Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 18 May 2026 has been entered.
DETAILED ACTION
Claims 18 and 31 are amended. Claims 19-20 are canceled.
Claims 18 and 25-31 are pending and under examination.
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.
(Maintained) Claims 18 and 28 are rejected under 35 U.S.C. 103 as being unpatentable over Cutcliffe et al. (US 20200268811 A1, 27 August 2020) in view of Strandwitz et al. (US 20190070225 A1, published 07 March 2019).
Cutcliffe teaches a method of treating an ocular disorder, including macular degeneration and glaucoma, comprising orally administering a therapeutic composition comprising microorganisms that increase butyrate in the subject (Cutcliffe [0246] and claims 55 and 68). Lactobacillus plantarum is taught to be one organism suitable for use in the method (Cutcliffe [0037] and [0347]).
Cutcliffe does not teach their Lactobacillus plantarum in their composition is strain NK151 having the accession number KCCM12783P.
Strandwitz teaches administering a therapeutic composition comprising a Lactobacillus plantarum strain with a 16s rDNA having at least 97% identity to a SEQ ID NO: 152 (Strandwitz pg. 9 Table 2, claims 1, 5, and 24, and SEQ ID NO: 152).
Strandwitz does not teach the Lactobacillus plantarum strain NK151 having the accession number KCCM12783P.
However, the 16s rDNA sequence of instant SEQ ID NO: 1 of Lactobacillus plantarum strain NK151 having the accession number KCCM12783P as recited in instant claim 18 is 100% identical to Strandwitz’s 16s rDNA sequence SEQ ID NO: 152 Lactobacillus plantarum strain (See sequence search results in IFW for alignment).
Therefore, it would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date of the present invention to add Strandwitz’s Lactobacillus plantarum strain in Cutcliffe’s method of treating ocular diseases macular degeneration and glaucoma comprising administering Lactobacillus plantarum strains.
One of ordinary skill in the art would have been motivated to do so with a reasonable expectation of success because Cutcliffe taught that the ocular diseases macular degeneration and glaucoma can be treated by administering therapeutic compositions comprising Lactobacillus plantarum strains, and Strandwitz teaches one such Lactobacillus plantarum strain in a composition which can be administered to a subject. Thus, one of ordinary skill in the art would reasonably expect that Strandwitz’s composition comprising a Lactobacillus plantarum strain with a 16s rDNA sequence 100% identical to the instant strain Lactobacillus plantarum strain NK151 having the accession number KCCM12783P would be suitable for use in Cutcliffe’s method of treating ocular diseases.
As mentioned above, since the Lactobacillus plantarum strain NK151 having the accession number KCCM12783P of the instant invention comprises a 16s rDNA sequence that is 100% identical to the 16s rDNA sequence of the Lactobacillus plantarum strain taught by Strandwitz, it would have been prima facie obvious to one of ordinary skill in the art to use the instant strain, or any strain of Lactobacillus plantarum that has a 16s rDNA sequence at least 97% identical to Strandwitz’s SEQ ID NO: 152, in the obvious method of Cutcliffe in view of Strandwitz.
(Maintained) Claims 25-27 and 29-31 are rejected under 35 U.S.C. 103 as being unpatentable over Cutcliffe in view of Strandwitz as applied to claims 18 and 28 above, and further in view of Nandakumar et al. (WO 2019036510 A1, published 21 February 2019), and Odamaki et al. (US 20210139842 A1, published 13 May 2021, effectively filed 08 December 2017).
Regarding claims 25-27, Cutcliffe teaches a method of treating an ocular disorder, including macular degeneration and glaucoma, comprising orally administering a therapeutic composition comprising microorganisms that increase butyrate in the subject (Cutcliffe [0246] and claims 55 and 68). The therapeutic composition comprises Lactobacillus plantarum, Bifidobacterium bifidum, and Bifidobacterium longum (Cutcliffe [0037], [0319], [0321], and [0347]).
