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 .
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 02/10/2026 was filed after the mailing date of the non-final on 11/10/2025. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Status of the Claims
Claims 1, 6, and 9-26 are pending in this application. Claims 2-5 and 7-8 have been cancelled by Applicant.
Claim Interpretation
The specification defines immune-DASH inhibitors as “potent inhibitors of the post-proline cleaving enzymes (PPCEs) DPP4, DPP8 and DPP9” (see [0002]).
Claim Objections
Claim 18 is objected because Examiner believes Applicant intended for claim to read: “…treatment protocol comprising one or more additional chemotherapeutic agents…”.
Appropriate correction is required.
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 1, 6, 9-15, 19-22, 24, and 26 are rejected under 35 U.S.C. 103 as being unpatentable over Walsh et al. (PLOS; 2015, 8, e58860, 13 pages) (“Walsh”); in view of Gee et al. (Anticancer Research, 2009, 29, 3769-3776) (“Gee”).
Regarding claims 1, 6, 9-15, 19-22, 24, and 26, Walsh teaches that Val-boroPro mediates tumor eradication by accelerating the expansion of tumor specific T cells; T cells primed by tumor during Val-boroPro treatment demonstrate increased capacity to reject tumors following adoptive transfer without further treatment of the recipient (abstract). Walsh teaches Val-boroPro as a post-proline cleaving enzyme (PPCE) inhibitor, like DPP IV (a prototypical extracellular member of the PPCE family associated with CD26 on the cell surface) and DPP 8/9 – reading on immune-DASH inhibitor (see claim interpretation) (see page 1, col. 2, last para.; and page 2, col. 1, top 4 lines). Walsh teaches dipeptide boronic acids (DBAs) like Val-boroPro potently inhibit PPCEs (page 2, col. 1, para. 2). Val-boroPro has potent adjuvant properties resulting in an effective therapeutic vaccine (abstract). Welsh discloses mice challenged with MB49 cell lines, which correspond to bladder carcinoma.
While Walsh does not teach coadministration of their immune-DASH inhibitor (Val-boroPro) in combination with a COX-2 inhibitor; the teachings of Gee are relied upon for these disclosures.
Gee teaches that COX-2 has been identified in multiple tumor types including bladder cancer, and further teaches celecoxib and rofecoxib as COX-2 inhibitors (abstract; and page 3771, col. 2, last para.).
Therefore, regarding instant claims 1, 6, 9-15, 19-22, 24, and 26, it would have been prima facie obvious to one of ordinary skill prior to the effective filing date of the claimed invention to administer a COX-2 inhibitor and Val-boroPro (an immune-DASH inhibitor) for enhancing an immune response against a tumor. One of ordinary skill would have been motivated to do so with a reasonable expectation of success because Walsh discloses Val-boroPro as a potent PPCE inhibitor, and teaches that Val-boroPro mediates tumor eradication by accelerating the expansion of tumor specific T cells, that T cells primed by tumor during Val-boroPro treatment demonstrate increased capacity to reject tumors following adoptive transfer without further treatment of the recipient (in mice challenged with MB49 – bladder carcinoma); further because Gee teaches celecoxib and rofecoxib as COX-2 inhibitors and teaches that COX-2 has been identified in multiple tumor types including bladder cancer.
Applicant is advised that, with respect to a mixture of the two claimed reagents, the courts have found that “[i]t is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art (In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980).” See MPEP2144.06. It is therefore obvious to provide a mixture of the two agents.
Further regarding claims 9-15, it is noted that the subject matter of a properly construed claim is defined by the terms that limit its scope. It is this subject matter that must be examined.As a general matter, the grammar and intended meaning of terms used in a claim will dictate whether the language limits the claim scope. Language that suggests or makes optional but does not require steps to be performed or does not limit a claim to a particular structure does not limit the scope of a claim or claim limitation. “Wherein” clauses are examples of language that may raise a question as to the limiting effect of the language in a claim. See MPEP 2103 I.C. and MPEP § 2111.04.
