sDETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA . Applicant should note that the examiner assigned to this case has changed.
Election/Restrictions
Applicant’s species election requirement is incomplete, as a provisional election is required even when traversing the election requirement. See M.P.E.P. § 818.01(b). In this case, Applicant did not elect a single discrete and disclosed species of polymerization solution and gelation solution as required in the instant reply.
Nevertheless, without acquiescing to Applicant’s position in the instant remarks and solely to expedite prosecution, the species election for claims 8-11 is withdrawn.
Applicant’s species election of organ slices in the reply filed on 8/06/2025 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Claim 18 is withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 8/06/2025.
Claims 1-17, 29, and 20 are under consideration on the merits and to the extent they read on the elected species.
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 1-17, 19, and 20 are rejected under 35 U.S.C. 103 as being unpatentable over Sarkar et al. (US 2020/0271556; Reference A) in view of Chen et al. (Science (2015), 347(6221), 543-548 plus appended Supplemental Material; Reference U).
Sarkar teaches a termed iterative direct expansion microscopy (Abstract). Sarkar teaches a method of preparing a tissue sample for imaging a target biomolecule within the tissue sample with a targeting reagent, comprising: (a) treating the tissue sample with a chemical fixative; (b) treating the tissue sample with a first anchor for attaching the target biomolecule to a linear polymer to be synthesized subsequently; (c) treating the tissue sample with a polymerization solution to be polymerized to generate the linear polymer, wherein the polymerization solution comprises first monomers, which are monomers of the linear polymer (d) allowing the first monomers in the solution to polymerize and link to the target biomolecule via the first anchor, (f) incubating the tissue sample with a gelation solution to be polymerized to generate a swellable hydrogel, wherein the gelation solution comprises second monomers, which are monomers of the swellable hydrogel, and a cross-linker; and (g) allowing the swellable hydrogel to form, wherein the second component of the second anchor is incorporated into the swellable hydrogel via the second moiety of the second component of the second anchor, thereby embedding the tissue sample and the target biomolecule within the swellable hydrogel (Example 2; fixation at ¶0029; biomolecule anchoring agent at ¶0016-0018; first polymerization solution comprised of monomers having moieties which then polymerize (¶0007-0008, ¶0032-0033, and ¶0043; swellable hydrogel ¶0042-0043), reading in-part on claim 1.
Sarkar teaches the biomolecule anchoring agent (BAA) may comprise a protein-reactive chemical moiety and an anchor such as aryl azide (¶0038), reading on the azido-moiety of claim 2. Sarkar teaches a protein-reactive chemical group is a succinimidyl ester of 6-((acryloyl)amino) hexanoic acid (acryloyl-X, SE; abbreviated "AcX") wherein treatment with AcX modifies amines on proteins with an acrylamide functional group (¶0039), reading on that embodiment of the acryloyl moiety of claim 2. Sarkar teaches slicing brain tissue before treatment with any anchor compounds (¶0087), reading on claim 3. Sarkar teaches expanding the swellable hydrogel (Example 2 at ¶0086), reading on claim 4. Sarkar teaches further comprising treating the tissue sample embedded within the swellable hydrogel with a disruption buffer prior to expanding the swellable hydrogel (Example 2; i.e. the “disruption buffer” is the buffer contacted to sample during the swelling of the hydrogel), reading on claim 5. Sarkar teaches further treating the tissue with secondary antibodies and imaging the tissue (¶0088), reading on the embodiment of secondary antibodies for claim 6 and reading on claim 7. Sarkar teaches APS as an initiator and TEMED as an accelerator (¶0086), reading on claims 8 and 10 respectively. Sarkar teaches placing the tissue sample embedded within the swellable hydrogel in a chamber and incubating with a stabilizing gelation solution comprising monomers of a swellable stabilizing gel wherein the stabilization gelation solution comprises a APS as a species of chemical initiator or a bisacrylamide crosslinker, and incubating with an immobilization gelation solution comprising monomers of an immobilization gel wherein the stabilization gelation solution comprises a APS as a species of chemical initiator or a bisacrylamide crosslinker (¶0007-0008 and Examples 1 and 2, i.e. the 2nd swellable gel for the stabilizing and immobilizing gels), reading on claims 12-15. Sarkar teaches obtaining brain tissue from mice and slicing said tissue prior to imaging (¶0086-0088), reading on claims 16 and 17. Sarkar teaches transcardially perfusing the mice with fixative prior to removing and slicing the brain (¶0087), reading on claim 19. Sarkar teaches imaging two synaptic proteins, bassoon and PSD-95 (¶0088), reading on the embodiment of proteins for claim 20.
Regarding claim 1, Sarkar does not teach part of step (c) of claim 1, directed towards a first component of a second anchor having: (1) a first moiety for incorporating into the linear polymer, and (2) a second moiety for reacting with a second component of the second anchor Sarkar does not teach step (e) of claim 1, directed towards treating the tissue sample with the second component of the second anchor having a first moiety that is reactive with the second moiety of the first component of the second anchor for engaging the first component of the second anchor, and a second moiety for incorporating into a swellable hydrogel. Regarding claim 3, Sarkar is silent if the tissue sample is sliced before treatment with the second component of the second anchor. Regarding claim 9, Sarkar does not teach wherein the polymerization solution comprises an inhibitor to delay polymerization. Regarding claim 11, Sarkar does not teach wherein the gelation solution comprises an inhibitor to delay polymerization.
Chen teaches methods of expansion microscopy, wherein physically expanding the swellable polymer network in a (tissue) specimen results in physical magnification (Abstract). Chen teaches anchoring multiple labels and anchors attached to the polymer network, the anchor comprising a methacryloyl group covalently bound to an oligonucleotide and a chemical fluorophore such as to detect different labeled biomolecules in sliced brain tissue (Fig. 1 and 3), reading on step (e) of claim 1. Chen teaches adding the inhibitor 4-hydroxy-2,2,6,6-tetramethylpiperidin-1-oxyl (4-hydroxy-TEMPO) up to 0.01% (w/w) to inhibit gelation during diffusion of the monomer solution into the tissue sections (Supplementary Materials, subheading “In situ polymer synthesis”), reading on claims 9 and 11.
Regarding steps (c) and (e) claim 1, it would have been obvious to a person of ordinary skill in the art before the invention was filed to add the anchor comprising a methacryloyl group covalently bound to an oligonucleotide and a chemical fluorophore of Chen to the iterative direct expansion microscopy methods of Sarkar. A person of ordinary skill in the art would have had a reasonable expectation of success to do so because Sarkar and Chen are both directed towards methods of expansion microscopy and imaging of sliced brain tissue. The skilled artisan would have been motivated to do so because Chen teaches that the addition would be predictably advantageous to label and detect multiple biomolecules of interest in the sliced tissue (e.g. Fig. 3 of Chen).
Regarding claims 9 and 11, it would have been obvious to a person of ordinary skill in the art before the invention was filed to add polymerization inhibitor of Chen to the iterative direct expansion microscopy methods of Sarkar. A person of ordinary skill in the art would have had a reasonable expectation of success to do so because Sarkar and Chen are both directed towards methods of expansion microscopy and imaging of sliced brain tissue. The skilled artisan would have been motivated to do so because Chen teaches that the addition would be predictably advantageous to delay polymerization when the monomer solution is diffusing into the tissue section.
Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill before the invention was filed.
Conclusion
No claims are allowed. No claims are free of the art.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SEAN C BARRON whose telephone number is (571)270-5111. The examiner can normally be reached 7:30am-3:30pm EDT/EST (M-F).
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/Sean C. Barron/Primary Examiner, Art Unit 1653
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