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 .
Claim status
Claims 34-53 are pending following the preliminary amendment filed 04/01/2024. Claims 1-33 are cancelled. Claims 34-53 are presently considered.
Priority
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
The present application and all claims are being examined with the earliest effective filing date of 10/01/2021.
Information Disclosure Statement
The information disclosure statement (IDS) filed 04/01/2024 has been considered by the examiner.
Drawings
The drawings are objected to because:
-Figure 1(a) and 1(c) recite the term “NC”. This abbreviation is not defined in the drawing or in the description of drawings (see specification at pg. 34, para. [121]).
-The shading used to depict the species of BB-JJ in Fig. 1(c) are too similar to one another to be distinguished in the bar graph.
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.
Claim Objections
Claim 34 is objected to because of the following informalities: for clarity, please amend “a subject” in line 2 to recite “a subject in need thereof”. Appropriate correction is required.
Claim 44 is objected to because of the following informalities: for clarity, please amend “a subject” in line 2 to recite “a subject in need thereof”. Appropriate correction is required.
Claim Interpretation
Independent claim 34 recites a “method for preventing or treating an inflammatory disease or cognitive dysfunction” comprising administering bacteria to a subject. Here, the method for “preventing” does not require the subject to have the disease or dysfunction. Hence, the “subject” of claim 34 is interpreted to include any subject.
Independent claim 44 recites a “method for improving immune function” comprising administering bacteria to a subject. The scope of the claim includes subjects having specified conditions, such as immunodeficiency, immunosuppression, or immune system damage (as recited in dependent claim 48) but also includes subjects without these conditions, including subjects with “normal immunity” (see dependent claim 50). Here, a subject having “normal immunity” is reasonably interpreted to be one who does not have an immunodeficiency, immunosuppression, or immune system damage. Hence, the “subject” of claim 44 is interpreted to include any subject having an immune system (i.e., any mammal).
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 35-37 and 45-48 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.
Claims 35-37 and 45-47 recite the limitation, “wherein the [bacterial strain] comprises 16S rDNA sequence of [SEQ ID NO]”. This limitation lacks the use of an article (“a” or “the”) preceding the phrase “16S rDNA sequence of [SEQ ID NO]”. This renders the claims indefinite, because the interpretation of the claims depend on which article is intended, as each may encompass a different scope. For example, a bacterial strain that “comprises the 16S rDNA sequence of SEQ ID NO: 1” comprises the full-length of SEQ ID NO: 1. However, a bacterial strain that “comprises a 16S rDNA sequence of SEQ ID NO: 1” may comprise the full-length of the recited sequence or any portion of the recited sequence (any contiguous sequence of two or more base pairs). Hence, without reciting “a” or “the” before the phrase “16S rDNA sequence of…” the scope of the claim is unclear.
In the interest of compact prosecution, claims 35-37 and 45-47 are given their broadest reasonable interpretation, wherein each recited bacterial strain “comprises a 16S rDNA sequence” of the recited SEQ ID NO.
Claim 48 recites the limitation, “wherein improving immune function is recovering the occurrence of immunodeficiency, immunosuppression, or immune system damage due to radiation therapy or exposure, antibiotic treatment, or anticancer drug treatment.” This renders the claim indefinite, because the meaning of the phrase “recovering the occurrence” is unclear. For example, if “improving immune function” is “recovering the occurrence of immunodeficiency”, then the claim is directed to “a method for recovering the occurrence of immunodeficiency”. Note that the plain meaning of this phrase is that the method causes immunodeficiency to re-occur. However, in contrast to the plain meaning of the claim, a person skill would not reasonably conclude that a method for “improving immune function” would include methods which cause the immunodeficiency to re-occur.
