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 .
Status of Claims
The preliminary amendment filed on 10/27/2023 amended claims 11 and 12 and added new claim 14. There are no claims withdrawn and no claims cancelled. Claims 1-14 are pending and will be examined on the merits.
Priority
Acknowledgment is made of applicant’s claim for foreign priority under 35 U.S.C. 119 (a)-(d). The certified copy has been filed in parent Application No. KR10-2021-0054315, filed on 4/27/2021.
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Information Disclosure Statement
The Information Disclosure Statements filed on 10/27/2023 and 11/22/2024 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the IDSs have been considered by the examiner. Signed copies are enclosed.
The listing of references in the specification starting in paragraph 3 is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
Objections to the Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code in paragraphs 80 and 112. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
The use of the terms such as WITEPSOL, TWEEN, TRIZOL, ACCUPOWER, and more, which are a trade name or a mark used in commerce, has been noted in this application in paragraphs 68, 150, and more. The terms should be accompanied by the generic terminology; furthermore, the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term. Applicant is required to check the remaining specification for all trademark compliance and make appropriate corrections where needed.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
Drawings
The drawings are objected to because:
Figure 1 contains a sequence but is not identified as a sequence number (see below)
Figures 2-4 are not clear enough to provide support for the specification
Figure 16 has mislabeled 16(c) and does not include 16(d), which is referenced in the specification
Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
In addition to Replacement Sheets containing the corrected drawing figure(s), applicant is required to submit a marked-up copy of each Replacement Sheet including annotations indicating the changes made to the previous version. The marked-up copy must be clearly labeled as “Annotated Sheets” and must be presented in the amendment or remarks section that explains the change(s) to the drawings. See 37 CFR 1.121(d)(1). Failure to timely submit the proposed drawing and marked-up copy will result in the abandonment of the application.
Nucleotide and/or Amino Acid Sequence Disclosures
REQUIREMENTS FOR PATENT APPLICATIONS CONTAINING NUCLEOTIDE AND/OR AMINO ACID SEQUENCE DISCLOSURES
Items 1) and 2) provide general guidance related to requirements for sequence disclosures.
37 CFR 1.821(c) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.821(a) must contain a "Sequence Listing," as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.821 - 1.825. This "Sequence Listing" part of the disclosure may be submitted:
In accordance with 37 CFR 1.821(c)(1) via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter "Legal Framework") as an ASCII text file, together with an incorporation-by-reference of the material in the ASCII text file in a separate paragraph of the specification as required by 37 CFR 1.823(b)(1) identifying:
the name of the ASCII text file;
ii) the date of creation; and
iii) the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(1) on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation-by-reference of the material in the ASCII text file according to 37 CFR 1.52(e)(8) and 37 CFR 1.823(b)(1) in a separate paragraph of the specification identifying:
the name of the ASCII text file;
the date of creation; and
the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(2) via the USPTO patent electronic filing system as a PDF file (not recommended); or
In accordance with 37 CFR 1.821(c)(3) on physical sheets of paper (not recommended).
When a “Sequence Listing” has been submitted as a PDF file as in 1(c) above (37 CFR 1.821(c)(2)) or on physical sheets of paper as in 1(d) above (37 CFR 1.821(c)(3)), 37 CFR 1.821(e)(1) requires a computer readable form (CRF) of the “Sequence Listing” in accordance with the requirements of 37 CFR 1.824.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed via the USPTO patent electronic filing system as a PDF, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the PDF copy and the CRF copy (the ASCII text file copy) are identical.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed on paper or read-only optical disc, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the paper or read-only optical disc copy and the CRF are identical.
Specific deficiencies and the required response to this Office Action are as follows:
Specific deficiency – Nucleotide and/or amino acid sequences appearing in the drawings are not identified by sequence identifiers in accordance with 37 CFR 1.821(d). Sequence identifiers for nucleotide and/or amino acid sequences must appear either in the drawings or in the Brief Description of the Drawings.
Required response – Applicant must provide:
Replacement and annotated drawings in accordance with 37 CFR 1.121(d) inserting the required sequence identifiers;
AND/OR
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required sequence identifiers into the Brief Description of the Drawings, consisting of:
A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
A copy of the amended specification without markings (clean version); and
A statement that the substitute specification contains no new matter.
