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 .
The substitute specification filed 3-28-2024 has been entered into the record. The response filed 3-26-2026 has been entered into the record. Claims 1-15 are pending.
Priority
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Election/Restrictions
Applicant’s election of Group I claims 1-9 and 14 in the reply filed on 3-26-2026 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)). Claims 10-13 and 15 are withdrawn from consideration.
Information Disclosure Statement
The information disclosure statement has been considered. An initialed copy is enclosed.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
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(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.
Claims 1-9 and 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 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.
The claims are drawn to a strain of Enterococcus faecium LCM001, culture medium or cell free supernatant of the strain as an active ingredient or as an active ingredient of a health functional food administered to a subject for preventing or treating cancer in view of its apoptotic effect and gene-expression inhibition on cancer cells in vitro. Other than generic guidelines for formulating pharmaceutical compositions and functional foods, the specification lacks any particular information regarding on routes of administration of the bacterium, culture medium or cell free supernatant to any in vivo cancer model that reasonably correlates with prevention and treatment of spontaneous cancer in a subject or provides the apoptotic or gene inhibitory effects in vivo as claimed. No specifics are described regarding dosing timing, route of dosing, the amount (CFU) of bacteria or culture supernatant to be fed or administered is provided. No evidence is provided that cancer can be prevented by administering or feeding to an animal or subject having or susceptible to cancer. No long-term studies have been provided to demonstrate for when and how long the claimed compositions need to be administered to prevent or treat spontaneous cancers in general or the specific cancers enumerated. Applicant has not demonstrated that the in vitro test results reasonably correlate with in vivo results for the prevention and treatment of cancer with functional foods in particular. Absent a reasonable in vitro-in vivo correlation, the skilled artisan would be unable to translate the results to a successful treatment or prevention as claimed. The art teaches that drug screening remains an empirical one, as compounds are prioritized for development on the definition of anti-proliferative in vitro and in vivo responses. In vitro activities are evaluated against in vivo models (see Johnson et al (British Journal of Cancer 84(10):1424-1431, 2001) at page 1424, column 2, second and third paragraphs. Clinical activity cannot be assumed from in vitro test results. Huber et al (Journal of Pharmacokinetics and Pharmocodynamics 51:169-185, 2024) teach that it is crucial to establish the translatability of results from simple in vitro systems to more complex in vivo systems. This translatability is essential for interpreting study outcomes, designing experiments and enabling studies in higher species. In order to address this need, the use of in-vitro to in vivo correlation studies is necessary. The studies establish a relationship between a specific aggregated in vitro parameter and drug exposure to explain a particular-drug induced effect (see 169, column 2, second paragraph). The instant specification lacks the fundamental in vitro-in-vivo correlation studies in order to demonstrate the most basic clinical activity. Absent the correlative studies, the skilled artisan would be unable to reasonably predict which cancers and which fractions, administered by which routes would be effect. In order to determine such, the skilled artisan would have to select animal models of cancer, determine dosages, determine routes of administration, determining timing and spacing of dosing in the animal models to determine if the bacteria, culture medium or cell-free supernatant has potential clinical activity in vivo. These activities require ingenuity beyond that to be expected by one of ordinary skill in the art. The specification is merely an invitation to experiment to determine if the bacterium, culture medium or cell-free supernatants can be used as claimed as they have not established the basic in vitro-in vivo correlation for basic clinical testing. The courts have held ”… in cases involving unpredictable factors, such as most chemical reactions and physiological activity, scope of enablement varies inversely with degree of unpredictably of factors involved." (In re Fisher 166 USPQ 18 (CCPA)) and hat the disclosure is insufficient when testing is necessary to determine the actual use or possible lack of use (In re Kirk and Petrow 153 USPQ 48 (CCPA 1967). For the foregoing reasons, it would require undue experimentation to determine if the claimed bacterium, culture medium or cell-free supernatants can be used in the manner described for all the reasons set forth herein.
Finally, the specification lacks complete deposit information for the deposit of Enterococcus faecium LCM001 strain and paragraph [112]. Because it is not clear that cell lines possessing the properties of LCM001 are known and publicly available or can be reproducibly isolated from nature without undue experimentation and because the best mode disclosed by the specification requires the use of LCM001, a suitable deposit for patent purposes is required. Accordingly, filing of evidence of the reproducible production of the cell line claimed in claims 1-9 and 14 is required. Without a publicly available deposit of the above cell line, one of ordinary skill in the art could not be assured of the ability to practice the invention as claimed. Exact replication of the cell line is an unpredictable event.
Applicant's referral to the deposit of the bacterial species at paragraphs [57] and [112] of the specification is an insufficient assurance that all required deposits have been made and all the conditions of 37 CFR §1.801-1.809 have been met.