Cutcliffe and Strandwitz do not teach Bifidobacterium bifidum NK175 having the accession number KCCM12784P or Bifidobacterium longum NK173 having the accession number KCCM13046P.
Nandakumar teaches SEQ ID NO: 80 and multiple Bifidobacterium bifidum strains having a 16s rDNA sequence that is at least 95% identical to SEQ ID NO: 80 (Nandakumar pg. 3 para. 7 and Fig. 16). The Bifidobacterium bifidum NK175 having the accession number KCCM12784P of the present invention has a 16s rDNA sequence SEQ ID NO: 2, which is 99.5% identical to Nandakumar’s SEQ ID NO: 80 (see Sequence Search results in IFW for alignment). Thus, the Bifidobacterium bifidum NK175 having the accession number KCCM12784P of the present invention encompasses Nandakumar’s Bifidobacterium bifidum strains having 16s rDNA sequences at least 95% identical to Nandakumar’s SEQ ID NO: 80. Additionally, Nandakumar teaches administration of compositions comprising their Bifidobacterium bifidum strains (Nandakumar pg. 3 paras. 8-9).
However, Cutcliffe, Strandwitz, and Nandakumar do not teach Bifidobacterium longum NK173 having the accession number KCCM13046P.
Odamaki teaches SEQ ID NO: 1 and compositions comprising Bifidobacterium longum strain NITE BP-02568 that has a 16s rDNA sequence 100% identical to Odamaki’s SEQ ID NO:1 (Odamaki [0065], [0067], [0230], and Table 2). The Bifidobacterium longum NK173 having the accession number KCCM13046P of the present invention has a 16s rDNA sequence SEQ ID NO: 3, which is 100% identical to Odamaki’s SEQ ID NO: 1 (see Sequence Search results in IFW for alignment). Thus, the Bifidobacterium longum NK173 having the accession number KCCM13046P of the present invention encompasses Odamaki’s Bifidobacterium longum strain NITE BP-02568. Additionally, Odamaki teaches administering a composition comprising Bifidobacterium longum strain NITE BP-02568 (Odamaki [0038]-[0039] and [0122]).
It would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date of the present invention to combine 1) a Lactobacillus plantarum strain having a 16s rDNA sequence at least 97% identical to Strandwitz’s SEQ ID NO: 152, including the instant strain Lactobacillus plantarum strain NK151 having the accession number KCCM12783P; 2) a Bifidobacterium bifidum strain having a 16s rDNA sequence that is at least 95% identical to Nandakumar’s SEQ ID NO: 80, including the instant strain Bifidobacterium bifidum NK175 having the accession number KCCM12784P; and 3) a Bifidobacterium longum strain having a 16s rDNA sequence 100% identical to Odamaki’s SEQ ID NO: 1, including the instant strain Bifidobacterium longum NK173 having the accession number KCCM13046P, into a composition to be administered in Cutcliffe’s method of treating an ocular disease comprising administering a therapeutic composition comprising Lactobacillus plantarum, Bifidobacterium bifidum, and Bifidobacterium longum. One of ordinary skill in the art would have been motivated to do so with a reasonable expectation of success because Cutcliffe’s teaches administering a therapeutic composition comprising Lactobacillus plantarum, Bifidobacterium bifidum, and Bifidobacterium longum to treat ocular diseases. Strandwitz, Nandakumar, and Odamaki teach strains of Lactobacillus plantarum, Bifidobacterium bifidum, and Bifidobacterium longum, respectively, in administered compositions. Thus, one of ordinary skill in the art would reasonably expect that Strandwitz’s composition comprising a Lactobacillus plantarum strain with a 16s rDNA sequence 100% identical to the instant strain Lactobacillus plantarum strain NK151 having the accession number KCCM12783P; Nandakumar’s composition comprising a Bifidobacterium bifidum strain with a 16s rDNA sequence 100% identical to the instant strain Bifidobacterium bifidum strain NK175 having the accession number KCCM12784P; and Odamaki’s composition comprising a Bifidobacterium longum strain with a 16s rDNA sequence 100% identical to the instant strain Bifidobacterium longum strain NK173 having the accession number KCCM13046P would be suitable for use in Cutcliffe’s method of treating ocular diseases.