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.
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 2 and 11-14 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.
The term “"a 16S rRNA base sequence"” in claim 2 is ambiguous, which renders the claim indefinite. Bacterial strains do not have more than one 16s rRNA sequence. By referring to the 16.
The term “immunity-enhancing” in claims 11-13 and “enhancing immunity” in claim 14 are relative terms which render the claims indefinite. The term “immunity-enhancing” 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 does not provide a specific definition or definite parameters for "immunity-enhancing" or "enhancing immunity". Paragraphs [47]-[63] provide examples of ‘immunity-enhancing efficacy’, but there is no presented definition for how many of these examples are necessary to consider a composition to be “immunity-enhancing”, nor does it provide any parameters for assessing “enhancing immunity” outcomes.
Additionally, the specification does not provide a subject to which immunity is enhanced. Immunity is defined in the instant specification as “a state where upon generation of specific cells or other substances, such as microorganisms and tissues of the same species, that invade the human body from outside, the ability to produce antibodies is exhibited by recognizing the same as antigens with the involvement of the immune system and reacting specifically thereto to maintain homeostasis of individuals” (emphasis added). Taken with the colloquial definition of immunity as “the state or quality of being resistant to a particular infectious disease or pathogen” (Oxford Languages), immunity requires a subject, as it is a state of being resistant to a specific pathogen. As such, the defining properties of the pharmaceutical composition of claim 11 and the food composition of claims 12 and 13 are undefined and indefinite. Additionally, the method of claim 14 is indefinite, as there are no parameters to define the success of "enhancing immunity", nor a subject the “enhancing immunity” is toward.
Furthermore, as the subject of the enhanced immunity of claim 14 is undefined, the term “a subject in need thereof” in claim 14 is a relative term which renders the claim indefinite. The term “a subject in need thereof” 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. Without a subject of immunity to be enhanced, one cannot determine who a subject in need thereof is, and therefore cannot administer the method for enhancing immunity of claim 14.
For the purposes of this Office Action, the examiner will be interpreting “a subject in need thereof” in light of the specification, which discloses in paragraphs [46], [66], and [71], that the strain “may be used for preventing or treating cancer.” Therefore, for the purposes of evaluating the merits of claim 14, “a subject in need thereof” will be interpreted as a subject in need of preventing or treating cancer.
112 (a) Rejections
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.
Claim 14 is rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention. This is a written description rejection.
Claim 14, drawn to a method for enhancing immunity, the method comprising administering an L. fermentum ATG-V5 strain deposited under accession number KCTC14481BP to a subject in need thereof. This claim will be interpreted as set out above. This claim of using L. fermentum to enhance immunity to prevent or treat cancer, where the scope of the claim encompasses the list of cancers in the specification, does not meet the written description requirement of U.S.C. 112(a).
The specification discloses “a Lactobacillus fermentum ATG-V5 strain [with] no cytotoxicity and…the following immunity-enhancing efficacies: increasing secretion amounts of nitric oxide (NO), interleukin 6 (IL-6), and tumor necrosis factor (TNF) in macrophages, enhancing phagocytosis, reducing a secretion amount of interleukin 1β (IL-1β) in macrophages, enhancing cell viability of splenocytes, increasing secretion amounts of antibodies and cytokines in the blood, and the like” (paragraph [10]). The specification also discloses that “[t]he strain having the immunity-enhancing efficacy may be used for preventing or treating cancer. Such cancers may include at least one selected from the group consisting of breast cancer, colorectal cancer, lung cancer, small cell lung cancer, stomach cancer, liver cancer, blood cancer, bone cancer, pancreatic cancer, skin cancer, head or neck cancer, skin or intraocular melanoma, uterine cancer, ovarian cancer, rectal cancer, anorectal cancer, colon cancer, fallopian tube carcinoma, endometrial carcinoma, cervical cancer, vaginal cancer, vulvar carcinoma, Hodgkin's disease, esophageal cancer, small intestine cancer, endocrine gland cancer, thyroid cancer, parathyroid cancer, adrenal cancer, soft tissue sarcoma, urethral cancer, penile cancer, prostate [cancer], chronic or acute leukemia, lymphocytic lymphoma, bladder cancer, kidney cancer, ureteral cancer, renal cell carcinoma, renal pelvic carcinoma, CNS tumor, primary CNS lymphoma, spinal cord tumor, brainstem glioma, and pituitary adenoma” (paragraphs [46], [66], and [71]).
