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 .
Status of Claims
The amendment filed on 07/23/2026 amended claims 1, 9, and 10 and cancelled claims 2-6, 8, and 12-24. Claims 1, 7, and 9-11 are pending and will be examined on the merits.
Response to Amendment
The amendment filed 07/23/2026 in response to the office action mailed 02/26/2026 is acknowledged. The rejections set forth under 35 USC 102 are withdrawn for the following reasons: The amended claims are no longer addressed by the art used for the 102 rejection and the double patenting rejections are rendered moot by the amended claims.
New, maintained or modified rejections are set forth below, as necessitated by the amendments. Responses to arguments follow.
New Claim Rejections - 35 USC § 112
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 1, 7, and 9-11 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.
Amended claim 1 recites “administering to the mammal a Candida Als3 or a fragment thereof”. This is unclear as the term ‘Als3’ is not properly defined by the claim. Examiner suggests amending the claim to recite ‘a Candida Als3 peptide…’ or ‘a Candida Als3 protein…’. Claim 10 recites the same language, and is therefore unclear. Claims 7, 9, and 11 inherit this rejection as they do not clarify the term.
Additionally, if Als3 is an abbreviation, the first recitation of an abbreviation in the claims should be preceded by the full meaning of the abbreviated term so as to clearly convey what the abbreviation means (for example, agglutinin-like sequence (Als) protein, as written in cancelled claim 2). Appropriate correction is required.
New Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 1, 7, 9, and 10 is/are rejected under 35 U.S.C. 103 as being unpatentable over Edwards et al. (Clinical Infectious Diseases (2018); 66(12):1928–36) and Casadevall et al. (Clinical Infectious Diseases (2018); 66(12):1937–9) in view of Goethel et al. (J Physiol 596.17 (2018) pp 3869–3882) and Gu et al. (Medicine in Microecology 3 (2020) 100008).
The instant claims are drawn to a method of reducing colon tissue damage in a mammal having inflammatory bowel disease (IBD) characterized with Candida infection, comprising administering to the mammal a Candida Als3 peptide or a fragment thereof. Dependent claims specify the mammal is human, the IBD is Crohn’s disease or colitis, and the peptide is administered via intramuscular, subcutaneous, intradermal, oral, sublingual, or inhalation administration methods, and additionally as a booster dose.
Edwards et al. teach a vaccine comprising a recombinant Als3 antigen and aluminum hydroxide, NDV-3A (see clinical trial material, page 1929, col. 1). Edwards et al. additionally teach this vaccine administered to human patients with vulvovaginal candidiasis (VVC) intramuscularly (see page 1929, col. 2).
Edwards et al. do not teach the use of this vaccine in a method of reducing colon tissue damage in a mammal with IBD characterized by Candida infection. However, Casadevall et al., commentary on the Edwards et al. study, disclose that the NDV-3A vaccine, comprising a recombinant Candida albicans Als3 antigen (see page 1937, col. 1 into col. 2), reduces symptoms of recurrent vulvovaginal candidiasis (RVVC) caused by C. albicans. Casadevall et al. discuss that the target population of the NDV-3A vaccine is women already infected with C. albicans (page 1937, col. 2), and that the vaccine was not used to simply prevent colonization. Casadevall et al. disclose that RVVC is mediated by an overexuberant host inflammatory response, more similar to allergic inflammation than local, invasive, fungal disease (pg 1937, col. 3). Casadevall et al. disclose that the vaccine is administered systemically, but still mediates protection at a mucosal site. Casadevall et al. teach that the NDV-3A vaccine likely controls symptoms of VVC via antibody immunity, as vaccine-elicited antibodies mediate protection by controlling the inflammatory response, especially via Fc receptors (page 1938, col 1). Casadevall et al. emphasize that the NDV-3A vaccine did not affect fungal burden, indicating the vaccine does not mediate fungal elimination, but control of an overactive immune response (pg 1938, col. 1-2), or, possibly, expression of inflammatory antigens by C. albicans. Casadevall et al. encourages use of similar vaccines for commensal organisms associated with states of disease (pg. 1938, col. 3).
