DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Applicants’ Amendments
1) Acknowledgment is made of Applicants’ amendments filed 06/18/26 and 05/04/26 in response to the non-final Office Action mailed 02/04/26. The amendment filed 06/18/26 is non-compliant under 37 C.F.R § 1.121 in that it is not relative to the immediate prior compliant version, i.e., the amendment filed 05/04/26. For example: (1) Claim 32, indicated as ‘Currently Amended’, in the supplemental amendment filed 06/18/26, is identical to the amended version that was filed via the prior amendment filed 05/04/26, yet claim 32 retains the same markings with the improper status identifier; (2) New claim 52 was previously added via the amendment filed 05/04/26, yet it is presented again as a ‘new claim’ in the supplemental amendment filed 06/18/26 with an incorrect status identifier; (3) Claim 44 was amended via the amendment filed 05/04/26 to include, among other changes, the new limitations “; wherein the host is a human”, which limitations have been now removed from the claim in the amendment filed 06/18/26 without indicating the deletion of these limitations via proper markings or strikethrough as required under 37 CFR § 1.121; and (4) Claim 44 was amended via the amendment filed 05/04/26 to add the limitation “consisting of” and delete the limitations “that is at least 98% identical to”, yet these changes and markings are improperly retained in the version filed 06/18/26. Note that 37 C.F.R. § 1.121 requires that claims currently amended MUST be presented with proper markings to indicate the changes that have been made relative to the immediate prior compliant version that was entered. Further, each claim must have the correct status identifier in full compliance with 37 CFR § 1.121.
Clearly, the supplemental amendment filed 06/18/26 is non-compliant under 37 C.F.R § 1.121 and therefore said amendment/Remarks is not entered. The previous compliant amendment filed 05/04/26 and the Remarks accompanying said amendment have been entered and examined in this Office Action.
Status of Claims
2) Claims 32 and 44 have been amended via the amendment filed 05/04/2026.
Claims 36, 39, 42-43 and 48 have been canceled via the amendment filed 05/04/2026.
New claim 52 has been added via the amendment filed 05/04/2026.
Claims 32, 44 and 52 are pending.
Claims 32 and 52 are under examination.
Allowable Subject Matter Conveyed
3) The allowable subject matter and the acceptable claim language were conveyed to Applicants’ representative(s). No agreement could be reached. See attached Interview Summary.
Prior Citation of Title 35 Sections
4) The text of those sections of Title 35 U.S. Code not included in this action can be found in a prior Office Action References.
Prior Citation of References
5) The references cited or used as prior art in support of one or more rejections in the instant Office Action and not included on an attached form PTO-892 or form PTO-1449 have been previously cited and made of record.
Rejection(s) Moot
6) The rejection of claims 36, 38, 39, 42 and 43 set forth in paragraph 22 of the Office Action mailed 09/10/25 and maintained in paragraph 13 of the Office Action mailed 02/04/26 under 35 U.S.C § 102(a)(2) as being anticipated by Dong et al. (US 20200339636 A1, of record) is moot in light of Applicants’ cancellation of the claims.
7) The rejection of claims 36, 38, 39, 42 and 43 set forth in paragraph 23 of the Office Action mailed 09/10/25 and maintained in paragraph 14 of the Office Action mailed 02/04/26 under 35 U.S.C § 102(a)(1) and 35 U.S.C § 102(a)(2) as being anticipated by Shone et al. (US 20150093389 A1, of record) is moot in light of Applicants’ cancellation of the claims.
8) The rejection of claims 36, 39, 42 and 43 set forth in paragraph 16 of the Office Action mailed 02/04/26 under 35 U.S.C § 101 as being directed to a judicial exception is moot in light of Applicants’ cancellation of the claims.
Rejection(s) Withdrawn
9) The rejection of claim 32 set forth in paragraph 22 of the Office Action mailed 09/10/25 and maintained in paragraph 13 of the Office Action mailed 02/04/26 under 35 U.S.C § 102(a)(2) as being anticipated by Dong et al. (US 20200339636 A1, of record) is withdrawn in light of Applicants’ claim amendments.
10) The rejection of claim 32 set forth in paragraph 23 of the Office Action mailed 09/10/25 and maintained in paragraph 14 of the Office Action mailed 02/04/26 under 35 U.S.C § 102(a)(1) and 35 U.S.C § 102(a)(2) as being anticipated by Shone et al. (US 20150093389 A1, of record) is withdrawn in light of Applicants’ claim amendments.
