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 .
DETAILED ACTION
Claim Status
The amendment on December 23, 2025 is acknowledged. Claims 4-13 are currently pending. There are no new claims and claims 14-23 are withdrawn. Claims 1-3 are canceled. Claims 4-13 will be examined on the merits herein.
Election/Restrictions
Applicant’s election without traverse of Group I (claims 4-13) in reply filed on December 23, 2025 is acknowledged. Claim 14-23 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on December 23, 2025.
Priority
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55. However, certified English copies have not been filed and therefore the examiner cannot determine if it discloses the now-claimed invention. For the purpose of applying prior art, the effective filing date is October 9, 2022, the date that PCT/CN2022/124020 was filed.
Information Disclosure Statement (IDS)
At the time of the instant Office action, no information disclosure statement (IDS) had been received.
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.
Claims 4-7 and 10 are rejected under 35 U.S.C. 103 as being unpatentable over NCT03435952 (ClinicalTrials.gov number, NCT03435952, public record history available: February 9, 2018; hereafter PTO-892) in view of Wei et al. (US 9,962,412 B2, hereafter PTO-892).
The non-patent literature, ClinicalTrials.gov ID: NCT03435952 (submitted and recorded in September 9th 2018; see document) teaches treating solid tumors with spores of Clostridium bacteria and pembrolizumab, which is pertinent to claim 4. See for examples pages 6-7 of the attached printout. NCT03435952 also teaches that pembrolizumab is to be injected, which is pertinent to claim 10; see NCT03435952 page 7, first paragraph under Study Drug Administration. However, NCT03435952 teaches spores from Clostridium Novyi-NT, not Clostridium ghonii as recited in claim 4, and NCT03435952 does not teach the particular strains recited in claim 5-7.
Wei teaches that the particular strains recited in claims 5-7 can be used to treat cancers; see for example column 27 claims 1-3, column 28 claims 18-21, and column 4 lines 5-29. Wei also teaches that antibodies for treating cancer can be co-administered; see column 17 lines 32-43, column 17 line 58 – column 18 line 3.
It would have been obvious to one of ordinary skill in the art to modify the teachings of NCT03435952 by selecting the particular Clostridium strains disclosed by Wei, thereby arriving at the invention of claims 4-7 and 10. Since the Clostridium spores of NCT03435952 and those of Wei were both shown in the prior art to be effective in treating cancer, it would have been obvious to substitute these known equivalents; see MPEP 2144.06.
Claims 8-9 are rejected as unpatentable under 103 over NCT03435952 (ClinicalTrials.gov number, NCT03435952, public record history available: February 9, 2018; hereafter PTO-892) in view of Wei et al. (US 9,962,412 B2, hereafter PTO-892) as applied to claims 4-7 and 10 above, and further in view of OPS Diagnostics.
The reasons why claims 4-7 would have been obvious over NCT03435952 in view of Wei are set forth above. However, neither reference teaches freeze-dried powder with 1% sucrose as in claim 8 or the particular protocol in claim 9.
OPS diagnostics teaches bacterial freeze-drying protocols, see web address page) and sucrose, which is pertinent with claims 8-9. OPS Diagnostics, Bacterial Freeze-Drying protocol also suggests that minor adjustments can be made to improve the efficiency in the procedure which is pertinent with claim 9.
It would have been obvious to one of ordinary skill in the art to adapt the teachings of OPS diagnostics, Bacterial Freeze-Drying protocol to Freeze-Drying spores of Clostridium ghonii as in claim 8 and 9. Since, OPS Diagnostics, Bacterial Freeze-Drying protocol teaches several alternatives and modifications in the procedure that can be adapted to any bacteria, it would have been obvious to substitute these known equivalents; see MPEP 2144.06.
PNG
media_image1.png
879
1371
media_image1.png
Greyscale
Claims 11-13 are rejected as unpatentable under 103 over NCT03435952 (ClinicalTrials.gov number, NCT03435952, public record history available: February 9, 2018; hereafter PTO-892) in view of Wei et al. (US 9,962,412 B2, hereafter PTO-892) as applied to claims 4-10 above, and further in view of Reference ID: 4277239 (labeling information, https://www.accessdata.fda.gov, January 12, 2020 hereafter PTO-892).
The reasons why claims 4-10 would have been obvious over NCT03435952 in view of Wei are set forth above. However, neither reference teaches Clostridium ghonii combined with pembrolizumab as in claim 11 or the particular solvent as in claim 12 and 13.