It is also noted that a “wherein” clause, such as that in claims 9-15, must give “meaning and purpose to the manipulative steps.” See, MPEP § 2111.04.
Further regarding claims 9-15, the instant specification defines “therapeutically effective amount” (TEA) as an amount that alleviates a symptom, ameliorates a condition, or slows the onset of a disease [0408]. The spec. further states that TEA will vary according to weight, sex, age, and medical history – suggesting that all immune-DASH inhibitors (see claim interpretation) will have the same TEA range as long as the aforementioned parameters are considered. The instant spec. states the compounds may be administered as part of their methods in doses ranging from 0.1 to 5 mg/kg /day [0412], thus suggesting that these dosage amounts will be therapeutically effective at carrying out the intended response stated in the claims.
Walsh discloses administration of 20 µg of Val-boroPro to mice (see Figure 1, page 3). Walsh also discloses immune assays of T cell and macrophage depletion (see pages 2-4) and discloses that Val-boroPro Increases Serum IL-5 and Induces IL-17 Production by Antigen-primed. Gee teaches that celecoxib has been reported to inhibit the COX-2 enzyme with an IC50 of less than 1 μM and that serum concentrations of only 2-3 μM celecoxib were required to inhibit the growth of colon carcinoma xenografts in nude mice (page 3774, col. 1, 2nd to last para.). Therefore, one of ordinary skill would expect, with a reasonable expectation of success, that the administration of Walsh’s and Gee’s combined treatment would result in the instantly claimed outcomes, as the compounds being administered are the same as the claimed compounds (COX-2 inhibitor and immune-DASH inhibitor).
Per MPEP 2112(I): "[T]he discovery of a previously unappreciated property of a prior art composition, or of a scientific explanation for the prior art’s functioning, does not render the old composition patentably new to the discoverer." Atlas Powder Co. v. IRECO Inc., 190 F.3d 1342, 1347, 51 USPQ2d 1943, 1947 (Fed. Cir. 1999). Thus, the claiming of a new use, new function or unknown property which is inherently present in the prior art does not necessarily make the claim patentable. In re Best, 562 F.2d 1252, 1254, 195 USPQ 430, 433 (CCPA 1977). In In re Crish, 393 F.3d 1253, 1258, 73 USPQ2d 1364, 1368 (Fed. Cir. 2004), the court held that the claimed promoter sequence obtained by sequencing a prior art plasmid that was not previously sequenced was anticipated by the prior art plasmid which necessarily possessed the same DNA sequence as the claimed oligonucleotides. The court stated that "just as the discovery of properties of a known material does not make it novel, the identification and characterization of a prior art material also does not make it novel."
Regarding claim 19, Walsh teaches Val-boroPro has potent adjuvant properties resulting in an effective therapeutic vaccine (abstract) – thus reading on the instantly claimed treatment being used as part of a protocol which comprises a tumor vaccine.
Claims 23 and 25-26 are rejected under 35 U.S.C. 103 as being unpatentable over Walsh et al. (PLOS; 2015, 8, e58860, 13 pages) (“Walsh”); in view of Gee et al. (Anticancer Research, 2009, 29, 3769-3776) (“Gee”); as applied to claims 1, 6, 9-15, 19-22, 24, and 26; further in view of Meanwell et al. (J. Med. Chem. 2011, 54, 2529–2591) (“Meanwell”).
The teachings of Walsh and Gee are disclosed above and incorporated herein.
Walsh teaches dipeptide boronic acids (DBAs) like Val-boroPro (shown below) (page 2, col. 1, para. 2).
PNG
media_image1.png
115
193
media_image1.png
Greyscale
While Walsh and Gee do not disclose the instant fluorinated Val-boroPro derivative (see below); the teachings of Meanwell are relied upon for these disclosures.
