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 .
Withdrawal of Rejections
The response and amendments filed on 10/01/2025 are acknowledged. Any previously applied minor objections and/or minor rejections (i.e., formal matters), not explicitly restated here for brevity, have been withdrawn necessitated by Applicant’s formality corrections and/or amendments. For the purposes of clarity of the record, the reasons for the Examiner’s withdrawal, and/or maintaining, if applicable, of the substantive or essential claim rejections are detailed directly below and/or in the Examiner’s Response to Arguments section.
Briefly, the previous 35 U.S.C. 112(b) rejections have been withdrawn necessitated by Applicant’s amendments. The previous 35 U.S.C 112(a) rejection for the biological deposits has been withdrawn necessitated by Applicant’s submission of a Biological Deposit statement providing assurances. The previous 35 U.S.C. 103 rejections have been withdrawn necessitated by amendments; however, new grounds of rejection are set forth below.
The following rejection and/or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application.
New Grounds of Rejection Necessitated by Amendments
Claim Rejections - 35 USC § 103, Obviousness
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claims 1, 3, 8-9, and 12-14 are rejected under 35 U.S.C. 103 as being unpatentable over Schneider (WO 2017/218680; Date of Publication: December 21, 2017 – previously cited) in view of Kawaguchi (WO 2020/075637; Date of Publication: April 16, 2020 – previously cited).
Schneider’s general disclosure relates to compositions of purified bacterial strains for the treatment of pathogenic infections, such as Clostridium difficile infections (see, e.g., Schneider, “Field of Invention”, pg. 1, lines 9-11).
Regarding claims 1 and 9 pertaining to the composition, Schneider teaches a composition comprising cells of Clostridium scindens and Blautia producta for treatment or prevention of C. difficile infections (see, e.g., Schneider, “Summary of Invention”, pg. 3, lines 7-8, 11, 14). Moreover, Schneider teaches that the composition can be a pharmaceutical composition (see, e.g., Schneider, pg. 18, line 5), or a food composition (see, e.g., Schneider, pg. 18, lines 7-9). Additionally, Schneider teaches that the bacterial cells can be lyophilized (see, e.g., Schneider, pg. 16, lines 23-24). The preamble recitation of “for preventing or treating Clostridium difficile infection” is intended use and does not impart a structural limitation (see, e.g., MPEP 2111.02(II)). Therefore, based on the BRI of independent claims 1 and 9 and for the purposes of applying prior art, the instant invention relates to a composition comprising Clostridium scindens, Blautia producta, and Enterococcus faecium.
Regarding claim 3 pertaining to Clostridium scindens KBL987 strain, it cannot be ascertained if the prior art strain of Schneider and the instant claimed strain Clostridium scindens KBL987 are the same. However, it is the Examiner’s position that they are substantially similar since they share similar properties/function:
Claimed Clostridium scindens KBL987 strain
Genus, Species: Clostridium scindens
Growth: Anaerobic fermentation techniques (see, e.g., instant Spec, pg. 10)
Intended use: Clostridium difficile growth inhibition (see, e.g., instant Spec, pg. 2)
Dosage forms: Oral, rectal, or intravenous delivery (see, e.g., instant Spec, pg. 11)
Treatment results: Inhibits the growth and/or survival of C. difficile (see, e.g., instant Spec, pg. 29)
Prior Art Strain (Schneider’s Clostridium scindens)
Genus, Species: Clostridium scindens
Growth: Anaerobic fermentation techniques (see, e.g., Schneider, pg. 95, lines 31-34)
Intended use: Clostridium difficile growth inhibition (see, e.g., Schneider, pg. 25, lines 14-18)
Dosage forms: Oral or rectal delivery (see, e.g., Schneider, pg. 18, lines 32-34)
Treatment results: Inhibits the growth and/or survival of C. difficile (see, e.g., Schneider, pg. 25, lines 22-23)
Therefore, the cited reference discloses Clostridium scindens (see, e.g., Schneider, “Summary of Invention”, pg. 3, lines 7-8, 11, 14) which appears to be identical to the presently claimed strain since it is suitable for inhibiting Clostridium difficile growth and is the same bacterial species as the claimed microorganism. Furthermore, it appears that the Clostridium scindens strain, such as taught by Schneider, is structurally the same to that as instantly claimed; therefore, it would also perform the intended use of treating/preventing Clostridium difficile infection.