If the deposit has been made under the provisions of the Budapest Treaty, filing of an affidavit or declaration by applicant or assignees or a statement by an attorney of record who has authority and control over the conditions of deposit over his or her signature and registration number stating that the deposit has been accepted by an International Depository Authority under the provisions of the Budapest Treaty, that all restrictions upon public access to the deposit will be irrevocably removed upon the grant of a patent on this application and that the deposit will be replaced if viable samples cannot be dispensed by the depository is required. This requirement is necessary when deposits are made under the provisions of the Budapest Treaty as the Treaty leaves this specific matter to the discretion of each State. Amendment of the specification to recite the date of deposit and the complete name and full street address of the depository is required.
If the deposits have not been made under the provisions of the Budapest Treaty, then in order to certify that the deposits comply with the criteria set forth in 37 CFR §1.801-1.809, assurances regarding availability and permanency of deposits are required. Such assurance may be in the form of an affidavit or declaration by applicants or assignees or in the form of a statement by an attorney of record who has the authority and control over the conditions of deposit over his or her signature and registration number averring:
(a) during the pendency of this application, access to the deposits will be afforded to the Commissioner upon request;
(b) all restrictions upon the availability to the public of the deposited biological material will be irrevocably removed upon the granting of a patent on this application;
(c) the deposits will be maintained in a public depository for a period of at least thirty years from the date of deposit or for the enforceable life of the patent of or for a period of five years after the date of the most recent request for the furnishing of a sample of the deposited biological material, whichever is longest; and
(d) the deposits will be replaced if they should become nonviable or non-replicable.
In addition, a deposit of biological material that is capable of self-replication either directly or indirectly must be viable at the time of deposit and during the term of deposit. Viability may be tested by the depository. The test must conclude only that the deposited material is capable of reproduction. A viability statement for each deposit of a biological material not made under the Budapest Treaty must be filed in the application and must contain:
1) The name and address of the depository;
2) The name and address of the depositor;
3) The date of deposit;
4) The identity of the deposit and the accession number given by the depository;
5) The date of the viability test;
6) The procedures used to obtain a sample if the test is not done by the depository; and
7) A statement that the deposit is capable of reproduction.
As a possible means for completing the record, applicant may submit a copy of the contract with the depository for deposit and maintenance of each deposit.
If the deposit was made after the effective filing date of the application for patent in the United States, a verified statement is required from a person in a position to corroborate that the hybridoma cell line described in the specification as filed is the same as that deposited in the depository. Corroboration may take the form of a showing of a chain of custody from applicant to the depository coupled with corroboration that the deposit is identical to the biological material described in the specification and in the applicant's possession at the time the application was filed.
An international deposited microorganism form RO/134 filed 3-28-2024 is of record but is not in English and therefore cannot be evaluated as to whether the deposit meets the requirements set forth above. Applicant's attention is directed to In re Lundack, 773 F.2d. 1216, 227 USPQ 90 (CAFC 1985) and 37 CFR §1.801-1.809 for further information concerning deposit practice. For all the foregoing reasons, it would require undue experimentation to make and use the claimed invention.
Claims 1-9 and 14 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, or for pre-AIA the applicant regards as the invention.
As to claims 1-9 and 14, the claims recite LCM001 strain (KACC81214BP) and it is unclear if the strain is limited to the specific strain recited in the parenthesis. It is suggested that Applicant amend the claims to recite “…LCM001 strain deposited as KACC81214BP”.
Similarly, in Claim 2, the claim places “[SEQ ID NO:1]” in brackets and it is unclear if the sequence of the rRNA gene is limited to SEQ ID NO:1. Applicant should amend the claim to recite “having a 16S RNA gene sequence as set forth by SEQ ID NO:1” to resolve this issue.
As to claims 3-7, the terms “culture medium or cell free supernatant” lacks antecedent basis in the claims and is prima facie indefinite.
Claims 2-7 are rejected under 35 U.S.C. 112(d), 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. Dependent claims 2-7 recite inherent characteristics of the bacterial strain of claim 1 and therefore do not further limit the scope of the bacterial strain claim 1. 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.
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 1-7 are rejected under 35 U.S.C. 101 because the claimed invention is directed to non-statutory subject matter. The claim(s) does/do not fall within at least one of the four categories of patent eligible subject matter because they claim a natural product without more.
