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 .
Claim Status
The amended claim set filed 15 Mar 2023 is acknowledged. Claims 17-35 are currently pending. Of those, all claims are new. Claims 1-16 are cancelled. Claims 17-35 will be examined on the merits herein.
For clarity of the record, references to the specification will refer to paragraph numbers from the Pre-Grant Publication (US-20230355688-A1; PTO-892) to avoid confusion if amendments to the specification change the page and line numbers of text being cited.
Priority
The priority claim to EP20306033.0 (filed 15 Sep 2020) is acknowledged. Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55. The instant case is a 371 of PCT/EP2021/075363 (filed 15 Sep 2021). The effective filing date used for searching the art is 15 Sep 2020.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 15 Mar 2023 was filed in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement has been considered by the examiner. A signed copy of the statement is attached with this action.
Claim Rejections - 35 USC § 112(d)
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 24 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Regarding claim 24, the claim depends from claim 17 (“…administering to said individual a bacterial strain of the species Parabacteroides distasonis…”), and reads “wherein the said bacterial strain is in a live; semi-active; inactivated, and/or dead form.” First, the specification states “ the term “inactivated” also designates the extracts and lysates of bacterial strains” [0101]. Extracts and lysates do not fall within the generally accepted definition of the term “bacterial strain”, which is understood to refer to a whole cell, so the claimed “inactivated form” is broader than the parent claim and fails to include the “bacterial strain” limitation from claim 17.
Second, this list of options appears to encompass all possible states for the bacterial strain, so including all possible states in a single claim means claim 24 does not further limit claim 17. One or more of the claimed options should be deleted or moved to a separate dependent claim so that claim 24 limits the bacteria states (or applicant may or present a sufficient showing that the dependent claim(s) complies with the statutory requirements).
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 17-31 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.
Regarding claim 17, the claim reads “method for the … prevention of a gastrointestinal disease, or of a disorder associated with a gastrointestinal disease in an individual…”. The term “prevent” is defined in the specification at [0069]: “the term “ prevent” denotes the reduction to a lesser degree of the risk or of the probability of occurrence of a given phenomenon”. However, the risk or of the probability of occurrence of a given phenomenon cannot be determined on the level of a single individual. If a disease has a baseline risk of 0.6, and the method successfully lowers the risk to 0.3, then subjects who have successfully been administered a preventative method will include both subjects who get the disease and subjects who do not. But, subjects who have unsuccessfully been administered the same composition but not had prevention will also include both subjects who get the disease and subjects who do not. There is no way for one of ordinary skill in the art to identify individuals where the method successfully accomplished the goal of prevention in comparison to individuals with unsuccessful prevention. The primary purpose of this requirement of definiteness of claim language is to ensure that the scope of the claims is clear so the public is informed of the boundaries of what constitutes infringement of the patent. Therefore, this claimed limitation fails to “particularly point out and distinctly define the metes and bounds of the subject matter to be protected by the patent grant” as required by MPEP 2171. Dependent claims 18-31 are also rejected because they depend from claim 17 and do not obviate this grounds of rejection.
Regarding claims 17 and 27, the term “associated with” in claims 17 and 27 is a relative term which renders the claim indefinite. The term “associated” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. The specification gives examples of diseases “associated with” an inflammatory gastrointestinal disease at [0137], but explicitly states that it is not a complete list (the diseases “include” the listed ones). Therefore, one of ordinary skill in the art would not be able to determine what types of associations or how strong of an association is required by the claim. Dependent claims 18-30 are also rejected because they depend from claims 17 and/or 27 and do not obviate this grounds of rejection. Claim 31 is not included in this rejection because it defines a specific disorder. In the interest of compact prosecution, in this action, the diseases specifically listed in the specification will be examined.
Regarding claim 27, the claim recites “inflammatory gastrointestinal diseases”, but the specification does not define this term or provide any standard for determining which diseases fall into this claimed group. The best description in the specification is at [0137], which gives the examples of Crohn’s disease and IBD as types of inflammatory gastrointestinal diseases. However, this is not a limiting definition of disease types because dependent claim 29 also be ulcerative colitis or pouchitis. Therefore, the claim is indefinite because it is unclear what diseases’ treatments are claimed. In the interest of compact prosecution, in this action, the diseases specifically listed in the specification and claims will be examined.