Regarding claim 3 pertaining to Blautia producta KBL988, Blautia producta KBL990, and Blautia producta KBL991, it cannot be ascertained if the prior art strain of Schneider and the instantly claimed Blautia producta KBL988, Blautia producta KBL990, and Blautia producta KBL991 strains are the same. However, it is the Examiner’s position that they are substantially similar since they share similar properties/functions:
Claimed Blautia producta KBL988, Blautia producta KBL990, and
Blautia producta KBL991 strains
Genus, Species: Blautia producta
Growth: Anaerobic fermentation techniques (see, e.g., instant Spec, pg. 10)
Intended use: Clostridium difficile growth inhibition (see, e.g., instant Spec, pg. 2)
Dosage forms: Oral, rectal, or intravenous delivery (see, e.g., instant Spec, pg. 11)
Treatment results: Inhibits the growth and/or survival of C. difficile (see, e.g., instant Spec, pg. 29)
Prior Art Strain (Schneider’s Blautia producta)
Genus, Species: Blautia producta
Growth: Anaerobic fermentation techniques (see, e.g., Schneider, pg. 95, lines 31-34)
Intended use: Clostridium difficile growth inhibition (see, e.g., Schneider, pg. 25, lines 14-18)
Dosage forms: Oral or rectal delivery (see, e.g., Schneider, pg. 18, lines 32-34)
Treatment results: Inhibits the growth and/or survival of C. difficile (see, e.g., Schneider, pg. 25, lines 22-23)
Therefore, the cited reference discloses Blautia producta (see, e.g., Schneider, “Summary of Invention”, pg. 3, lines 7-8, 11, 14) which appears to be identical to the presently claimed strain since it is suitable for inhibiting Clostridium difficile growth and is the same bacterial species as claimed microorganisms. Furthermore, it appears that the Blautia producta strain, such as taught by Schneider, is structurally the same to the instantly claimed Blautia producta strains; therefore, it would also perform the intended use of treating/preventing Clostridium difficile infection.
Regarding claims 8 and 12 pertaining to the concentration, Schneider teaches that the composition can contain about 108 CFU of bacteria per dosage amount (see, e.g., Schneider, pg. 100, lines 13-16). The skilled artisan would readily understand that the dosage amount can be 1 mL.
Regarding claims 13-14 pertaining to administering the pharmaceutical composition, Schneider teaches administration of a bacterial composition comprising Clostridium scindens and Blautia producta for treatment or prevention of C. difficile infections (see, e.g., Schneider, “Summary of Invention”, pg. 3, lines 7-8, 11, 14 & pg. 18, lines 9-11). Moreover, Schneider teaches that the composition can be a pharmaceutical composition (see, e.g., Schneider, pg. 18, line 5), or a food composition (see, e.g., Schneider, pg. 18, lines 7-9). Additionally, Schneider teaches that the bacterial cells can be lyophilized (see, e.g., Schneider, pg. 16, lines 23-24). Furthermore, Schneider teaches that the composition can comprise Blautia faecis (see, e.g., Schneider, pg. 3, lines 25-26).
However, Schneider does not teach: wherein the composition comprises Enterococcus faecium (claims 1 and 13); or wherein the Enterococcus faecium is Enterococcus faecium KBL986 strain (claim 3).
Kawaguchi’s general disclosure relates to bacteria belonging to the genus Enterococcus for the treatment or prevention of Clostridium difficile infections (see, e.g., Kawaguchi, English Translation, abstract).
Regarding claims 1 and 13 pertaining to Enterococcus faecium, Kawaguchi teaches a prophylactic and/or therapeutic treatment for Clostridium difficile infection comprising a bacterium belonging to the genus Enterococcus, wherein the bacterium can be Enterococcus faecium (see, e.g., Kawaguchi, English Translation, Industrial Applicability, pg. 3).