Regarding claims 29-31, Cutcliffe teaches that the concentrations of Lactobacillus plantarum, Bifidobacterium bifidum, and/or Bifidobacterium longum in their pharmaceutical composition may range from 101 to 1018 CFUs (Cutcliffe [0446]).
Strandwitz teaches their composition may comprise 104-1011 CFU or greater of the bacterial species (Strandwitz [0120]), but does not teach any concentrations of Bifidobacterium bifidum or Bifidobacterium longum.
Nandakumar teaches the designed composition used within their disclosed examples comprised 107 CFU/strain (Nandakumar pgs. 33-34 bridging para.), but does not teach any concentration of Lactobacillus plantarum or Bifidobacterium longum.
Odamaki teaches that administered composition may comprise the strain in concentrations ranging from 106 to 1012 CFUs (Odamaki [0137]), but does not teach any concentration of Lactobacillus plantarum or Bifidobacterium bifidum.
However, none of Cutcliffe, Strandwitz, Nandakumar, or Odamaki teach any ratios of each of their strains to each other based on colony forming units.
MPEP §2144.05(II)(A) states “[g]enerally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955)”.
MPEP §2144.05(II)(B) states “[i]n order to properly support a rejection on the basis that an invention is the result of "routine optimization", the examiner must make findings of relevant facts, and present the underpinning reasoning in sufficient detail. The articulated rationale must include an explanation of why it would have been routine optimization to arrive at the claimed invention and why a person of ordinary skill in the art would have had a reasonable expectation of success to formulate the claimed range. See In re Stepan, 868 F.3d 1342, 1346, 123 USPQ2d 1838, 1841 (Fed. Cir. 2017).
In the instant case, one of ordinary skill in the art would have performed routine experimentation to optimize the relative concentrations and ratios of each of the Lactobacillus plantarum, Bifidobacterium bifidum, and Bifidobacterium longum strains taught by Cutcliffe, Strandwitz, Nandakumar, and Odamaki in order to maximize the therapeutic ability of each strain in the obvious combined composition. One of ordinary skill in the art would have had a reasonable expectation of success in optimizing the concentrations because each of the Lactobacillus plantarum, Bifidobacterium bifidum, and Bifidobacterium longum strains were taught to have suitable therapeutic CFU concentrations within their compositions. Thus, one of ordinary skill in the art would have started at those disclosed CFU concentrations for each strain and optimized the relative amounts of each strain to maximize the therapeutic ability of each strain in the obvious combined composition.
Response to Arguments
Applicant's arguments filed 18 May 2026 and the Declaration by Dr. Dong Hyun Kim filed 08 June 2026 (hereinafter “Kim Declaration”) have been fully considered but they are not persuasive.
Regarding Applicant’s arguments that reference Cutcliffe is not directed towards ocular treatment, and Cutcliffe only mentions ocular diseases in a single passage without working examples or animal model data (Remarks pg. 5 last para. and pg. 6 para. 1), Cutcliffe teaches a method of treating macular degeneration and glaucoma, both of which are ocular diseases/disorders comprising orally administering a therapeutic composition comprising Lactobacillus plantarum bacteria that increase butyrate in the subject (Cutcliffe [0246] and claims 55 and 68, [0037] and [0347]). Although Cutcliffe does not provide animal model data showing direct treatment of ocular disease, Cutcliffe does teach that alterations of the gut microbiota can be implicated in the pathophysiology of a disorder, including neurological disorders such as ocular diseases, macular degeneration and glaucoma (Cutcliffe [244]-[245]). one of ordinary skill in the art would take into consideration Cutcliffe’s teachings and conclude that they could treat macular degeneration and glaucoma, both of which are ocular diseases/disorders, by orally administering a therapeutic composition comprising Lactobacillus plantarum bacteria that increase butyrate in the subject, as taught by Cutcliffe, especially in absence of any contradictory evidence that would call into question Cutcliffe’s teachings.