Wei teaches the therapeutically effective amount of a spores from derivative strain of Clostridium ghonii to treat solid tumors in humans is about 106 CFU to about 1014 CFU per dose (see page 21, column 17, lines 22-25) and NCT03435952 teaches the use of pembrolizumab in combination with a starting dose of 104 spores of clostridial bacteria (see page 13), which is pertinent to claim 11.
The FDA access data, Reference ID: 4277239 teaches dosage and administration of pembrolizumab is dependent on type/form of cancer and patient conditions such as age and prior health conditions. The FDA access data, Reference ID: 4277239 also teaches the reconstitution of pembrolizumab, lyophilized powder using sterile water and preparation for intravenous infusion as the reconstituted required vial (s) of pembrolizumab transferred into an intravenous bag containing 0.9% Sodium Chloride Injection or 5% Dextrose injection at the final concentration of 1mg/mL to 10 mg/mL (diluted concentration), which is pertinent to claims 11-13. See page 7, paragraph 2.12.
PNG
media_image2.png
405
1431
media_image2.png
Greyscale
It would have been obvious to one of ordinary skill in the art to modify the teachings of FDA access data, Reference ID: 4277239 and the amount clostridial spores (CFUs) disclosed by Wei because NCT03435952 already taught the use of clostridial spores with pembrolizumab to be a strategy to treat cancer, thereby arriving at the invention of claim 11-13. It would have been obvious to substitute these known equivalents; see MPEP 2144.06.
KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007), discloses that the simple substitution of one known element for another to obtain predictable results is obvious unless its application is beyond that person's skill. KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007) also discloses that "the combination of familiar elements according to known methods is likely to be obvious when it does no more than yield predictable results". In the instant case, NCT03435952 teaches a product (and a method) that only differs from the claimed invention by the substitution of a single element (i.e. substitution of the species of clostridial spores); the substituted element (i.e. clostridial spores) was already known to be used to treat cancer, therefore no change in the function of the substituted element occurred; and one of ordinary skill in the art would be capable of substituting one Clostridium species for another with a reasonable expectation of success (i.e. the substitution of the element would lead to predictable results). Therefore, the claimed invention is prima facie obvious in view of the teachings of the prior art, absent any convincing evidence to the contrary.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claim 4-7 and 10 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-5 of U.S. Patent No. US 10, 314,809 B2 in view of Xing. This is s nonstatutory double patenting rejection.
Claims 1-5 of Patent No. US 10,314,809 B2 recite pharmaceutical compositions including the particular strains recited in claims 5-7 and encompassed by claim 4. However, Patent No. US 10, 314,809 B2 does not claim pembrolizumab.
NCT03435952 teaches that pembrolizumab can be combined with clostridium spores for treating cancers, which is pertinent to claims 4-7. NCT03435952 also teaches that pembrolizumab can be injected, as in claim 10.
Therefore, it would have been obvious to a PHOSITA to modify the invention claimed in Patent No. US 10, 314,809 B2 to include pembrolizumab as taught by NCT03435952, arriving at the invention of claims 4-7 and 10.
See MPEP 2144(II): “The strongest rationale for combining references is a recognition, expressly or impliedly in the prior art … that some advantage or expected beneficial result would have been produced by their combination.
Reasonable expectation of success would be expected because Patent No. US 10,314,809 B2 specifically suggests using anticancer drug combining spores of Clostridium ghonii for treating cancer and does not specify any medicine that should not be used.
Also, KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007), discloses that the simple substitution of one known element for another to obtain predictable results is obvious unless its application is beyond that person's skill. KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007) also discloses that "the combination of familiar elements according to known methods is likely to be obvious when it does no more than yield predictable results". In the instant case, the prior art (the claims of US 10, 314,809 B2) teaches a product (and method) that only differs from the claimed invention by the substitution of a single component (i.e. substitution of the anticancer drug used); the substituted element (i.e. pembrolizumab) was already known and known to function as an anticancer drug, therefore no change in the function of the substituted element occurred; and one of ordinary skill in the art would be capable of choosing anticancer drugs disclosed as being useful with a reasonable expectation of success (i.e. the substitution of the element would lead to predictable results), particularly because NCT03435952 teaches that pembrolizumab was known to treat cancer. Therefore, the claimed invention is prima facie obvious in view of the teachings of the prior art, absent any convincing evidence to the contrary.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to PRICILA HAUK TEODORO whose telephone number is (571) 272-2784. The examiner can normally be reached M-F 6:15AM-3:15PM.
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, Daniel Kolker can be reached at (571) 272-3181. 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.
/PRICILA NMN HAUK TEODORO/ Examiner, Art Unit 1645
/DANIEL E KOLKER/Supervisory Patent Examiner, Art Unit 1645