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 .
Applicant’s amendments, filed 8/12/2026, is acknowledged.
Claims 2, 4, 5, 7-14, 16, 18, 19, 23, 26-32, 34, 36, and 38-49 are cancelled.
Claims 1, 3, 6, 15, 17, 20-22, 24, 25, 33, 35, 37, and 50-58 are currently pending and are under examination.
Claims 1 and 33 are independent claims.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 8/12/2026 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner in its entirety.
Applicant’s remarks, filed 2/09/2026, have obviated the previous 112(b) rejections by providing clarity to the terms used in claims 24 and 55 (Remarks pg. 6-8): “…Claims 24 and 55 specify that the collagen binding domain is from decorin or von Willebrand factor (VWF). Domains from vWF and decorin that can bind collagen are known in the art, such as described in [0070]-[0077] of the Specification as filed. Furthermore, the structure of the vWF collagen binding domain was already known at time of filing of the instant application, and so was how the structure relates to its binding properties. With such knowledge, a POSITA would have been well-guided to avoid changes to the functional core. For instance, the structure of the vWF collagen binding domain and the decorin collagen binding domain is described in many publications, including Romijn et al., Mapping the collagen- binding site in the von Willebrand factor-A3 domain. JBiol Chem. 2003 Apr 25;278(17):15035-9 (submitted in an IDS herewith) and Svensson et al., Decorin-binding sites for collagen type I are mainly located in leucine-rich repeats 4-5. J Biol Chem. 1995 Sep 1;270(35):20712-6 (submitted in an IDS herewith), respectively, which would allow a skilled artisan to select amino acids for modification while retaining desired function. In terms of structure-function relationship, mutagenesis and antibody-blocking studies have demonstrated that the front face of the A3 domain of vWF is responsible for collagen binding (which a skilled artisan could avoid), whereas the top and bottom faces do not contribute significantly (which a skilled artisan could modify). Mapping of 22 solvent-exposed residues on the front and bottom faces of A3 identified a discrete set of residues that are essential for collagen binding (which a skilled artisan could avoid). In particular, Asp979, Ser1020, and His1023 are critical (which a skilled artisan could avoid): alanine substitution at these positions nearly abolishes collagen binding in both solid-phase and surface plasmon resonance assays. The physicochemical properties of this region reveal a mixed surface containing hydrophobic patches adjacent to small negatively charged areas, consistent with recognition of collagen sequences enriched in hydrophobic and positively charged residues. Importantly, mutations at these critical positions do not globally disrupt folding, as evidenced by preserved binding to conformation-sensitive antibodies and normal multimerization of vWF, indicating that their effects are specific to ligand interaction rather than structural collapse. A second group of residues contributes to the collagen binding affinity of the vWF domain but is not strictly essential. Substitutions at I1e975, Thr977, Val997, and Glul001 result in approximately 5-10-fold reductions in binding affinity but retain near-normal maximal binding capacity. These residues are located in the upper half of the front face and appear to stabilize or fine-tune the interaction rather than form indispensable contact points. Their mutability suggests some flexibility in engineering the A3 surface without completely abolishing collagen binding.”
In view of the amendments and remarks filed on 12/04/2025, the following rejections remain.
Claim Objections
Claim 58 is objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Claim 58 recites allowable subject matter due to reciting the specific IL12/IL12R peptide combination that, when linked via the linker sequences recited in instant claim 33, demonstrate superior unexpected results (Remarks filed 2/09/2026 pg. 10-11, Office Action mailed on 3/13/2026).
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 1, 3, 6, 15, 17, 21, 25, 33, 35, 37, 50-53, and 56-57 are rejected under 35 U.S.C. 103 as being unpatentable over Winston et al. (U.S. PGPub 20190367576, in Office Action mailed on 3/13/2026) in view of Deming et al. (U.S. PGPub 20160186150, in Office Action mailed on 3/13/2026) and Bianchini et al. (Oncol Rep. 2006 Mar;15(3):709-14. PMID: 16465434, in Office Action mailed 3/13/2026), as evidenced by de Vries et al. (Am J Pathol. 1994 Jan;144(1):70-81. PMID: 8291613) and Moro et al. (Eur J Cell Biol. 2014 Jan-Feb;93(1-2):23-9. doi: 10.1016/j.ejcb.2014.01.002). This new grounds of rejection is necessitated by Applicant’s amendments.