Regarding Applicant’s arguments that Cutcliffe does not provide a motivation to select Lactobacillus plantarum for ocular treatment (Remarks pg. pg. 6 last para. through pg. 7 para. 2), the microorganisms that Cutcliffe teaches are suitable for treating the ocular diseases are all found in Cutcliffe’s Markush group of alternative microorganisms, and that group comprises Lactobacillus plantarum (Cutcliffe [37] and [347]). Thus, one of ordinary skill in the art would have understood that Lactobacillus plantarum would be useful to perform Cutcliffe’s method. The size of the Markush group itself is not sufficient to overcome a prima facie case of obviousness because Cutcliffe does teach Lactobacillus plantarum to be useful in their method. Cutcliffe may have identified many other microorganisms that are also capable of affecting Cutcliffe’s treatment, but Cutcliffe’s identification of these other microorganisms does not negate their conclusion that Lactobacillus plantarum is suitable in the method.
Regarding Applicant’s arguments that Strandwitz does not address ocular treatment (Remarks pg. 8 para. 1), Cutcliffe teaches ocular disease treatment comprising administering Lactobacillus plantarum, and Strandwitz teaches one strain of Lactobacillus plantarum in an administrable composition.
Regarding Applicant’s arguments that identity to 16s rDNA sequence is not sufficient to establish that two Lactobacillus plantarum strains are the same strain or are interchangeable for therapeutic purposes (Remarks pg. 8 paras. 2-3), Strandwitz’s Lactobacillus plantarum that comprises a 16s rDNA sequence that is 100% identical to instant SEQ ID NO: 1 attributed to Lactobacillus plantarum NK151 accession number KCCM12783P fills all of the claimed structural requirements for the Lactobacillus plantarum used in the instant method. It is a bacteria of the species Lactobacillus plantarum and it comprises the claimed 16s rDNA sequence. Although Strandwitz does not label their Lactobacillus plantarum strain as Lactobacillus plantarum NK151 accession number KCCM12783P, all of the structural requirements of the claimed Lactobacillus plantarum are met. There is also no evidence presented that demonstrates that one of ordinary skill in the art would conclude Strandwitz’s Lactobacillus plantarum strain comprising a 16s rDNA sequence that is 100% identical to instant SEQ ID NO: 1 differs from claimed Lactobacillus plantarum NK151 accession number KCCM12783P. The preponderance of evidence as currently presented indicates to one of ordinary skill in the art that Strandwitz’s Lactobacillus plantarum and the instant Lactobacillus plantarum NK151 accession number KCCM12783P appear to be the same or functional indistinct organisms, thus are obvious over one another.
Regarding Applicant’s arguments that strain NK151 has a whole-genome distinctiveness, referring to varying levels of OrthoANI values when compared to a variety of other Lactobacillus plantarum strains (Remarks pg. 9 para. 2 through pg. 10, and Kim Declaration pg. 2), there is no comparison between Applicant’s NK151 strain and Strandwitz’s Lactobacillus plantarum strain, thus there is no evidence that this whole-genome distinctiveness is also applicable to Strandwitz’s disclosure and the rejection at hand.
