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 .
Election/Restrictions
Applicant’s election of the invention of Group I, claims 1-11, and the species of conjugate A1 in the reply filed on 06/02/2026 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Claim Status
The response of 06/02/2026 has been entered. Claims 1-20 are pending in this US patent application. Claims 12-20 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.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 06/03/2026.
Information Disclosure Statement
The information disclosure statement filed in this application on 01/10/2025 has been received and considered.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 1-6 and 10-11 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Wang et al., Chem. Sci. 12: 331-340 (2021; cited on the IDS filed 01/10/2025).
Wang teaches chemically self-assembled nanorings comprising Fn3 domains capable of binding to EGFR or EpCAM that are tethered to bivalent dihydrofolate reductase fusion proteins (see entire document, including page 332, left column, paragraphs 1-2; reads on claims 2-3 and 10-11; reads on parts A.i. and A.ii. of claim 1). A CVIA prenyltransferase substrate domain was appended to the fusion proteins and geranylgeranylated with a geranylgeranyl transferase (page 332, right column, paragraphs 2-3; reads on claims 4-5; reads on parts A.iii., B., and C. of claim 1). The Examiner notes that a geranylgeranyl group can be interpreted as a geranyl linker A (cf. claim 5 and part B. of claim 1) attached to a geranyl group, of which part can be interpreted as a linker B and part as a ‘detectable agent’ (cf. part C. of claim 1); the linker and ‘detectable agent’ are not limited in claim 1, and any portion of a molecule is ‘detectable’ by at least some method. Regarding claim 6, the geranyl group interpreted as a linker B may also be interpreted as comprising the Z and T groups of claim 6 as branched, unsaturated hydrocarbon chains having 2 carbon atoms with the W and Y groups absent, as falls within the scope of claim 6 (please note that “wherein W, Z, T, and Y are not simultaneously absent” as recited in claim 6 indicates only that all four of the groups are not all absent, not that more than one of the groups may not be absent as is listed as an option for each of W, Z, T, and Y).
Therefore, claims 1-6 and 10-11 are anticipated by Wang and are rejected under 35 U.S.C. 102(a)(1).
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.
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.
Claims 1-8 and 10-11 are rejected under 35 U.S.C. 103 as being unpatentable over Wang et al., Chem. Sci. 12: 331-340 (2021; cited on the IDS filed 01/10/2025), in view of Suazo et al., Chem. Rev. 121: 7178-7248 (2021), and Dennler et al., Bioconj. Chem. 25: 569-578 (2014).
As discussed above, claims 1-6 and 10-11 are anticipated by Wang. In addition, Wang teaches that antibody-derived ligands are widely used scaffolds for cell targeting but that their biophysical properties make them less than optimal for many fundamental and clinical applications. The Fn3-DHFR2-CVIA-prenyl constructs may be used as an alternative to antibodies in these ligands (page 332, left column, paragraph 2). However, Wang does not teach the linkers recited in instant claim 7.
Suazo teaches that the addition of consensus sequences for lipidation can be incorporated into other proteins to provide a new site for selective modification, a feature that has been exploited for a myriad of applications including the creation of protein-drug conjugates for therapeutic applications. Click chemistry has played a key role in exploiting protein lipid modifications for these applications (see entire document, including page 7179, left column, paragraph 1), including the synthesis of protein-drug conjugates in which a drug cargo is linked through click chemistry to a targeted protein scaffold via a prenyl tag for targeted drug delivery (page 7226, left column, paragraph 1).
Dennler teaches the modification of antibodies to install a biorthogonal functionality that could be exploited for site-specific modification with a drug (see entire document, including page 569, right column, paragraph 1, to page 570, left column, paragraph 1). The modified antibody was reacted with the click reagent DBCO-PEG4-vc-PAB-MMAE, which produces an antibody linked through the DBCO-PEG4-vc-PAB linker to the cytotoxic drug MMAE (page 570, left column, paragraph 4, to right column, paragraph 3; page 575, left column, paragraph 2, to right column, paragraph 1; cf. claim 7). The antibody successfully targeted the drug to the desired cancer cells, which were killed by the delivered MMAE toxin (page 575, right column, paragraph 6, to page 576, left column, paragraph 1; cf. claim 8).