The claims are rejected for the same reasons discussed in the Office Action mailed on 3/13/2026. The claims have not been amended. Regarding newly added claim 57, Winston et al. teaches the IL-12 comprises the p35 and p40 subunits (claim 17), and the IL-12R blocking moiety comprises IL-12Rß1 (¶[0091]), meeting the claim limitations.
Applicant’s arguments and remarks, filed on 8/12/2026 have been fully considered, but have been found to be not convincing.
Applicant argues: i) A prima facie case of obviousness has not been established; ii) The Office relies on improper use of hindsight; and iii) The claims are not obvious due to unexpected results.
i) Applicant argues prima facie case of obviousness has not been established due to a lack of expectation for success. Applicant argues (Remarks pg. 9): “…The Office relies on Bianchini for the proposition that MMP-2, MMP-9, and uPA are expressed in melanoma tumors, and on that basis concludes that a skilled artisan would have been motivated to incorporate cleavage sites for all three enzymes with a reasonable expectation of success. However, the Office selectively cites only the introductory background of Bianchini while disregarding the paper's own experimental data, which directly undermine any such expectation. Bianchini itself states "RT-PCR analysis and zymography revealed that melanoma cells, grown in standard conditions, do not express MMP-2 and MMP-9, a behavior which also characterized melanoma cells treated with IFNy"… MMP-9 was only induced under specific exogenous cytokine co-stimulation conditions (Figure 2 of Bianchini). A POSITA reading Bianchini in its entirety would thus understand that neither MMP-2 nor MMP-9 is constitutively expressed in melanoma, and that any MMP-9 activity is entirely contingent on the presence of specific cytokines”
This has been found to be not convincing. Bianchini et al. teaches melanoma expressed the MMP and uPA enzymes (Introduction): “…we focused our attention on matrix metalloproteinases 2 and 9 (MMP-2, MMP-9) and urokinase-type plasminogen activator (uPA) and its receptor (uPAR). Both systems of proteases are markers of melanoma progression. Indeed, uPA/uPAR and MMP are expressed in advanced stages of primary and metastatic melanoma lesions…”
Additionally, the prior arts of de Vries et al. and Moro et al. are provided as evidentiary references to demonstrate that MMP-2, MMP-9, and uPA were already known to be expressed in melanoma.
de Vries et al. teaches that uPA is expressed in metastatic melanoma (Results, Discussion): “…u-PA protein, mRNA, and activity were observed only in advanced primary melanomas and in melanoma metastases…[w]e located u-PA mainly to stromal cells, with a minority of u-PA-positive tumor cells at the invasive front.” Moro et al. additionally teaches MMP-2 and MMP-9 are expressing in melanoma tissue (Fig. 1, pg. 25): “…MMP-2 and MMP-9, also known as gelatinases A and B, were detected by immunohistochemical stainings in stroma and melanoma cells. Using in situ enzymatic assays, proteolytic activity of MMP-2 and MMP-9 was predominantly localised in peritumoural areas…” Thus, in contrast to Applicant’s assortations it was known in the art that melanoma, especially advanced primary or metastatic melanoma, expressed these enzymes.
ii) Applicant further argues (Remarks pg. 10-11): “…cited art discloses a vast combinatorial space of candidate cleavage sites for each of these proteases, and the only apparent basis for arriving at the specific combination of sequences recited in the claims is impermissible hindsight reconstruction using the claims themselves as a roadmap… the Office has failed to identify a principle, experimental result, or rationale taught or suggested in any of the cited references that would direct a POSITA to select precisely the three sequences as claimed from among this enormous field of candidates. The Office's analysis, reduced to its essence, amounts to an observation that the claimed sequences are among the many sequences that could have been selected for these three proteases. However, that is not a motivation to select them specifically…”
This has been found to be not convincing. In response to applicant's argument that the examiner's conclusion of obviousness is based upon improper hindsight reasoning, it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. In re McLaughlin , 443 F.2d 1392, 170 USPQ 209 (CCPA 1971). See MPEP 2145.
Appellant’s assertion that it is only with improper hindsight that the Examiner can combine Winston et al. in view of Deming et al. and Bianchini et al. to arrive at the instant invention, is misplaced; as the combination of references takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from Applicant's disclosure; thus, such a reconstruction is proper.