Furthermore, the claim is rendered indefinite due to repeated use of the transition word, “or”. Here the claim follows the form of “A, B, or C due to D, E, or F” where it is unclear whether the limitations of “D, E, or F” are applicable to the limitations of “A” and “B” or are only applicable to the limitation of “C”. In this case, it is unclear whether the “immunodeficiency” or “immunosuppression” are also “due to radiation therapy or exposure, antibiotic treatment, or anticancer drug treatment”, or if only the “immune system damage” is “due to radiation therapy or exposure, antibiotic treatment, or anticancer drug treatment.” Hence, the multiple recitations of the word “or” causes confusion and leads to different interpretations.
In the interest of compact prosecution, claim 48 is interpreted as follows:
“The method of claim 44, wherein the subject is recovering from an occurrence of immunodeficiency, immunosuppression, or immune system damage, wherein the occurrence is due to radiation therapy or exposure, antibiotic treatment, or anticancer drug treatment.”
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.
Claims 35-37 and 45-47 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 35-37 and 45-47 recite the bacterial strains comprising a 16S rDNA sequence according to SEQ ID NOs 1-3. However the parent claims, claims 34 and 44, recite the same strains having an accession number. In view of the instant specification, these accession numbers were given by the depository where these strains have been deposited (see, e.g., pgs. 74-79), and the recited SEQ ID NOs specifically describe the 16S rDNA sequences of the deposited strains, as determined by the inventors (see pg. 42, paras. [148]-[149]). Hence, the deposited bacterial strains of claims 34 and 44 must necessarily comprise these sequences. Therefore, claims 35-37 and 45-47 do not provide any further limitation. Furthermore, the BRI of claims 35-37 and 45-47, as discussed under 35 U.S.C. 112(b), include sequences which are not required to comprise the full length of the recited sequences, thereby improperly broadening the scope of the claims from which they depend.
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.
Applicant may also incorporate the subject matter (i.e., SEQ ID NOs) of the claims above into independent claims 34 and 44.
Claim Rejections - 35 USC § 112(a) – Enablement
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 34-53 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.
Independent claims 34 and 44 recite methods comprising “administering to a subject an effective amount of Lactobacillus rhamnosus NK210 having the accession number KCCM13049P, Bifidobacterium longum NK219 having the accession number KCCM13050P, Lactococcus lactis NK209 having the accession number KCCM13048P, or any mixture thereof.” In view of the specification, KCCM13049P, KCCM13050P, and KCCM13048P are the biological deposit numbers associated with each of the bacterial strains (see pgs. 3-4, paras. [9]-[11]).
It is apparent that KCCM13049P, KCCM13050P, and KCCM13048P are required to practice the claimed invention because they are a necessary limitation for the success of the invention as stated in the claims. As a required element it must be known and readily available to the public or obtainable by a repeatable method set forth in the specification, or otherwise readily available to the public. If it is not so obtainable or available, the enablement requirements of 35 U.S.C. § 112, first paragraph, may be satisfied by a deposit of KCCM13049P, KCCM13050P, and KCCM13048P. See 37 CFR 1.802. One cannot practice the claimed invention without the recited strains having the recited deposit numbers. One cannot determine whether a bacterial strain has the necessary characteristics without access to KCCM13049P, KCCM13050P, and KCCM13048P. Therefore, access to KCCM13049P, KCCM13050P, and KCCM13048P is required to practice the invention. The specification does not provide a repeatable method for obtaining the bacterial strains of NK210, NK219 or NK209 without access to KCCM13049P, KCCM13050P, and KCCM13048P and they do not appear to be readily available material.
In the instant case, it appears the bacterial strains were deposited under the terms of the Budapest Treaty (see instant specification at pgs. 74-79).
If a deposit is made under the terms of the Budapest Treaty, then an affidavit or declaration by applicants or someone associated with the patent owner 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 someone associated with the patent owner 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 at an acceptable depository and that the following criteria have been met:
(a) during the pendency of this application, access to the invention will be afforded to one determined by the Commissioner to be entitled thereto;
(b) all restrictions imposed by the depositor on the availability to the public of the deposited material will be irrevocably removed upon granting of the patent;
(c) the deposit will be maintained for a term of at least thirty (30) years and at least five (5) years after the most recent request for the furnishing of a sample of the deposited material;
(d) a viability statement in accordance with the provisions of 37 CFR 1.807; and
(e) 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 CFR 1.809(d) should be added to the specification. See 37 CFR 1.803 - 37 CFR 1.809 for additional explanation of these requirements.