PNG
media_image2.png
88
133
media_image2.png
Greyscale
Meanwell teaches that the design of bioisosteres frequently introduces structural changes that can be beneficial depending on the context, with size, shape, electronic distribution, polarizability, dipole, polarity, lipophilicity, and pKa potentially playing key contributing roles in molecular recognition and mimicry. In the contemporary practice of medicinal chemistry, the development and application of bioisosteres have been adopted as a fundamental tactical approach useful to address a number of aspects associated with the design and development of drug candidates (abstract). Meanwell specifically teaches H and F as classical monovalent bioisosteres (see table 1, page 2530); The unique properties of fluorine have led to its widespread application in drug design as an isostere for hydrogen, since incorporation of this halogen can productively modulate a range of properties of interest to medicinal chemists (page 2531, col. 1, last para.).
Therefore, regarding claims 23 and 25-26, it would have been prima facie obvious to one of ordinary skill prior to the effective filing date of the claimed invention administer the instant fluorinated DBA compound shown above, as taught by Walsh and Gee in view of Meanwell. One of ordinary skill would have been motivated to do so in view of Walsh and Gee’s disclosure of a treatment combination comprising Val-boroPro and a COX-2 inhibitor for the enhancement of an immune response against a tumor; further in view of Meanwell’s teaching that the design of bioisosteres introduces beneficial changes in lipophilicity and potency etc., and their teaching that H and F are classical monovalent bioisosteres, rendering substitution of one for the other as an obvious transformation in medicinal chemistry.
Applicant is advised that similar properties may normally be presumed when compounds are very close in structure. Dillon, 919 F.2d at 693, 696, 16 USPQ2d at 1901, 1904. See also In re Grabiak, 769 F.2d 729, 731, 226 USPQ 870, 871 (Fed. Cir. 1985) (“When chemical compounds have very close structural similarities and similar utilities, without more a prima facie case may be made.”). Thus, evidence of similar properties or evidence of any useful properties disclosed in the prior art that would be expected to be shared by the claimed invention weighs in favor of a conclusion that the claimed invention would have been obvious. Dillon, 919 F.2d at 697-98, 16 USPQ2d at 1905; In re Wilder, 563 F.2d 457, 461, 195 USPQ 426, 430 (CCPA 1977); In re Linter, 458 F.2d 1013, 1016, 173 USPQ 560, 562 (CCPA 1972) (see MPEP 2144.08(d)).
Claims 16-18 are rejected under 35 U.S.C. 103 as being unpatentable over Walsh et al. (PLOS; 2015, 8, e58860, 13 pages) (“Walsh”); in view of Gee et al. (Anticancer Research, 2009, 29, 3769-3776) (“Gee”); as applied to claims 1, 6, 9-15, 19-22, 24, and 26; further in view of Zang et al. (Clin. Cancer Res., 2007, 13(18), 5271-5279 – previously cited) (“Zang”).
The teachings of Walsh and Gee are disclosed above and incorporated herein.
While Walsh and Gee do not specifically disclose coadministration of a checkpoint inhibitor (claim 16), or a costimulatory molecule (claim 17), or an additional chemotherapeutic agent (claim 18); the teachings of Zang are relied upon for these disclosures.
Zang teaches that absence of the expression of costimulatory B7 molecules renders tumors invisible to the immune system (abstract). Zang discloses that B7-1 is a ligand for CD28 and CTLA-4, and discloses that CD28 engagement by B7-1 could enhance T cell proliferation and IL-2 production; and that anti-CD28 antibody could provide the costimulatory signal required to block T cell anergy induction (page 5271, col. 2). Zang teaches that the specific blockade of CTLA-4 signals is a very attractive approach for tumor immunotherapy and that administration of antibodies that block CTLA-4 interactions with B7-1 and B7-2 resulted in the rejection of colon carcinoma and fibrosarcoma, including preestablished tumors, providing a long-lasting immunity to a secondary exposure to tumor cells in the absence of additional treatment (reading on tumor vaccine) (Figure 1B and page 5273, col. 1, para. 2). Zang concludes by suggesting that blockade of the CTLA-4 check point has shown clinical benefit for patients with cancer, including long-term durable complete responses, and assuring this form of therapy will offer avenues for augmenting immune responses in the treatment of cancer with combination therapies (conclusion – para. bridging pages 5277-5278). Zang further teaches that both B7x and B7-H3 inhibit T cell function, therefore, B7x and B7-H3–positive tumor cells could have an advantage over the negative tumor cells by down-regulating T cell–mediated antitumor immunity. Consequently, the blockade of tumor-associated B7-H3 and B7x could offer a new therapeutic opportunity for the enhancement of antitumor immunity (page 5277, col. 1, last para.).