Instant claims 1-7 are drawn to a bacterial product, Enterococcus faecium LCM001 having various properties for various intended uses (apoptopsis, inhibition of gene expression). Because the claimed strain(s) are composed of matter, at least one embodiment encompassed within the broadest reasonable interpretation (BRI) of instant claims is directed to a statutory category, i.e., a product or a composition of matter comprising the product. The as-filed specification at does not document that the bacterium strain of the invention was genetically manipulated in any manner. It is presumed that the claimed strain is isolated from a naturally occurring source, i.e., from nature without genetic manipulation. Therefore, the claimed strain is a naturally occurring strain. There is no evidence that the claimed bacterial strain is modified in any way and such that the strain is markedly different from what exist in nature. Supreme Court has made it clear in Myriad that eligibility requires the creation of something not naturally occurring, which is markedly different from what exists in nature. Unlike the Chakrabarty bacterium, which was new “with markedly different characteristics from any found in nature” Diamond v. Chakrabarty, 447 U.S. 303 (1980) at 310, 100 S. Ct. 2204, 65 L. Ed. 2d 144, due to the multiple additional plasmids and resultant “capacity for degrading oil”, there is no indication that the instantly claimed strain(s) are genetically manipulated or structurally modified in any marked or significant way such that the structural difference results in change of properties of the strain(s). Furthermore, the characteristics set forth in claims 2-7 represent the inherent qualities, properties or characteristics inseparable from said naturally occurring strain(s) and therefore are a handiwork of nature. In Chakrabarty and Myriad, the marked difference inquiry was focused on the modified structural characteristics of the product, not how it was used or how it was made. Note that “….. patents cannot issue for the discovery of phenomena of nature”. Le Roy v. Tatham, 14 How. 156, 175 (1853). The qualities of the bacteria, like the heat of the sun, electricity, or the qualities of metals, are part of the storehouse of knowledge of all men. They are manifestations of laws of nature, free to all men and reserved exclusively to none.” See Funk Brothers Seed Co. v. Kalo Inoculant Co., 333 U.S. at 130, 1948. In Funk Brothers, the Court held that the composition was not patent eligible because the patent holder did not alter the bacteria in any way. In the instant case, indicating that the composition is placing the bacterial strain is present in a pharmaceutical composition, a functional food, a probiotic or animal feed additive does not add significantly more to the natural products such that it is practically applied. There is nothing more than the naturally occurring bacterium present. Thus, each component of the instantly claimed product and composition is a ‘product of nature’ exception, and the claims are directed to a judicial exception. Judicial exceptions include all natural products including those derived from natural sources or patients such as naturally occurring microorganisms, proteins, peptides, glycoproteins, glycopeptides, carbohydrates, and other substances found in or derived therefrom, or from nature. Next, the compositional claims as a whole are analyzed to determine whether any additional element, or combination of elements, is sufficient to ensure that the claims amount to significantly more than the exceptions. Having the naturally occurring strain in a composition as set forth above does not amount to significantly more. There is nothing that provides significantly more or that integrates the claimed naturally occurring strain or said compositions, i.e., the judicial exceptions, into a practical application. No elements or claim limitations apply or use the exception(s) in any meaningful way and integrate the law of nature into a practical application. The claims as a whole do not amount to significantly more than ‘products of nature’. Therefore, the claims are not directed to a patent eligible subject matter.
The rationale for this determination is formed in view of the 2019 PEG, the 2015 Update of the 2014 Interim Guidance on Patent Subject Matter Eligibility (79 FR 4618) (hereafter Interim Eligibility Guidance) dated 16 December 2014, the Life Sciences Examples issued in May 2016, and in view of Myriad v Ambry, CAFC 2014-1361, -1366, 17 December 2014. The unpatentability of laws of nature was confirmed by the U.S. Supreme Court in Mayo Collaborative Services v. Prometheus Laboratories, Inc., No. 10-1150 (March 20, 2012). The unpatentability of natural products was confirmed by the U.S. Supreme Court in Association for Molecular Pathology v. Myriad Genetics, Inc., 569 U. S. (June13, 2013).
Free of the Prior Art
The claims directed to the strain Enterococcus faecium LCM001 deposited as KCTC 14669BP is free of the prior art.
The closest prior art is Mulder et al (US 10,046,015) teaches an E. faecium strain having a 16S rRNA having 98.6% identity as compared to SEQ ID NO:1 herein. Mulder et al teaches strains of E. faecium provide for in vivo data demonstrating oral administration of a pharmaceutical composition provides for a reduction of inflammation associated with Th17 differentiation. Inasmuch as the strains of Mulder et al have not been demonstrated to have an apoptotic effect on cancer cells or that the instant LCM001 has the properties of the ‘015 patent strains the LCM001 strain is free of the prior art.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Patricia Duffy whose telephone number is (571)272-0855. The examiner can normally be reached 8:00 am - 4 pm.
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/Patricia Duffy/Primary Examiner, Art Unit 1645
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