Example 3 (starting paragraph [119]) of the specification teaches a response from the representative macrophage cell line RAW 264.7 when the recited strain is added to the cell culture. Example 4 (starting paragraph [136]) teaches oral administration of bacterial cells from the recited strain to mice with cyclophosphamide (CPP)-induced immunosuppression and the subsequent measured immune response in said CPP-treated mice. The specification teaches that “cyclophosphamide (CPP) is an anticancer drug widely used for all types of cancers, sarcomas, leukemia, and malignant lymphoma, and is a non-specific immunosuppressant” (paragraph [138]).
The L. fermentum ATG-V5 strain deposited under accession number KCTC14481BP, and the administration of this strain to a mouse receiving CPP treatment, meets the written description provision of 35 U.S.C. 112(a). However, the specification does not support the claims of “enhancing immunity” or the claims of “a subject in need thereof” when the subject is interpreted broadly as a subject in need of cancer treatment or prevention.
As stated above, immunity is a state of protection against a specific pathogen. While the specification clearly demonstrates an enhanced immune response after administration of the claimed strain to a mouse treated with CPP (Example 4), there is no evidence that this response is protective against any pathogen. Without any experimentation demonstrating protection upon challenge with a pathogen, any claim of “enhanced immunity” is not considered to be supported.
The claims of “preventing or treating cancer” are also unsupported. The term “preventing” is defined as “keep (something) from happening or arising” (Oxford Languages), while the term “treating” indicates the alleviation of symptoms, for example, once the cancer has been established. Additionally, cancers are known to be varied and specific to their host. Thus, the claim of “preventing or treating cancer”, especially in the light of the provided list of cancers, indicates a very broad genus of claims towards preventing the establishment of, or treating symptoms of, an established disease. There is no evidence in the specification that the administration of the strain has any effect on either the development or treatment progression of any cancer, let alone the list of cancers provided. Therefore, the specification is not deemed sufficient to reasonably convey to one skilled in the art that the inventors, at the time the invention was made, had possession of a method of enhancing immunity comprising administering the claimed strain to a subject in need thereof because no evidence is presented to support the claims of enhanced immunity or preventing or treating cancer.
Vas-Cath Inc. v. Mahurkar, 19 USPQ2d 1111, makes clear that "applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the 'written description' inquiry, whatever is now claimed." (See page 1117.) The specification does not "clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed." (See Vas-Cath at page 1116.)
The state of the art regarding the intersection between cancer and probiotic treatments is explored in Abedin-Do et al. (Immunotherapy (2015) 7(12), 1307-1329). Abendin-Do et al. teach that Lactobacillus species can have a variety of effects on the immune system in the context of cancer treatment (Box 1). However, these effects differ depending on the models used, and the authors caution that the majority of the studies on the link between probiotic administration and cancer treatment have been performed in animal models, and that the translation of these studies into human clinical trials is lacking (Abendin-Do, abstract and page 1316, right column).
The art of “treating” cancer with Lactobacilli in humans is limited. At best, most studies have been performed with the Lactobacilli being administered concomitantly with another cancer treatment. The administration of probiotic strains has been shown to have synergistic effects with a cancer treatment, but has not been shown to completely replace the treatment, indicating that, at best, Lactobacilli augment cancer treatment, and do not treat cancer themselves (Asoudeh-Fard et al., Cancer Cell International (2025) 25:389; Renukadevi et al., J. Bio-X Res. (2025); 8: Article 0028).
In terms of “preventing” cancer, while some studies claim to show that Lactobacilli have effects that could lessen cancer development (Ghorbani et al., Nutrition 103-104 (2022) 111828), other studies show an increase in cancers when Lactobacilli are present at increased levels (Li et al. World Journal of Gastrointestinal Oncology vol. 13,9 (2021): 1099-1108). Thus, the art is divided on the ability of Lactobacilli to prevent cancer, with only correlations demonstrated at best.