Claim Rejections - 35 USC § 112(a)
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 17-35 are rejected under 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph, as failing to comply with the enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
It is apparent that the bacterial strain deposited with the CNCM under accession number CNCM I-5576 and the bacterial strain deposited with the CNCM under accession number CNCM I-5578 are both required to practice the claimed inventions. As such the biological material must be known and readily available or obtainable by a repeatable method set forth in the specification, or otherwise known and readily available to the public. If it is not so obtainable or available, the requirements of 35 USC 112(a) or pre-AIA 35 U.S.C. 112, first paragraph, may be satisfied by a deposit of the P. distasonis strains.
The process disclosed in the specification to obtain these strains does not appear to be repeatable, it is not clear that the invention will work with commonly available material and it is not apparent if the biological materials considered necessary to make and use the invention is both known and readily available to the public. It is noted that all three of CNCM I-5576, CNCM I-5577, and CNCM I-5578 were all derived from the same source [Table 1, 0167], but each strain has unique properties as shown in the examples. Therefore, a deposit at a recognized depository may be made to obviate this rejection.
It is noted that Applicants have deposited biological material but there is no indication in the specification as to public availability.
If the deposit is made under the terms of the Budapest Treaty, then a statement, affidavit or declaration by Applicants, or by an attorney of record over his or her signature and registration number, or by someone in a position to corroborate the facts of the deposit, that the instant invention will be irrevocably and without restriction released to the public upon the issuance of a patent, would satisfy the deposit requirement made herein.
If the deposit is a non-Budapest Treaty deposit, then in order to certify that the deposit meets the requirements set forth in 37 CFR 1.801-1.809 and MPEP 2402-2411.05, a statement, affidavit or declaration by Applicant or by an attorney of record over his or her signature and registration number, or by someone in a position to corroborate the facts of the deposit would satisfy the requirements herein by stating and providing that:
(a) During the pendency of the application, access to the invention will be afforded to the Commissioner upon request;
(b) All restrictions upon availability to the public will be irrevocably removed upon granting of the patent;
(c) The deposit will be maintained in a public depository for a period of 30 years, or 5 years after the last request or for the enforceable life of the patent, whichever is longer; and
(d) Provide evidence of the test of the viability of the biological material at the time of deposit (see 37 CFR 1.807).
Claims 17-31 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 achieving an anti-inflammatory effect, improving the gastrointestinal epithelial barrier, and treating colitis using either Parabacteroides distasonis CNCM I-5576 or CNCM I-5588, and of treating obesity with P. distasonis CNCM I-5588, does not reasonably provide enablement for the treatment and/or prevention of a gastrointestinal disease, or of a disorder associated with a gastrointestinal disease, or the specific diseases of claims 27-31 with at least one bacterial strain selected from P. distasonis CNCM I-5576 and CNCM I-5578. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
The factors to be considered in determining whether a disclosure would require undue experimentation include: (A) The breadth of the claims; (B) The nature of the invention; (C) The state of the prior art; (D) The level of one of ordinary skill; (E) The level of predictability in the art; (F) The amount of direction provided by the inventor; (G) The existence of working examples; and (H) The quantity of experimentation needed to make or use the invention based on the content of the disclosure. In re Wands, 8 USPQ2d, 1400 (CAFC 1988) and MPEP 2164.01. Although all factors were considered, the Wands factors that were most relevant for this decision are discussed in detail below.
The breadth of the claims: The claims require administering compositions comprising at least one bacterial strain selected from P. distasonis CNCM I-5576 and CNCM I-5578, or both strains in the case of dependent claim 20, in various forms including live, semi-active, inactive, and dead, where the bacteria is in any dose and combined with any other ingredients.