Claim Rejections - 35 USC § 112(a) – Scope of Enablement
Claims 34-38 and 40-43 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 a method of treating an inflammatory disease or cognitive dysfunction, does not reasonably provide enablement for a method of preventing any inflammatory disease or cognitive dysfunction in any subject. 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.
Enablement requires that the specification teach those in the art to make and use the invention without undue experimentation. Factors to be considered in determining whether a disclosure would require undue experimentation include (1) the nature of the invention, (2) the state of the prior art, (3) the predictability or lack thereof in the art, (4) the amount of direction or guidance present, (5) the presence or absence of working examples, (6) the quantity of experimentation necessary, (7) the relative skill of those in the art, and (8) the breadth of the claims.
The nature of the invention / Breadth of the claims
All questions of enablement are evaluated against the claimed subject matter. When considering whether claims in a utility patent application or patent are enabled, USPTO personnel will use the Wands factors to ascertain whether the amount of experimentation required to enable the full scope of the claimed invention is reasonable. See Guidelines for Assessing Enablement in Utility Applications and Patents in View of the Supreme Court Decision in Amgen Inc. et al. v. Sanofi et al., 89 FR 1563 (January 10, 2024). See also MPEP § 2164.01(a). The focus of the examination inquiry is whether everything within the scope of the claim is enabled. Accordingly, the first analytical step requires that the examiner determine exactly what subject matter is encompassed by the claims.
The broadest reasonable interpretation of independent claim 34 includes preventing any inflammatory disease or cognitive dysfunction in any subject by administering the claimed bacterial strains, NK210, NK219, and/or NK209. Prevention is typically defined within the art to include “the action of stopping something from happening or arising” (see Hodes et al., cited on Form 892 at pg. 2, col. 1, para. 3), and the instant specification does not provide any redefinition of the term. Hence, prevention would have to be experimentally demonstrated in the art by administering an effective dose of the proposed treatment prior to induction of the disease or condition in order to be prevented. In view of the dependent claims, an inflammatory disease may include, for example, obesity, sepsis, or burns (see claim 38), and a cognitive dysfunction may include, for example, Huntington’s disease (see claim 40). However, the remainder of the rejected claims have a broader scope and effectively encompass any inflammatory disease or cognitive dysfunction, while also including the conditions recited in claims 38 and 40, which are exemplified in the examiner’s discussion of the prior art below.
The amount of direction or guidance present
The specification states that the probiotics according to the present disclosure have high utility as a medicine or food and, in particular, can be used for preventing, treating, or relieving inflammatory diseases and cognitive dysfunction and for improving immune function, due to having “an excellent antioxidant effect, inflammation-relieving effect, nerve improving effect, cognition-improving effect, gut microbiota imbalance-improving effect, immune-regulating effect, etc.” (see pg. 33, para. [120]).
However, there is no specific guidance provided in the specification to differentiate methods to “treat” versus methods to “prevent”. Hence, the guidance provided for preventing any inflammatory disease or cognitive dysfunction in a subject is effectively the same as the guidance for treating these conditions.
The presence or absence of working examples
In Applicant’s Examples, the effect of administration in improving colitis was confirmed through changes in intestinal length, expression of inflammatory factors, and MPO activity. Specifically, the decrease in intestinal length was improved, MPO activity was decreased, and the expression of IFN-γ, TNF-α, and IL-10, which were suppressed by anticancer drugs, all increased. In particular, colitis was improved by increasing the expression of IL-10 compared to IFN-γ and IL-10 compared to TNF-α. See instant specification at page 57, para. [196].