Goethel et al. teach the immune response in IBD (see section “Involvement of the immune system in IBD”, page 3872-3873). Goethel et al. teach that inflammation in IBD can be triggered by a variety of sources, features high levels of pro-inflammatory cytokines such as IL-1β, TNFα, IL-6, and IL-12, believed to be the result of uncontrolled inflammatory responses to pathogens. Goethel et al. teach that tissue damage in IBD is often associated with increased neutrophils and monocytes (see page 3873, col. 1). Gu et al. teach that C. albicans has been implicated in Crohn’s disease as early as the 1980s (see Table 1 and section 2.4, page 3, left column), including high titers of antibodies against Candida species found in these patients, indicating that Candida antigens elicit an adaptive immune response linked to intestinal inflammation. Moreover, the role of Als3 is known to be inflammatory, as it mediates passive uptake by host intestinal epithelial cells (section 2.2, page 3, column 1) and is important for switching from asymptomatic commensal yeast cells to hyphae, which can trigger inflammatory signaling pathways and tissue invasion (section 2.3, pg 3, col. 2). Goethel et al. teach that the physical barrier of epithelial cells between the lumen and the mucosal tissue layers is a primary line of defense against an overactive immune response, and when this barrier is breached, inflammation can increase rapidly due to the activation of immune cells by MAMPs (microbe-associated molecular patterns) and PRRs (pattern-recognition receptors), including TLRs (Toll-Like Receptors) (see page 3875, col. 1).
Given the context provided by Goethel et al. and Gu et al., one of ordinary skill in the art will recognize that tissue damage in IBD characterized by Candida infection is likely mediated by the immune response to Candida antigens. This information would motivate one of skill in the art to target Candida antigens in an effort to control the immune response flares. Therefore, it would be obvious to one of ordinary skill in the art to administer a known vaccine to a Candida antigen, such as the NDV-3A vaccine, in an attempt to control the inflammatory response to Candida antigens. One would have at least a motivation to try, as well as a reasonable expectation of success, as the NDV-3A vaccine has been shown to alleviate inflammation in a different mucosal infection hallmarked by an overactive immune response to Candida antigens; namely, RVVC, as disclosed in Edwards et al. and Casadevall et al. RVVC is characterized by Candida infection of a mucosal tissue, and the NDV-3A vaccine is able to improve symptoms of inflammation, even without altering microbial burden. The NDV-3A vaccine was also administered systemically, and still had an advantageous effect on the distal mucosal tissue affected by RVVC. Therefore, it would be obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to use the NDV-3A vaccine, deemed safe and effective as a RVVC treatment, to reduce tissue damage in a different disease characterized by Candida infection at a mucosal site; i.e., IBD. Therefore, claims 1, 7, 9, and 10 are obvious over Edwards et al. and Casadevall et al. in view of Goethel et al. and Gu et al.
Claim(s) 1, 7, and 9-11 is/are rejected under 35 U.S.C. 103 as being unpatentable over Edwards et al. and Casadevall et al. in view of Goethel et al. and Gu et al as applied to claims 1, 7, 9, and 10 above, and further in view of Schmidt et al. (Vaccine 30 (2012) 7594-7600).
The teachings of Edwards et al. and Casadevall et al. in view of Goethel et al. and Gu et al. regarding claims 1, 7, 9, and 10 can be seen above. These sources do not teach administration of a booster dose, as recited in instant claim 11. However, Schmidt et al. do teach a booster dose of the NDV-3A vaccine, the same vaccine taught by Edwards et al. Additionally, Schmidt et al. state “the second dose resulted in a significant boost of IgG and IgA1 titers in >70% of subjects…” in the abstract. Therefore, it would have been obvious to one of ordinary skill in the art of vaccination before the effective filing date of the claimed invention to provide a booster dose in concert with the method of Edwards et al. in order to induce a significant improvement in immune response, including a boost in antibody production. One would have reasonable expectation of success because the vaccines of Schmidt and Edwards et al. are the same, with both containing a Candida albicans Als3 protein. Therefore, it would have been obvious, before the effective filing date of the claimed invention, to provide a booster dose of the method of ‘120 in order to improve immune responses and produce more antibodies, thereby further reducing colon tissue damage. Therefore, claims 1, 7, and 9-11 are obvious over Edwards et al. and Casadevall et al. in view of Goethel et al. and Gu et al., and further in view of Schmidt et al.
Response to Arguments
Applicant’s arguments with respect to claim(s) 1, 7, and 9-11 have been considered but are moot because the new ground of rejection does not rely on any reference applied in the prior rejection of record for any teaching or matter specifically challenged in the argument.