Regarding Applicant’s arguments that Lactobacillus plantarum NK151 had unexpected superior effects on anti-inflammatory activity and treating ocular diseases as compared to multiple other Lactobacillus plantarum strains (Remarks pg. 11 through pg. 12 para. 1, and Kim Declaration pg. 3 through pg. 4 para. 1), the instant Lactobacillus plantarum NK151 strain was not compared to Strandwitz’s Lactobacillus plantarum strain which Applicant argues is not the same as or is functionally distinct from the claimed NK151 strain. The prima facie case of obviousness presents Strandwitz’s Lactobacillus plantarum strain with a 16s rDNA sequence 100% identical to the instant strain Lactobacillus plantarum strain NK151 having the accession number KCCM12783P would be suitable for use in Cutcliffe’s method of treating ocular diseases. Applicant’s presented evidence of unexpected results as compared to other Lactobacillus plantarum strains does show some distinctiveness of strain NK151 as compared to those strains, but it does not provide evidence that Strandwitz’s Lactobacillus plantarum strain would behave differently, or would not be able to produce these same superior results. In other words, Applicant still has not shown that Strandwitz’s Lactobacillus plantarum and the instant Lactobacillus plantarum strain NK151 are different strains that would produce different therapeutic results such that the instant Lactobacillus plantarum strain NK151 would be considered to have unexpected superior results when compared to Strandwitz’s Lactobacillus plantarum strain.
Regarding Applicant’s arguments that Lactobacillus plantarum NK151 had unexpected superior effects on treating ocular diseases, referring to Examples 2-3 and 6 (Remarks pg. 12 last para. through pg. 14, and Kim Declaration pg. 4 paras. 2-4), it is noted that Example 6 only compares the effectiveness of the 3 claimed strains relative to each other. There is no data comparing the effectiveness of Lactobacillus plantarum NK151 to other Lactobacillus plantarum strains known in the art, especially Strandwitz’s Lactobacillus plantarum strain. Regarding Example 2-3, Applicant’s assertion that Lactobacillus plantarum NK151 exhibits superior anti-inflammatory and growth-inhibitory activity relative to the other Lactobacillus plantarum strains (referring to specification pg. 28 Table 3) is not convincing to establish that Lactobacillus plantarum NK151 has unexpectedly superior effects on treating ocular diseases. Firstly, the claims are not limited to anti-inflammation or growth inhibition. Additionally, only one other Lactobacillus plantarum strain (NK152) was evaluated in Example 2-3, and that strain was a product of Applicant’s isolation process shown in Example 1 (specification pgs. 25-26), not a Lactobacillus plantarum strain known in the art to be suitable for treating ocular diseases. Thus, there is no data demonstrating any superior effects of Lactobacillus plantarum NK151 treating ocular diseases.
Regarding Applicant’s arguments that the CFU-based ratios recited in claims 29-31 would not have been obvious to optimize because one of ordinary skill in the art would have had to selected the three microorganisms as claimed for use in the method, and the CFU ratio of Cutcliffe spans from 101 to 1018 which spans 17 orders of magnitude, which would provide no meaningful guidance on relative CFU ratios between the strains (Remarks pg. 16 paras. 2-4), as described in the rejections above, one of ordinary skill in the art would have selected the three microorganisms as claimed. Additionally, just because Cutcliffe provides a broad range of CFU concentrations for their composition does not mean that one of ordinary skill in the art would have found it impossible to optimize the relative CFU concentrations of each of the components in the obvious composition. One of ordinary skill in the art would take into consideration a result effective variable that is relevant to the obvious method, namely the therapeutic ability/efficiency of each strain in the obvious combined composition. One of ordinary skill in the art would have had a reasonable expectation of success in optimizing the concentrations because each of the Lactobacillus plantarum, Bifidobacterium bifidum, and Bifidobacterium longum strains were taught to have suitable therapeutic CFU concentrations within their compositions. Thus, one of ordinary skill in the art would have started at those disclosed CFU concentrations for each strain and optimized the relative amounts of each strain to maximize the therapeutic ability of each strain in the obvious combined composition.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Alexander M Duryee whose telephone number is (571)272-9377. The examiner can normally be reached Monday - Friday 9:00 am - 5:00 pm.
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/Alexander M Duryee/Examiner, Art Unit 1657
/LOUISE W HUMPHREY/Supervisory Patent Examiner, Art Unit 1657
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