While Wang does not teach the conjugation of a drug to the Fn3-DHFR2-CVIA-prenyl constructs, it would have been obvious to one of ordinary skill in the art to do so because Wang teaches that antibody-derived ligands are widely used scaffolds for cell targeting but that their biophysical properties make them less than optimal for many fundamental and clinical applications. According to Wang, the Fn3-DHFR2-CVIA-prenyl constructs may be used as an alternative to antibodies in these ligands. Suazo teaches the synthesis of protein-drug conjugates in which a drug cargo is linked through click chemistry to a targeted protein scaffold via a prenyl tag for targeted drug delivery, and Dennler teaches the use of the reagent DBCO-PEG4-vc-PAB-MMAE to modify a targeting protein with the cytotoxic drug MMAE and the use of the drug conjugate to specifically kill cancer cells. As such, one of ordinary skill in the art would have a reasonable expectation that modifying the Fn3-DHFR2-CVIA-prenyl constructs of Wang through click chemistry processes as taught by Suazo by using the DBCO-PEG4-vc-PAB-MMAE reagent of Dennler would successfully result in the production of a Fn3-DHFR2-CVIA-prenyl-MMAE construct that selectively delivers MMAE to the cells targeted by the Fn3 domain.
Therefore, claims 1-8 and 10-11 are rendered obvious by Wang in view of Suazo and Dennler and are rejected under 35 U.S.C. 103.
Claims 1-6 and 9-11 are rejected under 35 U.S.C. 103 as being unpatentable over Wang et al., Chem. Sci. 12: 331-340 (2021; cited on the IDS filed 01/10/2025), in view of Suazo et al., Chem. Rev. 121: 7178-7248 (2021), and Astakhova et al., Mol. Pharmaceutics 15: 2892-2899 (2018).
As discussed above, claims 1-6 and 10-11 are anticipated by Wang. In addition, Wang teaches that antibody-derived ligands are widely used scaffolds for cell targeting but that their biophysical properties make them less than optimal for many fundamental and clinical applications. The Fn3-DHFR2-CVIA-prenyl constructs may be used as an alternative to antibodies in these ligands (page 332, left column, paragraph 2). However, Wang does not teach the nucleic acid therapeutic agent recited in instant claim 9.
Suazo teaches that the addition of consensus sequences for lipidation can be incorporated into other proteins to provide a new site for selective modification, a feature that has been exploited for a myriad of applications including the creation of protein-drug conjugates for therapeutic applications. Click chemistry has played a key role in exploiting protein lipid modifications for these applications (see entire document, including page 7179, left column, paragraph 1), including the synthesis of protein-drug conjugates in which a drug cargo is linked through click chemistry to a targeted protein scaffold via a prenyl tag for targeted drug delivery (page 7226, left column, paragraph 1).
Astakhova teaches that enhancing the target specificity of an oligonucleotide-based therapeutic is a crucial component to advance these therapeutics (see entire document, including page 2892, left column, paragraph 2). The direct conjugation of cell receptor targeted proteins to therapeutic RNAs through click chemistry techniques could revolutionize oligonucleotide therapeutics (page 2893, left column, paragraph 1; cf. claim 9).
While Wang does not teach the conjugation of a drug to the Fn3-DHFR2-CVIA-prenyl constructs, it would have been obvious to one of ordinary skill in the art to do so because Wang teaches that antibody-derived ligands are widely used scaffolds for cell targeting but that their biophysical properties make them less than optimal for many fundamental and clinical applications. According to Wang, the Fn3-DHFR2-CVIA-prenyl constructs may be used as an alternative to antibodies in these ligands. Suazo teaches the synthesis of protein-drug conjugates in which a drug cargo is linked through click chemistry to a targeted protein scaffold via a prenyl tag for targeted drug delivery, and Astakhova suggests that oligonucleotide therapeutics may be directly conjugated to cell receptor targeted proteins using click chemistry, which could revolutionize oligonucleotide therapeutics. As such, one of ordinary skill in the art would have a reasonable expectation that modifying the Fn3-DHFR2-CVIA-prenyl constructs of Wang through click chemistry processes as taught by Suazo with the oligonucleotide therapeutics of Astakhova would successfully result in the production of a Fn3-DHFR2-CVIA-prenyl-oligonucleotide construct that selectively delivers the oligonucleotide therapeutic to the cells targeted by the Fn3 domain.
Therefore, claims 1-6 and 9-11 are rendered obvious by Wang in view of Suazo and Astakhova and are rejected under 35 U.S.C. 103.
The Supreme Court has acknowledged:
When a work is available in one field of endeavor, design incentives and other market forces can prompt variations of it, either in the same field or a different one. If a person of ordinary skill can implement a predictable variation…103 likely bars its patentability…if a technique has been used to improve one device, and a person of ordinary skill in the art would recognize that it would improve similar devices in the same way, using the technique is obvious unless its actual application is beyond that person’s skill. A court must ask whether the improvement is more than the predictable use of prior-art elements according to their established functions……the combination of familiar elements according to known methods is likely to be obvious when it does no more than yield predictable results (see KSR International Co. v. Teleflex Inc., 82 USPQ2d 1385 U.S. 2007) (emphasis added).
From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. 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.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Erin M. Bowers, whose telephone number is (571)272-2897. The examiner can normally be reached Monday-Friday, 7:30-5:00.
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/Erin M. Bowers/Primary Examiner, Art Unit 1653 08/13/2026
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