Therefore, it would have been prima facie obvious to one of ordinary skill prior to the effective filing date of the instant application to administer Walsh and Gee, immune-DASH and COX-2 inhibitor combination as part of a method for treating cancer, and further administer checkpoint inhibitor (such as an inhibitor of CTLA-4) or a costimulatory molecule (such as a B7x or B7-H3 inhibitor), as recited in instant claims 16-18. One of ordinary skill would have been motivated to do so with a reasonable expectation of success in view of Walsh and Gee, who disclose a Val-boroPro and COX-2 inhibitor combination for the treatment of bladder cancer; further in view of Zang’s teachings that blockade of the CTLA-4 check point has shown clinical benefit for patients with cancer, including long-term durable complete responses, and their suggestion that this form of therapy will offer avenues for augmenting immune responses in the treatment of cancer with combination therapies. One would have been further motivated with a reasonable expectation of success, specifically for claim 17, in view of Zang’s teaching that the blockade of tumor-associated B7-H3 and B7x (with a costimulatory molecule) could offer a new therapeutic opportunity for the enhancement of antitumor immunity.
Applicant is reminded, “[i]t is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art. It is therefore obvious to provide a mixture of the claimed agents.
Response to Arguments
Specification
Amendments to the specification are acknowledged and have been entered. No new matter has been introduced.
Claims/ Claim Objections
Claim amendments are acknowledged and have been entered. No new matter has been introduced.
Applicant’s arguments, see page 8, filed 02/10/2026, with respect to objections to the claims have been fully considered and are persuasive. The objection of the claims has been withdrawn. However, upon further consideration, a new ground(s) of objection is made in view of claim amendments.
Claim Rejections - 35 USC § 112(a)
Applicant’s arguments, see page 8-9, filed 02/10/2026, with respect to 35 USC § 112(a) rejections have been fully considered and are persuasive. The 35 USC § 112(a) rejection has been withdrawn.
Claim Rejections - 35 USC § 112(b)
Applicant’s arguments, see page 8-9, filed 02/10/2026, with respect to 35 USC § 112(b) rejections have been fully considered and are persuasive. The 35 USC § 112(b) rejection of the claims has been withdrawn.
Claim Rejections - 35 USC § 102
Applicant’s arguments, see page 8-9, filed 02/10/2026, with respect to 35 USC § 102 rejections have been fully considered and are persuasive. The 35 USC § 102 rejection of the claims has been withdrawn.
Claim Rejections - 35 USC § 103
Applicant’s arguments, see page 9-10, filed 02/10/2026, with respect to 35 USC § 103 rejections have been fully considered and are persuasive. The 35 USC § 103 rejection of the claims has been withdrawn. However, upon further consideration, a new ground(s) of rejection is made in view of Walsh and Gee – see rejections presented herein, necessitated by claim amendments.
Double Patenting
The terminal disclaimer filed on 02/10/2026 disclaiming the terminal portion of any patent granted on this application which would extend beyond the expiration date of US Patent No. 11,559,537 B2; 11,957,657 B2; 11,583,516 B2; 11,096,024 B2; or 12,478,609 B2 (cited as Copending App. No. 18/405,593 in the non-final filed 11/10/2025) has been reviewed and is accepted. The terminal disclaimer has been recorded.
The non-statutory double patenting rejections of record have been withdrawn.
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 JACKSON J HERNANDEZ whose telephone number is (571)272-5382. The examiner can normally be reached Mon - Thurs 7:30 to 5.
Examiner interviews are available via telephone 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, Kortney L. Klinkel can be reached at (571) 270-5239. 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.
/JACKSON J HERNANDEZ/Examiner, Art Unit 1627
/SARAH PIHONAK/Primary Examiner, Art Unit 1627