Additionally, it is known in the art that cancer cells arising from different tissues differ in etiology and response to treatment. Heppner et al. (Cancer Metastasis Review 2:5-23; 1983) discuss the heterogeneity of tumors from different tissues, as well as the same tissue. A key point made by Heppner et al. is that tumor heterogeneity contributes greatly to the sensitivity of tumors to drugs. Heppner et al. teach that as a tumor progresses to a metastatic phenotype, the susceptibility to a particular treatment can differ, and as such, makes predicting the responsiveness to treatment difficult.
Taken together, the prior art establishes that the treatment or prevention of cancer with probiotics like L. fermentum is poorly understood, as most studies have been performed in animal models and do not translate well to other species. Additionally, a majority of studies have been performed by administering probiotics alongside known cancer treatment, indicating that the alleviation of any symptoms cannot be prescribed to the probiotic organism. The art is silent in regards to the broad application of probiotics to treating or preventing all cancers; in contrast, the art of cancer treatment indicates that cancers of different types and tissues are highly variable in their response to any treatment. Accordingly, one skilled in the art would conclude that the claimed invention encompasses a broad genus of preventing and treating cancers that may or may not respond to treatment with probiotics. It should be noted that the specification has not demonstrated treating even a single species of cancer. While the prior art demonstrates probiotics may be effective in preventing some cancers, one skilled in the art would not deem the prior art in cancer treatment to be predicative of the efficacy of one strain “preventing or treating” such broad cancers. Additionally, the majority of studies on the effectiveness of probiotic treatment on cancers have been performed in animal models (primarily mice), and the art acknowledges that the translation of these results to a human or other mammalian model would be highly unpredictable. Thus, based on the teachings of the instant specification and the prior art, one skilled in the art would not conclude that Applicant was in possession of the claimed method of treating or preventing cancer with a probiotic L. fermentum strain.
Consequently, the method of claim 14, for enhancing immunity…in a subject in need thereof, does not meet the written description provision of 5 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph. The applicant has not disclosed any evidence to support the claim of “enhancing immunity.” Additionally, when ‘a subject in need thereof’ is interpreted in light of the specification, the applicant has not disclosed “preventing or treating” any species representative of the genus of cancers, which is highly variant. Applicant is reminded that Vas-Cath makes clear that the written description provision of 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, is severable from its enablement provision. (See page 1115).
Biological Deposit Requirement
Claims 1-14 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the enablement requirement. The claims contain 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 Lactobacillus fermentum ATG-V5 strain represented by the KCTC accession number 14481BP is required in order to practice the invention. Specifically, it is noted that claim 1 recites deposited material and that claims 2-14 depend from claims reciting deposited material. The deposit of biological organisms is considered by the Examiner to be necessary for the enablement of the current invention (see 37 CRF 1.808(a)). The Examiner acknowledges the deposit of organisms under the KCTC accession number 14481BP in partial compliance with this requirement. However, said deposits are not in full compliance with 37 CFR 1.803-1.809, as they do not contain a statement that all availability restrictions will be irrevocably removed upon the granting of a patent.
If the deposit is made under terms of the Budapest Treaty, then an affidavit or declaration by Applicants or person(s) associated with the patent owner (assignee) who is in a position to make such assurances, or a statement by an attorney of record over his or her signature, stating that the deposit has been made under the terms of the Budapest Treaty and that all restrictions imposed by the depositor on the availability to the public of the deposited material will be irrevocably removed upon the granting of a patent, would satisfy the deposit requirements. See 37 CFR 1.808.
If a deposit is not made under the terms of the Budapest Treaty, then an affidavit, or declaration by Applicants or person(s) associated with the patent owner (assignee) who is in a position to make such assurances, or a statement by an attorney of record over his or her signature, stating that the following criteria have been met:
1) during the pendency of the application, access to the deposit will be afforded to one determined by the Commissioner to be entitled thereto;
2) all restrictions imposed by the depositor on the availability to the public of the deposited material will be irrevocably removed upon the granting of a patent; and
3) the deposits will be maintained for a term of at least thirty (30) years from the date of the deposit or for the enforceable life of the patent or for a period of at least five (5) years after the most recent request for the furnishing of a sample of the deposited material, whichever is longest; and
4) a viability statement in accordance with the provisions of 37 CFR 1.807; and
5) the deposit will be replaced should it become necessary due to inviability, contamination or loss of capability to function in the manner described in the specification.
