Notice of Pre-AIA or AIA Status
1. 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
2. Applicant’s election without traverse of Group I, claims 1, 3, 6, 8, 9, 11, 15, 16 and 20 in the reply filed on 25 March 2026 is acknowledged.
Claim Rejections - 35 USC § 112
3. 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.
4. Claim 20 is 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.
Claim 20 recites the limitation "the… composition, or formulation of claim 1" in lines 1 and 2. Claim 1 only recites a “molecular conjugate,” so there is insufficient antecedent basis for these limitations in the claim
Claim Rejections - 35 USC § 102
5. 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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
6. Claims 1, 2, and 9 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Chee et al (United States Patent Application No. US 20190145982, published 16 May 2019).
Regarding claim 1, Chee teaches a molecular conjugate comprising a peptide (i.e., a molecular structure of interest; FIG 5A), a recording tag linked to the molecular structure (i.e., a nucleic acid linked to the molecular structure; FIG 5A), and that the recording tag comprises a universal forward primer binding site, a barcode and an Sp sequencing that hybridizes to an *Sp sequence on a coding tag (i.e., a capture sequence; FIG 5). Chee teaches that the recording tag is “a nucleic acid molecule” ([0324]) and that nucleic acids possess backbones other than standard phosphodiester linkages, such as phosphorothioate analogs ([0331]).
Regarding claim 2, Chee teaches that nucleic acid molecules (i.e., the recording tag) are DNA ([0331]).
Regarding claim 9, Chee teaches that the molecule conjugated to the recording tag is a peptide (FIG 5, FIG 11A and [0041]).
7. Claims 1, 2, 3, 6, 8, 9, 11, 15 , and 16 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Walsh et al (Molecular tracking devices quantify antigen distribution and archiving in the lymph node, BioRxiv, published 19 August 2020).
Regarding claim 1, Walsh teaches a molecular conjugate comprising an antigen (i.e., a molecular structure of interest) linked to a DNA tag (i.e., a nucleic acid; abstract). Walsh teaches that the nucleic acid tag comprises PCR primer binding sites (i.e., an amplification primer binding sequence), a barcode, and a 10X Genomics Gel Bead Primer binding site (i.e., a capture site; pg. 5 ¶ 1 and pg. 15 ¶ 2). Walsh teaches that the oligonucleotide is contains phosphorothiotate modifications “throughout” (pg. 5 ¶ 1 and FIG 1A).
Regarding claim 2, Walsh teaches that the nucleic acid is DNA (abstract and pg. 5 ¶ 1).
Regarding claim 3, Walsh teaches that the nucleic acid is functionalized with trans-cyclooctene (TCO), the antigen is conjugated to methyltetrazine, and they are conjugated together through an inverse electron demand Diels-Alder (iEDDA) reaction (pg. 15 ¶ 3 and 4, pg. 16 ¶ 1 and 2). Walsh teaches that the nucleic acid is functionalized through a 5' amino modification (pg. 15 ¶ 3) and that the nucleic acid comprises a 3' biotin modification (pg. 15 ¶ 2).
Regarding claim 6, Walsh teaches that ovalbumin is an antigen (pg. 5 ¶ 1).
Regarding claim 8, Walsh teaches that mice are vaccinated with a formulation comprising the molecular conjugate of claim 1 (i.e., pg. 6 ¶ 2).
Regarding claims 9 and 11, Walsh teaches that the molecular structure of interest comprises ovalbumin (i.e., a protein; pg. 5 ¶ 1). Regarding claim 11, it is noted that this claim only limits embodiments of claim 9 wherein the molecular structure of interest is a viral peptide or protein, and not embodiments wherein the molecular structure of interest is a peptide or protein that is not a viral peptide or protein.
Regarding claims 15 and 16, Walsh teaches that mice are vaccinated through footpad injection, and any solution injected into an animal for vaccination is considered a “pharmaceutically acceptable carrier” for the vaccine components (pg. 17 ¶ 4). Further, a footpad injection is inherently a parenteral injection, and therefore the formulation is suitable for parenteral injection.
Claim Rejections - 35 USC § 103
8. 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.
9. 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.
10. Claims 1, 2, 6, 9, 11 and 20 are rejected under 35 U.S.C. 103 as being unpatentable over Setliff et al (United States Patent Application No. US 20220315982, effectively filed 04 September 2020) in view of Viaud et al (International Patent Application No. WO 2018141908, published 09 August 2018).
Regarding claim 1, Setliff teaches a molecular conjugate comprising an antigen (i.e., a molecular structure of interest) conjugated to a unique antigen barcode (FIG 1B) and that the barcode is a DNA barcode ([0020]). Setliff teaches that amplification primers interaction with the antigen barcode tag ([0068]), which inherently means that the antigen barcode comprises a nucleic acid amplification primer binding site. Setliff teaches that the antigen barcode comprise a capture sequence ([0056]).
Setliff does not teach that the nucleic acid comprises a phosphorothioate modification at every nucleic acid linkage.