11) The rejection of claim 32 set forth in paragraph 16 of the Office Action mailed 02/04/26 under 35 U.S.C § 101 as being directed to a judicial exception is withdrawn in light of Applicants’ claim amendments. A new rejection is set forth below in this Office Action to address the claim as amended.
Applicants contend that as amended, claim 32 recites “... an isolated immunogenic polypeptide consisting of SEQ ID NO: 3” and explicitly limits the fragment in terms of structure, source and length, specifically defining a fragment derived from C. difficile TcdB that is identical to SEQ ID NO: 3. Applicants submit that the present claim amendments align the pending claims with those previously allowed in the Decision on Appeal for Appeal Proceeding No. 2022-004253, U.S. application 12576750, now U.S. patent 12072338, which addressed the claims directed to protein fragments. Applicants reproduce parts of the Board’s decision and note Board’s statement that the claimed fragments exhibited markedly different characteristics compared to the native protein supported by specification data. Applicants state that similarly, the present specification at paragraph [0054] and Table 3 of the specification describes the TcdB fragments as exhibiting distinct functional and structural properties compared to the full-length holotoxin. Applicants submit that for the same reasons recognized in the cited Decision on Appeal, instant claims are directed to more than a judicial exception and are patent-eligible.
Applicants’ arguments have been carefully considered. Applicants are referred to the new rejection set forth in this Office Action to address claim 32, as amended, and the new claim 52. Applicants’ remarks related to paragraph [0054] and Table 3 of the specification are addressed in the new rejection set forth in this Office Action. With regard to Applicants’ reference to the Decision on Appeal for Appeal Proceeding No. 2022-004253, it must be noted this Board decision is not precedential. Even if it was, unlike the claims of U.S. application 12576750 (issued as U.S. patent 12072338) which recited both of the markedly different characteristics, i.e., the binding characteristics and the anti-inflammatory effect, instant claims do not recite the asserted markedly different characteristics (MDCs). Solubility, the asserted non-toxicity, and the elicitation by SEQ ID NO: 3 of antibodies specific to SEQ ID NO: 3 that are more than three logs compared to antibodies specific to TcdB-FL are not MDCs recited in instant claims. Instant claims are distinguished from those in U.S. patent 12072338.
Rejection(s) under 35 U.S.C § 101
12) 35 U.S.C § 101 states:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
13) Claims 32 and 52 are rejected under 35 U.S.C § 101 because the claimed invention is directed to a judicial exception (i.e., a law of nature, a natural phenomenon, or an abstract idea) without significantly more.
Instant claim 32, as amended, is directed to an isolated immunogenic polypeptide consisting of SEQ ID NO: 3. New claim 52 is directed to an isolated immunogenic polypeptide that is a fragment of a TcdB holotoxin of C. difficile, wherein the fragment is a polypeptide consisting of at least 375 consecutive amino acids of SEQ ID NO: 3. Because these elements are composed of matter, at least one embodiment encompassed within the broadest reasonable interpretation (BRI) of instant claims is directed to a statutory category, i.e., a composition of matter (Step 1: YES). The SEQ ID NO: 3 is described as a 381 amino acid-long fragment spanning amino acids 1072-1452 of the TcdB toxin of C. difficile that is 2367 amino acids in length. The full-length TcdB is a naturally occurring polypeptide. Accordingly, SEQ ID NO: 3 claimed in claim 32 or the fragment consisting of at least 375 consecutive amino acids of said SEQ ID NO: 3 as claimed in new claim 52 is a structurally unmodified specific region of the naturally occurring polypeptide. The full-length TcdB is the closest natural counterpart to the claimed polypeptide fragment. Clearly, SEQ ID NO: 3 or its truncated 375 amino acid-long fragment is a nature-derived or nature-based product. MPEP 2106.04(C)(II)(A) states: “....when the nature-based product is derived from a naturally occurring thing, then the naturally occurring thing is the counterpart ....”. MPEP 21-6.04(c)(II)(c) states: “The final step in the markedly different characteristics analysis is to compare the characteristics of the claimed nature-based product to its naturally occurring counterpart in its natural state, in order to determine whether the characteristics of the claimed product are markedly different. The courts have emphasized that to show a marked difference, a characteristic must be changed compared to nature, and cannot be an inherent or innate characteristic of the naturally occurring counterpart or an incidental change in a characteristic of the naturally occurring counterpart”. Being immunogenic is the only characteristic recited in instant claims. Both the natural counterpart and the SEQ ID NO: 3 or its truncated 375 amino acid-long fragment are long enough to be immunogenic. The full-length TcdB is expected to induce an immune response to SEQ ID NO: 3 or to at least 375 consecutive amino acids of SEQ ID NO: 3 since each is comprised within the full-length TcdB. Applicants refer to paragraph [0054] and Table 3 of the as filed specification and assert that the TcdB fragments exhibit distinct functional and structural properties compared to the full-length holotoxin. Paragraph [0054] and Table 3 of the specification referred to by Applicants indicate that mice were subcutaneously injected with the soluble TD1, i.e., SEQ ID NO: 3, with or without an adjuvant(s) such as alum. Paragraph [0054] states [Emphasis added]:
..... Immunization with a non-toxic segment of C. difficile TcdB induces high antibody levels in mice. Antibody levels are boosted by greater than 3 logs. The immune response is specific against a 381 aa immunogen (compared to the full-length toxin, which is 2367 aa). The induced antibodies against the 381 aa immunogen also react to the full length toxin.