Applicant's arguments filed 07/23/2026 have been fully considered but they are not persuasive. Applicant argues that the amended claims are non-obvious as the claimed invention is based on unexpected results, presented in the instant application. Specifically, Applicant points to Als3 as being expected to have limited ability to reduce fungal burden, recited on page 3 of the arguments. Applicant points to paragraph [00274] of the instant specification to show that vaccination with NDV-3A (noted by the Examiner to be the same as recited in Edwards et al.) generated a considerable immune response in terms of antibody production, but did not affect C. albicans morphology or intestinal lumen fungal burden when the subject was already infected. Applicant further argues that “the ability of Als3 to reduce colon tissue damage without reducing intestinal lumen fungal burden was surprising…” on page 4, paragraph 2 of the remarks. In light of the section of the specification cited, Examiner is interpreting this statement as ‘the ability of NDV-3A vaccination to reduce colon tissue damage…’. Examiner points Applicant to the 103 rejection above, where Edwards et al. and Casadevall et al. disclose that vaccination with NDV-3A also did not reduce fungal burden in RVVC cases, indicating that this is a known result with NDV-3A and thus cannot be considered unexpected. Additionally, Casadevall et al. recite that antibodies against Als3 mediate the immune response and reduce symptoms of active VVC (page 1938, column 1), indicating that the immune response to NDV-3A eliciting antibody production is also known. Furthermore, as recited in the 103 above, Goethel et al. discloses that tissue damage in IBD is primarily caused by the immune response reacting to pathogens. Casadevall et al. discloses that the NDV-3A vaccine can, via antibodies, mediate a reduction in the inflammatory response to Candida and decrease the immune response at the mucosal site without affecting the microbial burden itself. Therefore, the observation that tissue damage, a response to an overactive immune response, is lessened by NDV-3A vaccination, while the fungal burden does not change, is not unexpected in view of the state of the art at the time of filing. Therefore, Applicant’s argument is unconvincing. See 103 rejection above for further details.
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.
Claims 1, 7, and 9-11 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-9 of U.S. Patent No. 9,364,539 in view of Edwards et al., Casadevall et al., Goethel et al., and Gu et al.
‘539 claim 1 discloses a method of vaccinating a mammalian host against C. albicans comprising administering to said host a composition comprising a C. albicans Als3 polypeptide. ‘539 claim 8 specifies the mammal is human, as in instant claim 7, ‘539 claim 6 recites a booster dose, as in instant claim 11, and ‘539 claim 2 recites subcutaneous administration, as in instant claim 7.
‘539 does not disclose a method of reducing colon tissue damage in a mammal with IBD characterized by Candida infection comprising administering the same vaccine. However, in light of Edwards et al. and Casadevall et al., one of ordinary skill in the art would know that vaccinating a mammal against C. albicans with an Als3 peptide can result in a reduction of inflammation at a mucosal tissue. One would be motivated to apply this knowledge to IBD, a mucosal inflammatory disease, in light of Goethel et al. and Gu et al., which, in combination, disclose the role of inflammation triggered by C. albicans in IBD tissue damage (see 103 above under paragraph 10 for the full disclosures of Edwards et al., Casadevall et al., Goethel et al., and Gu et al.). Therefore, the instant claims are obvious over ‘539 in view of Edwards et al., Casadevall et al., Goethel et al., and Gu et al.
Response to Arguments
Applicant’s arguments, see pages 4-5, filed 07/23/2026, with respect to claims 1-12 have been fully considered and are persuasive. The double patenting rejections over U.S. Patent No. 10,653,757, U.S. Patent No. 8,541,008, U.S. Patent No. 10,300,120, U.S. Patent No. 10,130,691, U.S. Patent No. 10,160,790, U.S. Patent No. 8,709,446, U.S. Patent No. 12,324,830, and copending Application No. 19/204,363 have been withdrawn for the following reasons:
The claims of ‘757 and ‘120 are drawn to methods of treating skin abscesses caused by S. aureus. There is no obvious reason the same method would treat IBD tissue damage.
The claims of ‘008 are drawn to a method of vaccinating a mammalian host comprising administering an Als1 peptide. This limitation was removed from the claims upon amendment and no longer reads on the instant claims.
The claims of ‘691, ‘790, and ‘446 are drawn to a composition or a method of treating with said composition comprising an HYR1 peptide. This limitation was removed from the claims upon amendment and no longer reads on the instant claims.
The claims of ‘830 and pending Application ‘363 are drawn to a method of treating or preventing a Candida auris infection with an Als3 peptide. This does not read on the instant claims as C. auris is not an established pathogen in IBD.
The nonstatutory double patenting rejection over 9,364,539 is withdrawn, but reissued as an obviousness-type rejection in light of the amendments.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Amelia Stephens whose telephone number is (571)272-1006. The examiner can normally be reached M-F 8-5 EST.
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/AMELIA STEPHENS/Examiner, Art Unit 1645
/ANNE M. GUSSOW/Supervisory Patent Examiner, Art Unit 1683
