultured is the same as “wherein the one or more isolated microbial organisms are cultured bacteria”.
Regarding claim 54: the at least two bacteria comprising B. fragilis corresponds to “further comprising Bacteroides fragilis, or a component thereof”. As set forth above (see rejection under 112(b)), this limitation is interpreted to mean the Bacteroides in claim 47 is specified to be B. fragilis.
Regarding claim 55: the capsule being coated with a pH responsive polymer that does not release contents at pH below about 7.2 (i.e., does not dissolve in acidic conditions; lines 11-16, page 32; lines 21-24, page 33) is akin to “wherein the composition is formulated in an acid-resistant formulation”.
Regarding claim 58: administering the disclosed oral pharmaceutical formulation to a subject to treat dysbiosis or a related pathology such as Parkinson’s disease (lines 27-28, page 25; lines 1-8, page 26; lines 23-28, page 28; line 5, page 29), which is a type of synucleinopathy, is analogous to “A method of inhibiting, reducing, delaying, preventing, or ameliorating a synucleinopathy, or one or more symptoms of a synucleinopathy, the method comprising: administering to a subject in need the composition of claim 47”.
Regarding claim 59: Parkinson’s disease is a neurodegenerative disease and therefore meets “wherein the synucleinopathy is a neurodegenerative disorder, an enteric nervous system disorder, or inflammation associated thereto”.
Regarding claim 60: the subject being treated is a mammal such as a human (line 22, page 17) suffering, or at risk from developing, dysbiosis or a related pathology (lines 1-3, page 26; lines 26-28, page 28). Given that the disease being treated includes Parkinson’s disease, the subject being administered with the disclosed composition is implied to suffer or at risk from developing Parkinson’s disease, which satisfies “wherein said subject is one that has been identified or selected as being at risk for developing or already having Parkinson's disease, such as by clinical or diagnostic evaluation”.
Regarding claim 62: since Parkinson’s disease is characterized by increased aggregation of α-synuclein, the subject necessarily has “an abnormal level of aggregation of a-synuclein (αSyn)”.
Regarding claim 63: treating gut dysbiosis and related pathologies like gastrointestinal disorders (lines 17-21, page 4; lines 1-5, page 5; lines 24-28, page 26) by delivering the disclosed oral pharmaceutical formulation to a subject’s ileum and colon results in a more balanced microbiome in the gastrointestinal tract and healthier gut, thereby fulfilling “wherein the method improves one or more gastrointestinal functions of the subject”.
Regarding claims 64-65: Schwintner et al. does not explicitly teach that using the disclosed oral pharmaceutical formulations leads to “reduces aSyn aggregated in the subject” and “reduces neuroinflammation in the subject”, respectively.
It should be noted that a chemical composition and its properties are inseparable. Thus, if the prior art teaches the chemical composition, the properties are necessarily present. With the presence of all the recited components, the disclosed pharmaceutical composition is deemed structurally the same as the composition being administered in the claimed method. MPEP § 2112 states that “[T]he discovery of a previously unappreciated property of a prior art composition, or of a scientific explanation for the prior art’s functioning, does not render the old composition patentably new to the discoverer.” Atlas Powder Co. v. Ireco Inc., 190 F.3d 1342, 1347, 51 USPQ2d 1943, 1947 (Fed. Cir. 1999). Thus the claiming of a new use, new function or unknown property which is inherently present in the prior art does not necessarily make the claim patentable. In re Best, 562 F.2d 1252, 1254, 195 USPQ 430, 433 (CCPA 1977). The disclosed pharmaceutical composition is therefore necessarily capable of reducing aSyn aggregated in the subject and decreasing neuroinflammation in the subject even though said properties are not acknowledged by Schwintner et al..
Regarding claim 66: the prior art teaches delivering the oral pharmaceutical formulation comprising bacteria in an amount that significantly increases the final relative population of said bacteria in the gut, such as the relative abundance of F. prausnitzii in the gut (lines 8-17, page 29), which is the same as “wherein the method increases levels of gut Prevotella histicola or Faecalibacterium prausnitzii”.
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.
Claims 47-55, 57-60, and 62-67 are rejected under 35 U.S.C. 103 as being unpatentable over Schwintner et al. (Pub. No. WO 2019/097030 A1) in view of Goodman et al. (Pub. No. WO 2019/051381 A1).
The teachings of Schwintner et al. are set forth above and applied herein. Schwintner et al. is found to anticipate claims 47-48, 54-55, 58-60, and 62-66.
Schwintner et al. is comparable to the claims below:
Regarding claim 49: the composition of claim 47 has the additional limitation “wherein the components of the isolated microbial organism comprise bacterial outer membrane vesicles derived from the isolated microbial organism”.
Schwintner et al. is different from the instant claim in that the disclosed oral pharmaceutical formulation does not comprises bacterial outer membrane vesicles.
Goodman et al., however, teaches that extracellular vesicles (EVs) of Prevotella bacteria and said bacteria per se are useful for treating and/or preventing a disease or disorder including inflammatory bowel diseases and neurodegenerative diseases like Parkinson’s disease (par. [2], [180], [186], [202]). Thus, Goodman et al. provides pharmaceutical compositions comprising Prevotella EVs and/or Prevotella bacteria like P. histicola (par. [86]), wherein said pharmaceutical compositions can be prepared in the form of capsules (par. [126]).