Regarding claim 3 pertaining to is Enterococcus faecium KBL986, it cannot be ascertained if the prior art strain of Kawaguchi and the instant claimed strain Enterococcus faecium KBL986 are the same. However, it is the Examiner’s position that they are substantially similar since they share similar properties/function:
Claimed Enterococcus faecium KBL986 strain
Genus, Species: Enterococcus faecium
Growth: Anaerobic fermentation techniques (see, e.g., instant Spec, pg. 10)
Intended use: Clostridium difficile growth inhibition (see, e.g., instant Spec, pg. 2)
Dosage forms: Oral, rectal, or intravenous delivery (see, e.g., instant Spec, pg. 11)
Treatment results: Inhibits the growth and/or survival of C. difficile (see, e.g., instant Spec, pg. 29)
Prior Art Strain (Kawaguchi’s Enterococcus faecium)
Genus, Species: Enterococcus faecium
Growth: Anaerobic (see, e.g., Kawaguchi, English Translation, “Description”, pgs. 2-4)
Intended use: Prophylactic and/or therapeutic agent for treatment of C. difficile infection (see, e.g., Kawaguchi, English Translation, “Description”, pg. 2)
Dosage forms: Oral, rectal, transdermal, subcutaneous, intravenous, and intramuscular (see, e.g., Kawaguchi, English Translation, “Description”, pg. 3)
Treatment results: Treats C. difficile infection by inhibiting growth (see, e.g., Kawaguchi, English Translation, “Discussion”, pg. 18)
Therefore, the cited reference discloses Enterococcus faecium (see, e.g., Kawaguchi, English Translation, Industrial Applicability, pg. 3) which appears to be identical to the presently claimed strain since it is suitable for inhibiting Clostridium difficile growth and is the same bacterial species as the claimed microorganism. Furthermore, it appears that the Enterococcus faecium strain, such as taught by Kawaguchi, is structurally the same to that as instantly claimed; therefore, it would also perform the intended use of treating/preventing Clostridium difficile infection.
Regarding the concentration limitations, as recited in claims 8 and 12, those working in the biological and/or pharmaceutical arts would understand that the adjustments of particular working conditions (e.g., concentrations or amounts of a compound) is deemed a matter of judicious selection and routine optimization, which is within the purview of the skilled artisan (see, e.g., MPEP 2144.05). For example, Schneider states “The compositions comprising bacterial strains are formulated into pharmaceutically acceptable dosage forms by conventional methods known to those of skill in the art. Dosage regimens are adjusted to provide the optimum desired response (e.g., the prophylactic or therapeutic effect)” (see, e.g., Schneider, pg. 99, lines 8-11). Additionally, Schneider states “Dosages of the active ingredients in the pharmaceutical compositions of the present invention can be varied so as to obtain an amount of the active ingredient which is effective to achieve the desired pharmaceutical response for a particular subject, composition, and mode of administration, without being toxic or having adverse effect on the subject” (see, e.g., Schneider, pg. 99, lines 21-24). This is motivation for someone of ordinary skill in the art to practice or test the parameter widely to find those that are functional or optimal which then would be inclusive or cover the steps as instantly claimed. Absent any teaching of criticality by the Applicant concerning the concentration, it would be prima facie obvious that one of ordinary skill in the art would recognize these limitations are result effective variable would can be met as a matter of routine optimization.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to product Schneider’s composition comprising Clostridium scindens and Blautia producta, wherein the composition also comprises Enterococcus faecium, as taught by Kawaguchi. One would have been motivated to do so because Kawaguchi teaches that Enterococcus faecium is effective in preventing invention by Clostridium difficile (see, e.g., Kawaguchi, Discussion, pg. 18). Therefore, based on the teachings of Schneider and Kawaguchi, it would have been obvious to produce a composition comprising Clostridium scindens, Blautia producta, and Enterococcus faecium for the treatment or prevention of Clostridium difficile infection. One would have expected success because Schneider and Kawaguchi both teach the treatment and/or prevention of Clostridium difficile infection through administration of bacterial compositions.
Claim 2 is rejected under 35 U.S.C. 103 as being unpatentable over Schneider and Kawaguchi as applied to claims 1, 3, 8-9, and 12-14 above, and further in view of Henn (US 2014/0147425; Date of Publication: May 29, 2014 – previously cited) and Sai (JP 2011/041474; Date of Publication: March 3, 2011 – previously cited).