This method claims that the administration achieves the function of being “for the treatment and/or prevention of a gastrointestinal disease, or of a disorder associated with a gastrointestinal disease”. Dependent claim 27 limits the method to being “for the treatment and/or prevention of: inflammatory gastrointestinal diseases, disorders associated with an inflammatory gastrointestinal disease, and/or a leaky gastrointestinal barrier”; claims 28-30 limit the inflammatory gastrointestinal disease to being inflammatory bowel disease, being specifically Crohn’s disease, ulcerative colitis, or pouchitis, or being a colonic inflammatory bowel disease, respectively; and claim 31 limits the disorder associated with an inflammatory gastrointestinal disease to being obesity. The specification defines the term “prevent” as “the reduction to a lesser degree of the risk or of the probability of occurrence of a given phenomenon” [0069], and defines the term “treat” as “includ[ing] alleviation of the symptoms associated with a specific disorder or condition and/or elimination of said symptoms” [0070].
So, the breadth of the claims require that each of the bacterial strains, individually or together, be able to reduce the risk of or alleviate symptoms of a broad range of diseases.
The existence of working examples: The working examples teach that both P. distasonis CNCM I-5576 and CNCM I-5578 prevent loss of epithelial barrier integrity (see Example 1 beginning [0181], and also Example 3 beginning [0189] and Figure 4D). The working examples teach that both P. distasonis CNCM I-5576 and CNCM I-5578 have anti-inflammatory properties, both in an in vitro model (Example 2 beginning [0184]) and in a murine model of TNBS-induced colitis (Example 3 beginning [0189]). The working examples also teach that CNCM I-5578 can reduce weight gain and other signs and symptoms in a mouse model of obesity (Example 5 beginning [0203]). The working examples also teach that live and heat-killed CNCM I-5576 and CNCM I-5578 have the same (no significant difference in) anti-inflammatory effects (Example 4 beginning [0201]).
The examples show that the probiotics treated the colitis model by reducing the disease’s signs and symptoms (Figures 3-4), but does not disclose that the risk or probability of colitis was reduced in the treated mice so it does not teach preventing colitis. Similarly, the examples show that CNCM I-5588 treated the obesity mouse model by reducing disease’s signs and symptoms but does not test whether CNCM I-5576 has any effect on obesity and does not disclose that the risk or probability of obesity was reduced so it does not teach preventing obesity.
In summary, the working examples show both bacteria have anti-inflammatory effects, and that specific diseases can be treated by the bacteria: leaky gastrointestinal mucosal barrier, colitis, obesity (by CNCM I-5588 only). However, the examples do not show prevention of the diseases because they do not discuss the risk of developing the diseases.
The amount of direction provided by the inventor and the state of the prior art: The inventor repeatedly points out that the effects seen are strain-specific and cannot be generalized to the full species based on the results seen in one strain [0039, 0088].
The specification states that many inflammatory diseases “still have no treatment or have no appropriate treatment” [0007]. The specification teaches that “alterations in microbiota composition together with reduced bacterial diversity, known as dysbiosis, are frequently observed in patients suffering from a variety of chronic disorders including inflammatory bowel disease (IBD) … [and] obesity … However, it remains difficult to establish a definitive causal role of the gut microbiota to such diseases.” [0017], and “consensus about specific disease-relevant taxa remains weak” [0018]. “ The therapeutic strategies for patients with IBD, mainly based the use of anti-inflammatory and/or immunosuppressive drugs are not curative and in addition, about 25-30% of patients fail to respond and 20% of the patients will discontinue therapy due to side-effects” [0018], and although probiotics have been shown to have immune regulatory epithelial barrier strengthening responses [0020], “data are insufficient to recommend probiotics for use in Crohn's disease” [0020] and there is “low effectiveness” [0021]. Therefore, the specification teaches an anti-inflammatory effect or epithelial barrier strengthening effect per se is insufficient to give a reasonable expectation of success at treating IBD given the known issues with current anti-inflammatory therapies and current probiotics.
The specification cites numerous studies in [0016-0021] to support their position, and a review of the art at the time of filing does not find references that disagree with applicant’s summary of the state of the field of treating and preventing these diseases.
The level of predictability in the art: The level of predictability is low given the strain-specific nature of the observed effects and the known drawbacks of other therapies that have been shown to strengthen the intestinal barrier and have anti-inflammatory effects.