Given that Schwintner et al. teaches that the oral pharmaceutical composition can include probiotics (lines 15-17, page 31) and Goodman et al. teaches that Prevotella EVs and/or Prevotella bacteria can be utilized to treat a disease or disorder including inflammatory bowel diseases and neurodegenerative diseases like Parkinson’s disease, a person with ordinary skill in the art before the effective filing date of the claimed invention would have incorporated Prevotella EVs and/or Prevotella bacteria like P. histicola to Schwintner et al.’s oral pharmaceutical formulation with reasonable expectation that administering it to a subject suffering from, or at risk of developing, dysbiosis or related pathology such as Parkinson’s disease would be treated. The rationale to support obviousness is that all claimed elements were known in the prior art and their combination would yielded nothing more than predictable results. See MPEP § 2143 and KSR, 550 U.S. 398, 82 USPQ2d at 1395.
Hence, claim 49 is obvious over Schwintner et al. in view of Goodman et al..
Regarding claims 50-51: the modified oral pharmaceutical composition comprising at least two bacterial species including F. prausnitzii and Prevotella bacteria like P. histicola meets “the composition consists essentially of Prevotella histicola and Faecalibacterium prausnitzii” or “the composition comprises Prevotella histicola and Faecalibacterium prausnitzii, or a component thereof”.
Regarding claim 52: the F. prausnitzii and Prevotella bacteria like P. histicola being combined in the modified oral pharmaceutical composition corresponds to “wherein the P. histicola and the F. prausnitzii are in a single composition”.
Regarding claims 53 and 67: the P. histicola and F. prausnitzii in the composition of claim 50 are each further required to be “present in an amount of at least 108 colony forming units (CFU)” (claim 53), while the composition of claim 47 is further stipulated to comprise “Prevotella and Faecalibacterium present at a ratio of 1:1” (claim 67).
Schwintner et al. only teaches that about 1010 of bacteria like F. prausnitzii are present in a capsule (lines 5-18, page 17). Although said prior art is silent about P. histicola and does not particularly teach the relative amounts of the different species of bacteria, Goodman et al. states that the dose must be sufficient to delay the onset, slow/stop the progression, or prevent the disease being treated, and that it can be determined by conventional range-finding techniques by those of ordinary skill in the art. Goodman et al. also teaches that the dosage depends on a variety of factors including the age, species, condition, and body weight of the subject, as well as the route, timing, and frequency of administration (par. [172]-[174]). Thus, the claimed amount of F. prausnitzii and P. histicola can be characterized as routine optimization and experimentation that can be determined by a person with ordinary skill in the art. See MPEP § 2144.05 (II). Furthermore, differences in concentration does not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration 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).
Regarding claim 57: the composition of claim 47 is further specified to comprise “an anti-inflammatory agent”.
Schwintner et al. differs from the instant claim in that the oral pharmaceutical composition does not contain an anti-inflammatory agent.
Nonetheless, Goodman et al. teaches an embodiment wherein the subject is also administered with an anti-inflammatory agent (par. [8], [128], [167], [334], [339]). Since Schwintner et al. and Goodman et al. are directed to using bacteria-containing compositions to treat dysbiosis and/or an associated pathology like inflammatory bowel disease and Parkinson’s disease (which is characterized by neuroinflammation and gut inflammation), it would have been obvious to further alter the modified oral pharmaceutical formulation by adding an anti-inflammatory agent. Such modification is expected to provide the benefit of alleviating inflammation in the subject. The obviousness of the instant claim is based on 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. See MPEP § 2143.01 and KSR International Co. v. Teleflex Inc., 550 U.S. 398, 82 USPQ2d 1385, 1395-97 (2007).
Claims 47-55 and 57-67 are rejected under 35 U.S.C. 103 as being unpatentable over Schwintner et al. (Pub. No. WO 2019/097030 A1) in view of Goodman et al. (Pub. No. WO 2019/051381 A1) and Scheperjans et al. (Pub. No. US 2017/0191998 A1).
Schwintner et al. and Goodman et al.’s teachings are discussed previously and applied herein. Schwintner et al. is found to anticipate claims 47-48, 54-55, 58-60, and 62-66, whereas the combined teachings of Schwintner et al. and Goodman et al. render claims 47-55, 57-60, and 62-67 obvious.
Schwintner et al. is similar to the following claim:
Regarding claim 61: the subject is further required to be “selected as in need of the composition if a presence of Prevotella histicola or Faecalibacterium prausnitzii in an intestinal sample is lower than a predetermined level or control”.
Neither Schwintner et al. nor Goodman et al. teaches that the subject being treated has a lower level of either bacterial species compared to a predetermined level or control.
Despite this, Scheperjans et al. teaches methods for early detection of Parkinson’s disease and treatment or prophylaxis of said disease (Abstract; par. [0006]). The methods comprise obtaining a sample from a subject, determining the relative abundances of at least one Prevotellaceae taxa in the sample, and determining probability of the subject developing or having Parkinson’s disease based on the measured relative abundances (par. [0007]). This is based on the finding that a high relative abundance of Prevotellaceae indicates a low probability of the subject developing or having the disease. Preferably, the microbial taxa is Prevotella (par. [0044]-[0045]). A low relative abundance of Prevotella is one indicator that the subject has a high probability of developing or having Parkinson’s disease (par. [0049]).
Since Schwintner et al. teaches that the amount bacteria should be enough to significantly increase the relative abundance of the bacteria being delivered and since the modified oral pharmaceutical formulation comprises Prevotella histicola, one with ordinary skill in the art would have been motivated to further modify Schwintner et al. and Goodman et al. by measuring the relative abundance of Prevotella such as P. histicola in the subject because it would allow early detection of Parkinson’s disease or identification of the subject as being at risk for having said disease. This is advantageous since the subject can receive early treatment. Obviousness is established by combining or modifying the teachings of the prior art to produce the claimed invention where there is some teaching, suggestion, or motivation to do so. Id.
Claim 61 is thus obvious over Schwintner et al. in view of Goodman et al. and Scheperjans et al..
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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