The teachings of Schneider and Kawaguchi, herein referred to as modified-Schneider-Kawaguchi, are discussed above as it pertains to a composition comprising Clostridium scindens, Blautia producta, and Enterococcus faecium for the treatment or prevention of Clostridium difficile infection.
However, modified-Schneider-Kawaguchi does not teach: wherein the Clostridium scindens has a 16s rDNA sequence that is 97% or more identical to SEQ ID NO: 1 (claim 2); or wherein the Blautia producta has a 12s rDNA sequence that is 97% or more identical to any one of SEQ ID NOs: 2 to 5 (claim 2); or wherein the Enterococcus faecium has a 16s rDNA sequence that is 97% or more identical to SEQ ID NO: 6 (claim 2).
Henn’s general disclosure relates to bacterial compositions capable of decreasing and/or inhibiting the growth and/or colonization of at least one type of pathogenic bacteria (see, e.g., Henn, [0008]).
Regarding claim 2 pertaining to Clostridium scindens, Henn teaches SEQ ID NO: 979, which has 98% sequence identity to instant SEQ ID NO: 1 (see, e.g., Office Action Appendix).
Regarding claim 2 pertaining to Blautia producta, Henn teaches SEQ ID NO: 379, which has 99.1% sequence identity to instant SEQ ID NO: 2 (see, e.g., Office Action Appendix).
Sai’s general disclosure relates to “a lactic acid strain having an excelled bacteriocin-producing ability (an excellent inhibitor action against the growth of harmful microorganisms in a fermented feed) and a property suitable for producing a high-quality fermented feed” (see, e.g., Sai, English Translation, abstract).
Regarding claim 2 pertaining to Enterococcus faecium, Sai teaches SEQ ID NO: 4, which has 99.2% sequence identity to instant SEQ ID NO: 6 (see, e.g., Office Action Appendix).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to produce modified-Schneider-Kawaguchi’s composition comprising Clostridium scindens, Blautia producta, and Enterococcus faecium with rDNA sequences greater than 97%, as taught by Henn and Sai. One would have been motivated to do so because Henn teaches that Clostridium scindens and Blautia producta can be used to treat Clostridium difficile infection (see, e.g., Henn, [0070]-[0074]). Additionally, Sai teaches that Enterococcus faecium (corresponding to Sai’s SEQ ID NO:4) exhibits excellent bacteriocin production and is harmful to pathogenic microorganisms (see, e.g., Sai, English Translation, pg. 4). Therefore, based on the teachings of modified-Schneider-Kawaguchi, it would have been obvious to produce a composition comprising Clostridium scindens, Blautia producta, and Enterococcus faecium with rDNA sequences greater than 97%. One would have expected success because modified-Schneider-Kawaguchi, Henn, and Sai all teach bacterial compositions for the treatment and/or prevention of pathogenic bacterial infections.
.
Examiner’s Response to Arguments
Applicant's arguments filed 10/01/2025 have been fully considered but they are not persuasive.
In response to Applicant’s arguments pertaining to the experimental data shown in the specification and the combined strains exhibiting improved inhibitory effects (remarks, pages 8-10), these arguments are not persuasive for multiple reasons:
First, the prior art of Schneider and Kawaguchi teach that Clostridium scindens, Blautia producta, and Enterococcus faecium all inhibit the growth and survival of Clostridium difficile (see, e.g., Schneider, pg. 25, lines 14-18 & Schneider, pg. 25, lines 22-23 & Kawaguchi, English Translation, “Discussion”, pg. 18). Therefore, since Clostridium scindens, Blautia producta, and Enterococcus faecium all exhibit the same properties of inhibiting the growth and survival of Clostridium difficile, one of ordinary skill in the art would at least expect an additive, or even synergistic effect, when combining Clostridium scindens, Blautia producta, and Enterococcus faecium.