The nature of the invention and the quantity of experimentation needed to make or use the invention: The standard of an enabling disclosure is not the ability to make and test if the invention works but one of the ability to make and use with a reasonable expectation of success and without undue experimentation. A patent is granted for a completed invention, not the general suggestion of an idea (MPEP 2164.03 and Chiron Corp. v. Genentech Inc., 363 F.3d 1247, 1254, 70 USPQ2d 1321, 1325-26 (Fed. Cir. 2004). The instant specification is not enabling because one cannot follow the guidance presented therein, or within the art at the time of filing, and practice the claimed method without first making a substantial inventive contribution.
Given that the nature of the invention requires in vivo prevention and treatment of a variety of diseases by either bacteria, a person having ordinary skill in the art would have to perform multiple further in vivo experiments in human clinical trials or in animal models that are predictive of prevention and treatment in a representative number of gastrointestinal diseases and disorders associated with gastrointestinal diseases in order to demonstrate the invention could be used with a reasonable expectation of success. The existing data showing anti-inflammatory effect and improved gastrointestinal epithelial barrier cannot be extended to disease prevention or treatment with a reasonable expectation of success due to the applicant’s own admission that other probiotics with the same effects have had “low effectiveness” [0021].
The amount of experimentation required for enabling guidance, commensurate in scope with what is claimed, goes beyond what is considered ‘routine' within the art, and constitutes undue further experimentation in order to use the method with a reasonable expectation of successfully preventing and treating a representative number of gastrointestinal diseases and disorders associated with gastrointestinal diseases. However, there is a reasonable expectation of achieving an anti-inflammatory effect, improving the gastrointestinal epithelial barrier, and treating colitis using either strain, and of treating obesity with CNCM I-5588. Therefore, claims 17-31 are rejected under 35 U.S.C. §112(a) or 35 U.S.C. §112, first paragraph, for failing to meet the enablement requirement.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 32-35 are rejected under 35 U.S.C. 101 because the claimed invention is directed to natural products without significantly more.
Regarding claims 32 and 34, claim 32 recites a bacterial strain deposited with the CNCM under accession number CNCM I-5576, and claim 34 recites a bacterial strain deposited with the CNCM under accession number CNCM I-5578. The instant specification provides evidence that these strains are natural isolates originating in newborn fecal samples [Table 1, 0167], and does not teach that the strains have been modified in any way relative to the natural product bacteria found in the newborn feces. So, the deposited strains are both natural products.
This judicial exception is not integrated into a practical application because the claims are drawn to the bacteria itself; there are no additional elements. The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the claims are drawn to the bacteria itself; there are no additional elements.
Regarding claims 33 and 35, the claims each recite a composition comprising, in a physiologically acceptable medium, at least the bacterial strains of 32 and 34, respectively. The specification states that the pharmaceutically acceptable medium can include water [0077]. The newborn feces are a natural product that comprises both the bacterial strains and water, as feces are not dry. Also, see MPEP 2106.04(c): “In Myriad, the Supreme Court made clear that not all changes in characteristics will rise to the level of a marked difference, e.g., the incidental changes resulting from isolation of a gene sequence are not enough to make the isolated gene markedly different. … The Supreme Court concluded that these isolated but otherwise unchanged genes were not eligible, because they were not different enough from what exists in nature to avoid improperly tying up the future use and study of the naturally occurring BRCA genes. See, e.g., Myriad, 569 U.S. at 585, 106 USPQ2d at 1977”. Like the genes of Myriad, the isolated bacteria are not changed by virtue of being in a pharmaceutically acceptable medium instead of in feces, so the bacteria and water composition does not have markedly different products. Therefore, the composition combining both bacteria and water recites a natural product.
This judicial exception is not integrated into a practical application because the claims are drawn to the composition itself; there are no additional elements. The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the claims are drawn to the composition itself; there are no additional elements.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to AMELIA NICOLE DICKENS whose telephone number is (571)272-0381. The examiner can normally be reached M-R 8:30-4:30, and every other F 8:30-4:30 (EDT/EST).
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Gary Nickol can be reached at (571)272-0835. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/AMELIA NICOLE DICKENS/Examiner, Art Unit 1645
/GARY B NICKOL/Supervisory Patent Examiner, Art Unit 1645