Further, the administration of the strain according to the present disclosure showed excellent improvement effects in both the Y-maze task and the NOR task. In particular, this improvement effect showed a significant synergistic effect when the strains were used in combination. In addition, it was confirmed that there was an improvement on neuritis by improving the inflammatory indicators of the hippocampus, and in particular, lowering the levels of IFN-γ and TNF-α increased by endotoxin, increasing the expression of IL-10, and increasing the expression of IL-10 compared to IFN-γ and IL-10 compared to TNF-α. See instant specification at page 64, para. [214].
Finally, both Lactobacillus rhamnosus NK210 and Bifidobacterium longum NK219 were found to exhibit excellent antioxidant activity, anti-inflammatory efficacy, neurological enhancement, and inhibition in proliferation of intestinal Clostridium difficile and LPS production (see pg. 41, para. [145]). As shown in Table 2, the strains had a strong effect on BDNF and NPY expression (see pg. 41, Table 2) which are associated with stress, anxiety, depression, and cognitive impairment (see pg. 16, para. [16]).
Hence, Applicant’s Examples demonstrate that the administration of the bacterial strains improves inflammation by regulating the expression of pro-inflammatory cytokines (e.g., TNF-alpha) and increasing the relative expression of anti-inflammatory cytokines (e.g., IL-10) which may also be relevant to certain diseases/conditions related to cognitive dysfunction (e.g., neuro-inflammation). Further, the expression of neurological factors (e.g., BDNF and NPY) was shown to be improved, which may also be associated with cognitive dysfunction (discussed further in the next section). The examiner notes that these effects are further demonstrated by the disclosure through additional working examples that are not cited above. Therefore, it would be reasonable to conclude that the claimed method for “treating”, which includes management and alleviation of symptoms, has been demonstrated by the inventors.
The state of the prior art / The predictability or lack thereof in the art
In view of Walker, F. (Huntington's disease, The Lancet, Volume 369, Issue 9557,
2007, Pages 218-228), Huntington’s disease is an autosomal-dominant, progressive neurodegenerative disorder, and while the precise pathophysiological mechanisms of Huntington’s disease are poorly understood, research in transgenic animal models of the disorder is providing insight into causative factors and potential treatments (see Abstract). However, these treatments are limited to slowing the progression of the disease (see pg. 225, col. 1, para. 3), while the best therapeutic options for Huntington’s disease in the future could entail starting treatment in the asymptomatic phase of the disorder (see, pg. 225, col. 2, para. 1).
In view of Zuccato et al. (Role of brain-derived neurotrophic factor in Huntington's disease, Prog Neurobiol, 2007 Apr; 81(5-6): 294-330), BDNF is a small dimeric protein that is widely expressed in the adult mammalian brain and has been shown to promote the survival of all major neuronal types affected in Alzheimer’s disease (AD) and Parkinson’s disease (PD) (see Abstract). Zuccato teaches that the normal huntingtin protein, whose mutation causes Huntington’s Disease (HD), is involved in the physiological control of BDNF synthesis and transport in the brain, sustaining cortical BDNF gene transcription and driving BDNF vesicle sorting in neuronal cells, whereas both processes are simultaneously disrupted in HD. Zuccato discloses that it is possible that increasing endogenous BDNF production or supplying exogenous BDNF may have therapeutic effects if applied in an appropriate spatio-temporal context (see pg. 320, col. 2, para. 3).
Hence, there may be enough predictability in the art to for one to slow the progression or ameliorate the symptoms of a genetic disorder, such as Huntington’s disease, by the administration of therapeutics which increase endogenous BDNF. However, a person of skill would not reasonably expect that the administration of bacteria, even those shown to address certain effects of the disease, could prevent the disorder altogether, particularly in the case of an inherited genetic disorder, such as Huntington’s. In view of the prior art, treatment options for such disorders are limited, and the prior art is silent regarding actual prevention.