Additionally, although picking and choosing is not permissible in the context of an anticipatory rejection – the instant rejection is based on the grounds of obviousness. As explained in Arkley, picking and choosing may be entirely proper in the making of a 103 obviousness rejection, where the applicant must be afforded an opportunity to rebut with objective evidence any inference of obviousness which may arise from the similarity of the subject matter which he claims to the prior art, but it has no place in the making of a 102, anticipation rejection.
In re Arkley, 455 F.2d 586, 587-588 (CCPA 1972). Although both Brandle and Herold disclose multiple compositions and multiple disease targets, as explained by the Examiner the list of compositions and disease targets is small. Specifically, the Examiner finds that Brandle teaches "just 3 diseases [that] are specifically recited in the claims, [and] 2 of the 3 being the diseases of the instant claims" (Final Act. 3).
iii) Applicant argues unexpected results of the instantly claimed invention (Remarks pg. 12-13):
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This has been found to be not convincing. In contrast to assertations that increased pSTAT4 levels (though not significantly greater) translate to greater conjugate potency in the claimed methods of treating melanoma, Mansurov et al. teaches that the two linkers L4 and L6 do not significantly differ in potency in treating melanoma (Extended Fig. 1). Therefore, this change in pSTAT4 levels in an in vitro experiment do not measurably translate to the same increases in potency as Applicant asserts, and are not considered sufficient results to demonstrate unexpectedly superior changes in drug potency.
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
Claims 20, 22, 24, 54, and 55 are rejected under 35 U.S.C. 103 as being unpatentable over Winston et al. (supra) in view of Deming et al. (supra) and Bianchini et al. (supra), as evidenced by de Vries et al. (supra) and Moro et al. (supra) as applied to claims 1, 3, 6, 15, 17, 21, 25, 33, 35, 37, 50-53, and 56-57 above, and further in view of Frey et al. (Exp Dermatol. 2011 Aug;20(8):685-8. doi: 10.1111/j.1600-0625.2011.01314.x. Epub 2011 Jun 7, in Office Action mailed on 3/13/2026). This new grounds of rejection is necessitated by Applicant’s amendments.
The claims are rejected for the same reasons discussed in the Office Action mailed on 3/13/2026. Applicant’s arguments, filed on 8/12/2026 have been fully considered, but have been found to be not convincing.
Applicant argues that for the same reasons discussed for the 35 U.S.C. § 103 rejection supra, the rejection should be withdrawn. However, this was found to be not convincing for the reasons discussed supra.
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of 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.
Claims 1, 3, 6, 15, 17, 20-22, 24, 25, 33, 35, 37, and 50-57 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 9, 12, 17, 29, 34, 36, 39, 40, 45, 54, and 59-62 of copending Application No. 18/559,180 (herein App ‘180, in Office Action mailed on 3/13/2026, supra) in view of Winston et al. (U.S. PGPub 20190367576, in Office Action mailed on 3/13/2026, supra), Deming et al. (U.S. PGPub 20160186150, in Office Action mailed on 3/13/2026), and Bianchini et al. (Oncol Rep. 2006 Mar;15(3):709-14. PMID: 16465434, supra), as evidenced by de Vries et al. (Am J Pathol. 1994 Jan;144(1):70-81. PMID: 8291613, supra) and Moro et al. (Eur J Cell Biol. 2014 Jan-Feb;93(1-2):23-9. doi: 10.1016/j.ejcb.2014.01.002, supra). This new grounds of rejection is necessitated by Applicant’s amendments.
The claims are rejected for the same reasons discussed in the Office Action mailed on 3/13/2026. The claims have not been amended. Regarding newly added claim 57, App ‘180 claims IL-12 comprises the p35 and p40 subunits (i.e., the limitations of instant claims 3 and 50; App ‘180 claim 9), and the IL-12R comprises IL12β1 (i.e., the limitations of instant claims 6 and 51; App ‘180 claim 12), meeting the claim limitations.
Applicant’s arguments, filed on 8/12/2026 have been fully considered, but have been found to be not convincing.
Applicant argues that for the same reasons discussed for the 35 U.S.C. § 103 rejection supra, the rejection should be withdrawn. However, this was found to be not convincing for the reasons discussed supra.
Conclusion
No claim is allowed.
Claim 58 is objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
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 ALEC JON PETERS whose telephone number is (703)756-5794. The examiner can normally be reached Monday-Friday 8:30am - 6:00pm EST.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Misook Yu can be reached at (571) 272-0839. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/ALEC JON PETERS/Examiner, Art Unit 1641
/MISOOK YU/Supervisory Patent Examiner, Art Unit 1641