In addition, the identifying information set forth in 37 CRF 1.809(d) should be added to the specification. Specifically, the address of the depository is not stated in the specification. See 37 CFR 1.803 – 1.809 for additional explanation of these requirements.
Based on these requirements, to satisfy the biological deposit requirements, a statement that affirms that all restrictions imposed by the depositor on the availability to the public of the deposited material will be irrevocably removed upon the granting of a patent should be submitted, and the specification should be amended to state the address of the depository alongside the information provided in paragraphs [158]-[161].
112(d) Improper Dependent Claims
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.
Claims 2-9 are 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. Claims 2-9 describe inherent properties of the ATG-V5 strain of claim 1, and thus impose no further limitations on claim 1. Applicant may cancel the claims, amend the claims to place the claims in proper dependent form, rewrite the claims in independent form, or present a sufficient showing that the dependent claims comply with the statutory requirements.
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 1-13 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a product of nature without significantly more. The claims recite a Lactobacillus fermentum ATG-V5 strain with no modifications made to the organism. This reads on a "product of nature". As stated by the Applicant in the specification, paragraph [78], the bacteria were isolated from hallabong obtained from Jeju Island. Claim 2 merely states a 16S rRNA sequence with no variation from the naturally occurring sequence, and claims 3-9 describe inherent properties exhibited by the unmodified naturally occurring organism. This judicial exception is not integrated into a practical application because merely claiming the properties of an naturally occurring organism does not add a meaningful limitation to the claims. The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception because nothing more than the naturally occurring organism is claimed. Claim 10 recites the additional elements of culture media (necessary to cultivate the organism), metabolites, and dead cells, which are by-products of the organisms' growth. Claim 11 recites a pharmaceutical composition, but does not require the composition to have any components other than the naturally occurring organism. Similarly, claims 12 and 13 recite a food composition but do not require the food composition to have any components other than the naturally occurring organism.
Claim Rejections - 35 USC § 102/103
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.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
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.
Section 2112.III of the MPEP states:
“A rejection under 35 U.S.C. 102 and 103 can be made when the prior art product seems to be identical except that the prior art is silent as to an inherent characteristic. Where applicant claims a composition in terms of a function, property or characteristic and the composition of the prior art is the same as that of the claim but the function is not explicitly disclosed by the reference, the examiner may make a rejection under both 35 U.S.C. 102 and 103. "There is nothing inconsistent in concurrent rejections for obviousness under 35 U.S.C. 103 and for anticipation under 35 U.S.C. 102." In re Best, 562 F.2d 1252, 1255 n.4, 195 USPQ 430, 433 n.4 (CCPA 1977). This same rationale should also apply to product, apparatus, and process claims claimed in terms of function, property or characteristic. Therefore, a 35 U.S.C. 102 and 103 rejection is appropriate for these types of claims as well as for composition claims.”
Claims 1-14 is/are rejected under 35 U.S.C. 102(a)(1) as anticipated by or, in the alternative, under 35 U.S.C. 103 as obvious over "Evaluation of the Immunomodulatory Activities of the Probiotic Strain Lactobacillus fermentum UCO-979C", Valeria Garcia-Castillo et al., Frontiers in Immunology, 13 June, 2019 (hereinafter Garcia-Castillo).
The instant application claims an L. fermentum strain with a 16S rRNA base sequence of SEQ ID NO: 1, which elicits an enhanced immune response, including increases in NO secretion and phagocytosis by macrophages, enhanced cytotoxicity of NK cells, enhanced cell viability of splenocytes, increased T cell differentiation, and increased secretion amounts of antibodies and cytokines in the blood.
Garcia-Castillo teaches a probiotic L. fermentum strain UCO-979C with 16S rRNA sequence of SEQ ID NO: 1, thereby matching the limitations of claim 2 (pg 2 right column). The strain of Garcia-Castillo teaches increased phagocytic activity and respiratory burst in macrophages, meeting the limitations of claims 3 and 4 (pg 5 left column and figure 4). Garcia-Castillo also teaches an increase in IgA (pg 5, left column and Figure 4) and IL-10 (pg 5 right column and figures 5 and 6), meeting the limitations of claims 8 and 9. Garcia-Castillo teaches increases in T-cell populations in Peyer’s patches, and minimal further testing of these populations is likely to expose increases in Th1, 2, 17, or Treg cells, thereby meeting the limitations of claim 7 (pg 6, left column and figure 9). Additionally, Garcia-Castillo teaches the growth of the strain in culture media, teaching claim 10 (pg 2, right column).