In view of the prior of Chen et al. (Inflammatory responses and inflammation-associated diseases in organs, Oncotarget, 2017 Dec 14; 9(6):7204-7218), various pathogenic factors, such as infection, tissue injury, or cardiac infarction, can induce inflammation by causing tissue damage (see pg. 7204, col. 1, para. 1). Chen teaches that inflammation is a common pathogenesis of many chronic diseases, including cardiovascular and bowel diseases, diabetes, arthritis, and cancer (see pg. 7204, col. 1, para. 2). Chen teaches that while inflammatory response processes depend on the precise nature of the initial stimulus and its location in the body, they all share a common mechanism: 1) cell surface pattern receptors recognize detrimental stimuli; 2) inflammatory pathways are activated; 3) inflammatory markers are released; and 4) inflammatory cells are recruited (see pg. 7205, col. 1, para. 1). Chen teaches that a better understanding of inflammatory response pathways and molecular mechanisms will undoubtedly contribute to improved prevention and treatment of inflammatory diseases (see pg. 7212, col. 2, para. 3).
Hence, while there may be some predictability in the art for controlling inflammation by the regulation of inflammatory cells (i.e., regulating the expression of inflammation-related cytokines), a person of skill would recognize that the detrimental stimuli which leads to inflammation at the onset of an inflammatory disease is not always predictable and cannot reasonably be prevented. This is clearly the case when addressing physical injuries, such as “burns”, which are explicitly within the scope of the claims (see claim 38).
The quantity of experimentation necessary / The relative skill of those in the art
Due to the lack of substantive evidence, data, and guidance in the instant disclosure and the prior art, one of ordinary skill in the art would have found it wholly unpredictable that the administration of the claimed bacterial strains could be used to entirely prevent any inflammatory disease (e.g., burns) or cognitive dysfunction (e.g., Huntington’s disease) from occurring within a subject. Consequentially, one of ordinary skill in the art would be subjected to an undue amount of experimentation to determine the feasibility of such a preventative method.
Conclusion
The amount of guidance, direction, and exemplification disclosed in the specification, as filed, would not have been sufficient to have enabled the skilled artisan to make and/or use the full scope of the claimed invention at the time the application was filed without undue and/or unreasonable experimentation. This is because the claims encompass methods for preventing medical conditions that a skilled artisan would not reasonably be expected to achieve based on the factors discussed above.
“Enabling the full scope of each claim is part of the quid pro quo of the patent bargain. A patentee who chooses broad claim language must make sure the broad claims are fully enabled. The scope of the claims must be less than or equal to the scope of the enablement to ensure that the public knowledge is enriched by the patent specification to a degree at least commensurate with the scope of the claims.” Sitrick v. Dreamworks, LLC, 516 F.3d 993, 999 (Fed. Cir. 2008).
In deciding In re Fisher, 166 USPQ 18, 24 (CCPA 1970), the Court indicated the more unpredictable an area is, the more specific enablement is necessary in order to satisfy the statute. “Tossing out the mere germ of an idea does not constitute enabling disclosure. While every aspect of a generic claim certainly need not have been carried out by an inventor, or exemplified in the specification, reasonable detail must be provided in order to enable members of the public to understand and carry out the invention.” Genentech Inc. v. Novo Nordisk A/S, 42 USPQ2d 1001, 1005 (CA FC 1997).
In conclusion, upon careful consideration of the factors used to determine whether undue experimentation is required, in accordance with the Federal Circuit decision of In re Wands, 858 F.2d at 737, 8 USPQ2d at 1404 (Fed. Cir. 1988), the amount of guidance, direction, and exemplification disclosed in the specification, as filed, is not deemed sufficient to have enabled the skilled artisan to make and/or use the full scope of the claimed invention at the time the application was filed without undue and/or unreasonable experimentation.
Claim Rejections - 35 USC § 102
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.
Claim(s) 34, 37 and 40 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Rogulja et al. (US 2020/0129572 A1, published 04/30/2020, cited on Form 892), hereafter, “Rogulja”.