Secondly, the Applicant merely provides arguments that the claimed strains and the prior art strains taught by Schneider and Kawaguchi are different, without showing any evidence or comparison to the prior art that these strains are different. More specifically, Applicant has not provided concrete evidence, such as, for example, comparison of sequences between the instantly claimed Clostridium scindens, Blautia producta, and Enterococcus faecium strains, and the prior art strains taught by Schneider and Kawaguchi. Moreover, Applicant has not provided evidence comparing phenotype characteristics of the claimed and prior art strains to show similarities and/or differences. MPEP 716.01(C)(II) states that “Arguments presented by the applicant cannot take the place of objective evidence of the record”; therefore, Applicant’s arguments are not sufficient to overcome the prior arts of record because the Applicant has not provided objective evidence.
Thirdly, the broadest reasonable interpretation (BRI) of independent claim 1 a composition comprising lyophilized Clostridium scindens, Blautia producta, and Enterococcus faecium. Assuming arguendo that there is unexpectedness when combining Clostridium scindens, Blautia producta, and Enterococcus faecium strains for treatment of C. difficile infections, the data are not commensurate in scope with the claimed invention (see, e.g., MPEP 716.02(d)). Applicant is relying on a specific concentration of bacteria (i.e., 1x109 CFU/mL), as well as specific combinations of bacteria that include Blautia faecis and Proteus terrae, which are not part of the claimed invention according to the BRI of independent claim 1.
In response to Applicant’s arguments pertaining to the teachings of Schneider (remarks, page 10), these arguments are not persuasive for multiple reasons:
First, Schneider was not used to teach Enterococcus faecium. Instead Kawaguchi teaches Enterococcus faecium for the treatment of C. difficile infections (see, e.g., Kawaguchi, English Translation, “Discussion”, pg. 18). Furthermore, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
Secondly, Schneider does not teach away from using Clostridium scindens because Schneider teaches compositions comprising Clostridium scindens for the treatment of C. difficile infections (see, e.g., Schneider, “Summary of Invention”, pg. 3, lines 7-8, 11, 14). Moreover, Applicant’s arguments regarding Schneider’s teachings that only compositions that do not include Clostridium scindens exhibit an inhibitory effect against C. difficile would result in enablement issues for the present invention.
Regarding Applicant’s arguments pertaining to there not being motivation to combine the teachings of Kawaguchi and Schneider (remarks, page 11), these arguments are not persuasive for multiple reasons:
First, Kawaguchi teaches the use of Enterococcus bacteria, such as Enterococcus faecium, for the treatment of C. difficile infections (see, e.g., Kawaguchi, English Translation, “Discussion”, pg. 18).
Secondly, one of ordinary skill in the art would have been motivated to combine the teachings of Schneider and Kawaguchi because both of these prior art references teach compositions comprising bacteria for the treatment of C. difficile infections. Therefore, both prior art references have the same intended use and motivation.
Thirdly, regarding Applicant’s argument that Kawaguchi does not disclose or suggest the claimed combination of strains. one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). Schneider was used to teach Clostridium scindens and Blautia producta, while Kawaguchi was used to teach Enterococcus faecium.
In response to Applicant’s argument pertaining to the teachings of Henn and Sai (remarks, pages 11-12), this argument is not persuasive because Henn and Sai where merely relied upon to teach the rDNA sequences of Clostridium scindens, Blautia producta, and Enterococcus faecium. Henn and Sai were not relied upon to teach the claimed composition because the prior art of Schneider and Kawaguchi, which Henn and Sai rely upon, already teach the instantly claimed composition comprising Clostridium scindens, Blautia producta, and Enterococcus faecium for treatment of C. difficile infections. Furthermore, Henn and Sai both teach bacterial compositions comprising the claimed bacterial species for the treatment and/or prevention of pathogenic bacterial infections, including C. difficile infections, as discussed above.
Conclusion
Claims 1-3, 8-9, and 12-14 are rejected.
No claims are allowed.
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Correspondence Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to NATALIE IANNUZO whose telephone number is (703)756-5559. The examiner can normally be reached Mon - Fri: 8:30-6:00 EST.
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/NATALIE IANNUZO/Examiner, Art Unit 1653
/SHARMILA G LANDAU/Supervisory Patent Examiner, Art Unit 1653
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