Table 3 of the as-filed specification indicates that TD1 (SEQ ID NO: 3) is soluble and this soluble TD1 is capable of inducing an immune response, not that the TcdB natural counterpart that comprises said SEQ ID NO: 3 does not do so. Antibodies induced against the 381aa immunogen reacting with TcdB-FL (full length) toxin is an expected intrinsic activity since the 381aa immunogen is a part of or is comprised within the full length TcdB. The immunogenicity characteristic of the claimed polypeptide is the handiwork of nature and is inseparable therefrom. Therefore, being immunogenic as recited is not a markedly different characteristic (MDC) compared to the natural counterpart. Furthermore, paragraph [0054] and Table 3 provide no data with regard to any characteristics or properties, let alone markedly different characteristics (MDCs), of the polypeptide fragment consisting of 375 consecutive amino acids of SEQ ID NO: 3. There appears to be no evidence that the toxicity of TcdB is because of SEQ ID NO: 3 and not because of one or more other regions of TcdB. Accordingly, the claims are directed to a judicial exception (Step 2A Prong One). Next, the claims as a whole are analyzed to determine whether any additional element, or a combination of elements, is sufficient to ensure that the claims amount to significantly more than the exceptions. No additional element(s), such as alum, is present with the claimed SEQ ID NO: 3 or a 375 amino acid-long fragment of SEQ ID NO: 3. The claims as a whole do not recite additional elements that integrate the recited judicial exception into a practical application of the judicial exception (Step 2A, Prong 2). The claims as a whole do not include additional elements that are sufficient to amount to significantly more than the judicial exception (Step 2B). Therefore, instant claims are not directed to a patent eligible subject matter.
The rationale for this determination is formed in view of the 2019 PEG, the 2015 Update of the 2014 Interim Guidance on Patent Subject Matter Eligibility (79 FR 4618) (hereafter Interim Eligibility Guidance) dated 16 December 2014, the Life Sciences Examples issued in May 2016, and in view of Myriad v Ambry, CAFC 2014-1361, -1366, 17 December 2014. The unpatentability of laws of nature was confirmed by the U.S. Supreme Court in Mayo Collaborative Services v. Prometheus Laboratories, Inc., No. 10-1150 (March 20, 2012). The unpatentability of natural products was confirmed by the U.S. Supreme Court in Association for Molecular Pathology v. Myriad Genetics, Inc., 569 U. S. (June13, 2013).
Conclusion
15) No claims are allowed.
16) Applicants’ amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicants are reminded of the extension of time policy as set forth in 37 C.F.R 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 extension fee pursuant to 37 C.F.R 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
17) Any inquiry concerning this communication or earlier communications from the Examiner should be directed to S. Devi, Ph.D., whose telephone number is (571) 272-0854. A message may be left on the Examiner’s voice mail system. The Examiner is on a flexible work schedule, however she can normally be reached Monday to Friday from 8.00 a.m. to 4.00 p.m. (EST). If attempts to reach the Examiner by telephone are unsuccessful, the Examiner’s Supervisor, Jeffrey Stucker, can be reached at (571) 272-0911. The fax phone number for the organization where this application or proceeding is assigned (571) 273-8300.
18) Information regarding the status of an application may be obtained from Patent Center. Status information for unpublished applications is available through Patent Center or Private PAIR to authorized users only. Should you have questions about access to Patent Center or the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). 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.
/S. DEVI/
S. Devi, Ph.D.Primary Examiner
Art Unit 1645
August, 2026
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