Regarding claim 34, Rogulja teaches a method for treating damage induced by sleep deprivation (SD), the method comprising administering to an individual who is sleep deprived a probiotic that reduces reactive oxygen species (see pg. 21, para. [0191]); wherein the damage occurs in the brain (see para. [0192]); wherein the probiotic is Lactococcus lactis (see para. [0197]); and wherein the probiotic has a 16S rRNA sequence from Lactococcus lactis (see para. [0199]). Rogulja teaches that sleep deprivation may result in or increase the risk for depression, loss of memory, hallucinations, or psychosis (see pg. 5, para. [0101]). Hence, Rogulja teaches the method is for individuals who are at risk of cognitive dysfunction (i.e., depression) which meets the limitation of “preventing… cognitive dysfunction”. Rogulja teaches the probiotic comprises the strain, L. lactis subsp. lactis 111403 (see pg. 9, para. [0120]) which has a 16S rDNA sequence represented by SEQ ID NO: 1 (see pg. 11, para. [0130]).
As shown in the following alignment, Rogulja’s SEQ ID NO: 1 (bottom) comprises a sequence that is identical to the full-length of instant SEQ ID NO: 3 (top):
PNG
media_image1.png
856
644
media_image1.png
Greyscale
PNG
media_image2.png
574
644
media_image2.png
Greyscale
PNG
media_image3.png
283
646
media_image3.png
Greyscale
Although the L. lactis strain disclosed by Rogulja does not have the claimed accession number of KCCM13048P, it appears to be the same as the claimed Lactococcus lactis strain NK209. The instant specification states that the 16S rDNA sequence for identification of Lactococcus lactis NK209 is the same as instant SEQ ID NO: 3 (see pg. 6, para. [21]) and the L. lactis strain of Rogulja comprises the same 16S rDNA sequence, as shown above. It should be noted that a single strain can be deposited under different deposit numbers. Therefore, Rogulja anticipates the method of claim 34.
Regarding claim 37, Rogulja’s SEQ ID NO: 1 comprises a sequence that is identical to instant SEQ ID NO: 3, as discussed above.
Regarding claim 40, Rogulja teaches that sleep deprivation may result in or increase the risk for depression, loss of memory, hallucinations, or psychosis (see pg. 5, para. [0101]). Hence, Rogulja teaches the method is for individuals who are at risk of cognitive dysfunction, including depression, which meets the limitation of “preventing… cognitive dysfunction… wherein the cognitive dysfunction is… depression”.
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.
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.
Claim(s) 34, 37-39, 44 and 47-50 is/are rejected under 35 U.S.C. 103 as being unpatentable over Park et al. (US 2021/0138003 A1, published 05/13/2021, cited on Form 892), hereafter, “Park”, and further in view of GenBank CP033606.1 (cited on Form 892).
Regarding claim 34, Park teaches a method for preventing or treating inflammatory diseases by administering a Lactococcus lactis GEN3033 strain into the body (see pg. 6, para. [0099]). Park discloses that in order to isolate the GEN3033 strain, feces were provided from a normal 41 year old female (see pg. 9, para. [0153]). Park discloses that the nucleotide sequence of the rRNA for the obtained strain was analyzed and is represented by SEQ ID NO: 2, and the strain was deposited with the Korean Collection for Type cultures under accession number KCTC13684BP (see pg. 9, para. [0155]).
As shown in the following alignment, Park’s SEQ ID NO: 2 (bottom) comprises a 16S rDNA sequence that is identical to base pairs 1-1354 of instant SEQ ID NO: 3 (top):
PNG
media_image4.png
161
644
media_image4.png
Greyscale
PNG
media_image4.png
161
644
media_image4.png
Greyscale
PNG
media_image5.png
224
650
media_image5.png
Greyscale
PNG
media_image6.png
646
647
media_image6.png
Greyscale
Note that the sequence disclosed by Park ends at the position corresponding to base pair 1354 of instant SEQ ID NO: 3. Therefore, Park does not disclose a sequence comprising the last 7 base pairs of instant SEQ ID NO: 3 (bp 1355-1361).