Claim 11 of the instant application teaches a pharmaceutical composition comprising the instant strain, while claims 12 and 13 teach a food composition comprising the instant strain. Garcia-Castillo teaches administering or feeding the probiotic strain UCO-979C to the mice orally by adding bacteria to drinking water (pg 3 right column), thereby meeting the pharmaceutical composition taught by claim 11 and the food composition taught by claims 12 and 13.
Regarding instant claim 14, which is drawn to ‘a method of enhancing immunity comprising administering the ATG-V5 strain of claim 1 to a subject in need thereof’, Garcia-Castillo teaches that “The feeding of mice with L. fermentum UCO-979C significantly increased the production of intestinal IFN-γ, stimulated intestinal and peritoneal macrophages and increased the number of Peyer’s patches CD4+ T cells (abstract)”, thereby indicating the administration of the L. fermentum strain to a subject in need thereof, resulting in ‘enhanced immunity’, as stated in claim 14.
As it appears the strain of Garcia-Castillo has the same characteristics of the claimed strain, any further attributes not described in Garcia-Castillo would be inherently present (such as increased NK cell cytotoxicity and splenocyte viability). As stated in the MPEP 2112.01, “Product and apparatus claims – when the structure recited in the reference is substantially identical to that of the claims, claimed properties or functions are presumed to be inherent. Where the claimed and prior art products are identical or substantially identical in structure or composition, or are produced by identical or substantially identical processes, a prima facie case of either anticipation or obviousness has been established. In re Best, 562 F.2d 1252, 1255, 195 USPQ 430, 433 (CCPA 1977). "When the PTO shows a sound basis for believing that the products of the applicant and the prior art are the same, the applicant has the burden of showing that they are not." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). Therefore, the prima facie case can be rebutted by evidence showing that the prior art products do not necessarily possess the characteristics of the claimed product. In re Best, 562 F.2d at 1255, 195 USPQ at 433. See also Titanium Metals Corp. v. Banner, 778 F.2d 775, 227 USPQ 773 (Fed. Cir. 1985).” “Composition claims – if the composition is physically the same, it must have the same properties. “Products of identical chemical composition can not have mutually exclusive properties.” In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present. Id.”
Therefore, since the strain of L. fermentum described by Garcia-Castillo has every claimed attribute of the instant strain, and as strain names can be granted at the purview of the publishing entity and accession numbers are granted upon receipt at a depository, there is no reason to believe the strain of Garcia-Castillo is different from the instant strain in the application. Consequently, Garcia-Castillo anticipates the invention as claimed.
In the alternative, the previously mentioned strain of Garcia-Castillo has the 16S rRNA sequence of the instant strain and triggers an enhanced immune response with necessarily the same characteristics, including eliciting an enhanced macrophage response, increased cytokine production, increased T cell populations, and increased antibody production. Therefore, one of ordinary skill in the art would reasonably conclude that the instant strain is an obvious variant of Garcia-Castillo based on the aforementioned characteristics. Thus, the claimed invention, as a whole, is prima facie obvious in view of the teaching of Garcia-Castillo, absent any convincing evidence to the contrary, regarding the obvious variants of L. fermentum strain UCO-979C and ATG-V5.
Conclusion
Claims 1-14 are rejected. No claim is allowed.
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure. “In vitro immunomodulatory activity of Lactobacillus fermentum CECT5716 and Lactobacillus salivarius CECT5713: two probiotic strains isolated from human breast milk”, Perez-Cano et al., Immunobiology, 2010. Perez-Cano discloses L. fermentum strain CECT5716 with immunomodulatory effects, including increased NK cell proliferation and activity, increased splenocyte proliferation, expansion of Treg cells, and increases in IL-2, IL-6, and IL-10.
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/AMELIA STEPHENS/ Examiner, Art Unit 1645
/VANESSA L. FORD/ Supervisory Patent Examiner, Art Unit 1674
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