GenBank CP033606.1 is identified as the complete genome of Lactococcus lactis strain IL6288 (see Title), which comprises a sequence that is identical to Park’s SEQ ID NO: 2. Therefore, a person of skill could have selected this strain, which was known in the prior art at the time of filing, based on Park’s disclosure of SEQ ID NO: 2. As shown in the following alignment, GenBank CP033606.1 comprises a sequence (bottom) that is identical to instant SEQ ID NO: 3 (top):
PNG
media_image7.png
708
645
media_image7.png
Greyscale
PNG
media_image8.png
507
645
media_image8.png
Greyscale
PNG
media_image9.png
58
650
media_image9.png
Greyscale
PNG
media_image9.png
58
650
media_image9.png
Greyscale
It would have been obvious at the time of filing for a person of ordinary skill in the art to have arrived at the claimed invention by selecting the strain disclosed by GenBank for use in the method taught by Park, because the GenBank strain is disclosed to have the same 16S rRNA sequence disclosed by Park. One would have been motivated to do so, because Park teaches strains having this identity are useful for preventing or treating inflammatory diseases. One would have recognized that both prior art strains share a key, conserved structural element (16S rDNA) commonly used in the art to determine the identity of a bacterial strain. It should also be noted that a single strain can be deposited under different deposit numbers. Because the GenBank strain was known in the art at the time of filing and possesses the same structural characteristic disclosed by Park, a person of skill would have recognized this strain could be used in the methods of Park’s disclosure. Therefore, one could have substituted the strain taught by Park with the strain disclosed by GenBank, while recognizing the results of the substitution to be predictable, and there would have been a reasonable expectation for success. Hence, the combination would have been readily apparent and deemed to be a mere (B) simple substitution of one known element for another to obtain predictable results (see MPEP 2143(I): Rationales to support rejections under 35 U.S.C. 103).
Regarding claim 37, GenBank CP033606.1 discloses Lactococcus lactis strain IL6288 which comprises a sequence that is identical to instant SEQ ID NO: 3, as discussed above.
Regarding claim 38, Park teaches that the inflammatory disease may be gout or arthritis (see pg. 2, para. [0026]).
Regarding claim 39, Park teaches that the inflammatory disease may be ulcerative colitis or Crohn’s disease (see pg. 2, para. [0026]).
Regarding claim 44, Park teaches a method for preventing or treating cancers and immune diseases by administering a Lactococcus lactis GEN3033 strain into the body (see pg. 6, para. [0099]). Park teaches the GEN3033 strain may exhibit an anticancer effect and an immune enhancing effect by increasing the production IFN-gamma (see pg. 4, para. [0044]). Hence, it would have been obvious to have administered an effective amount of the Lactococcus lactis strain to improve immune function.
Regarding claim 47, GenBank CP033606.1 discloses Lactococcus lactis strain IL6288 which comprises a sequence that is identical to instant SEQ ID NO: 3, as discussed above. Hence, the claim is obvious for the same reasons discussed regarding claims 34 and 44.
Regarding claim 48, Park teaches a method for preventing or treating cancers in a subject in need thereof, comprising administering an effective amount of a Lactococcus lactis GEN3033 strain in combination with an anticancer chemotherapeutic agent (see pg. 4, para. [0047]). Park teaches that anticancer chemotherapeutic agents have the effect of killing cancer cells, but they also affect normal cells which leads to side effects such as immunity decline (see pg. 1, para. [0011]). Park teaches the Lactococcus lactis strain may be utilized as an excellent anticancer agent by simultaneously exhibiting the effect of inhibiting the proliferation of cancer cells and having an immune enhancing effect when administered in combination with a chemotherapeutic agent (see pg. 6, para. [0097]). Hence, it would have been obvious to have administered the strain to a subject recovering from an occurrence of immunodeficiency (immunity decline) due to anticancer drug treatment.
Regarding claim 49, Park teaches the Lactococcus lactis GEN3033 strain enhances immune activity (see pg. 1, para. [0005]). Park discloses that the Lactococcus lactis strain remarkably increases the activity of memory T cells, resulting in an excellent immune activity (see pg. 10, para. [0165]). Furthermore, the further limitation of the claim does not affect the structure or steps of the claimed invention, and the improved immune function is presumed to be an inherent property of administering the Lactococcus lactis strain. See MPEP 2112.
Regarding claim 50, Park teaches GEN3033 enhances immune activity (see pg. 1, para. [0005]) and teaches a method for preventing immune diseases by administering a Lactococcus lactis GEN3033 strain into the body (see pg. 6 [0099]). Hence, it would have been obvious to have administered the Lactococcus lactis strain for the enhancement of immunity in a subject having normal immunity, because Park teaches that doing so may prevent immune disease.
Conclusion
No claims are allowed.
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Cook et al. (US 2023/0068960 A1, effectively filed 09/24/2019) teach a method for treating or preventing a disease, disorder, or condition associated with one or more of dysbiosis of the intestinal microbiome, inflammation, infection, allergy, or immune dysfunction in a subject in need thereof, the method comprising administering to the subject (i) a prebiotic mixture comprising one or more human milk oligosaccharides and (ii) at least one probiotic strain of bacterium comprising B. longum subsp. longum (see claim 1), wherein the disease, disorder, or condition comprises one or more of obesity, type II diabetes, a chronic inflammatory disease, an autoimmune disease (see claim 9), or inflammatory bowel disease (see claim 10). In certain embodiments, the at least one probiotic strain may be L. rhamnosus, Bifidobacterium longum subsp. longum, and Lactococcus lactis (see pg. 19, para. [0176]). Cook discloses exemplary full or partial 16S sequences for L. rhamnosus (SEQ ID NO: 33), B. longum subsp. longum (SEQ ID NO: 14), and L. lactis (SEQ ID NO: 43).
However, the 16S sequences taught by Cook are not identical to instant SEQ ID NOs 1, 2, and 3 of the present disclosure. As these sequences are disclosed in the instant specification as being structural characteristics of the bacterial strains deposited under KCCM13049P, KCCM13050P, and KCCM13048P, respectively, the claimed invention cannot be anticipated by Cook. Further, SEQ ID NO: 1 (KCCM13049P) and SEQ ID NO: 2 (KCCM13050P) are free of the prior art of record, so it would not have been obvious to have substituted an equivalent strain, because no strain having either of these sequences has been found in the prior art of record. Furthermore, even if these strains were the same, the focus of Cook’s disclosure is most relevant to methods using B. infantis and B. longum (see Abstract; claim 1) and only the B. infantis strain is present in Cook’s working examples. Conversely, the embodiments of Cook that include the L. rhamnosus strain (relevant to KCCM13049P) or the L. lactis strain (relevant to KCCM13048P), and any potential embodiment encompassing a combination of these strains, would require one to select these species from a genus of at least 50 specific bacterial strains (see Cook at pg. 19, Table 1), or from a list of bacteria broadly disclosed at the genus and species level (see pg. 18, para. [0176] to pg. 19, para. [0177]).
Thus, in the absence of evidence to the contrary, which is the initial burden of the examiner to establish, the methods of claims 35-36, 41-43, 45-46 and 51-53, which comprise administering the strains deposited under accession numbers KCCM13049P and/or KCCM13050P, are free of the prior art of record and are nonobvious in view of the closest prior art.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to DENNIS ARMATO whose telephone number is (703)756-5348. The examiner can normally be reached Mon-Fri 11:00am-7:30pm EST.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Melenie Gordon can be reached at (571) 272-8037. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/DENNIS IGNATIUS ARMATO JR/Examiner, Art Unit 1651
/MELENIE L GORDON/Supervisory Patent Examiner, Art Unit 1651