However, Viaud teaches oligonucleotides comprises phosphorothioate modifications at every nucleic acid linkage (pg. 10 ¶ 4).
It would have been obvious to one having ordinary skill in the art to have modified the antigen barcode taught by Setliff to incorporate the phosphorothioate modifications taught by Viaud to arrive at the instantly claimed invention with a reasonable expectation of success. One having ordinary skill in the art would have been motivated to make this modification because Viaud teaches that phosphorothioate modifications are useful for increasing the stability of oligonucleotides (pg. 2 ¶ 1). In addition, one having ordinary skill in the art would have recognized that the known techniques in the cited references could have been combined with predictable results because the known techniques in the cited references predictably result in the synthesis and use of oligonucleotides and modified oligonucleotides.
Regarding claim 2, Setliff teaches that the nucleic acid is DNA (“DNA-barcoded antigen,” [0053]).
Regarding claims 6, 9 and 11, Setliff teaches that the molecular structure is an antigen ([0007]) peptide from influenza (“H1 A/New Caledonia/20/99,” i.e., a virus peptide; [0046]).
Regarding claim 20, the preamble of this claim recites a “kit.” The specification, however, does not define this term, and so it is being interpreted to encompass any collection of reagents that includes all of the elements of the claims. Any further interpretation of the word is considered an “intended use” and does not impart any further structural limitation of on the claimed subject matter. Setliff teaches the molecular conjugate of claim 1 together with primers ([0068]). While Setliff does not teach instructions, the courts have found that “the content of the printed matter will not distinguish the claimed product from the prior art (In re Ngai, 367 F.3d 1336, 1339, 70 USPQ2d 1862, 1864 (Fed. Cir. 2004)).” See MPEP 2112.01 III. Therefore, because the courts have stated that the inclusion of instructions with an old product is obvious, the instantly claimed instructions are anticipated by Setliff.
11. Claim 3 is rejected under 35 U.S.C. 103 as being unpatentable over Setliff et al (United States Patent Application No. US 20220315982, effectively filed 04 September 2020) in view of Viaud et al (International Patent Application No. WO 2018141908, published 09 August 2018) as applied to claim 1 above, and further in view of Stoeckius et al (United States Patent Application No. US 20180251825, published 06 September 2018).
Regarding claim 3, the molecular conjugate of claim 1 is discussed fully above and incorporated here. Setliff teaches linking the DNA barcode to an antigen (i.e., a peptide from influenza; [0046] and [0143]), but Setliff does not teach that they are conjugated through an inverse electron demand Diels-Alder (IEDDA) reaction.
However, Stoeckius teaches the conjugation of a DNA to an antibody (i.e., a protein) by functionalizing the antibody with methyltetrazine-PEG4-NHS and functionalizing a 5'-amine-labeled oligonucleotide with trans-cyclooctene-PEG4-NHS and mixing the two ([0488]). This reaction inherently proceeds through an IEDDA reaction.
It would have been obvious to one having ordinary skill in the art to have simply substituted the antigen conjugation method with taught by Setliff with the antibody conjugation method taught by Stoeckius to arrive at the instantly claimed structure with a reasonable expectation of success. The ordinary artisan would have recognized that the two conjugation methods were substitutable alternatives because both methods functionalize amines on the antigen or antibody and functionalize an amino labeled oligonucleotide to achieve the reactive intermediates (Setliff [0143] and Stoeckius [0488]).
12. Claims 8, 15 and 16 are rejected under 35 U.S.C. 103 as being unpatentable over Setliff et al (United States Patent Application No. US 20220315982, effectively filed 04 September 2020) in view of Viaud et al (International Patent Application No. WO 2018141908, published 09 August 2018) as applied to claim 1 above, and further in view of Tamburini et al (Antigen capture and archiving by lymphatic endothelial cells following vaccination or viral infection, Nature Communications, 5, 3989, published 06 June 2014).
Regarding claim 8, Setliff in view of Viaud teaches the molecular conjugate of claim 1 as discussed fully above and incorporated here. Neither Setliff nor Viaud teach that the molecular structure is a component in and/or an ingredient in a vaccine.
However, Tamburini teaches that antigens are ingredients in vaccines (abstract, pg. 3 column 1 ¶ 2, FIG 3).
It would have been obvious to one having ordinary skill in the art to have modified the molecular conjugate taught by Setliff to have incorporated it into a vaccination mixture as taught by Tamburini to arrive at the instantly claimed structure with a reasonable expectation of success. The ordinary artisan would have been motivated to make this modification because Setliff teaches tracking antigen interactions via a DNA barcode (abstract) and Tamburini specifically teaches that tracking antigen persistence in vivo is important for understanding future vaccination strategies (abstract). In addition, one having ordinary skill in the art would have recognized that the known techniques in the cited references could have been combined with predictable results because the known techniques in the cited references predictably result in studying antigen modification and interactions.
Regarding claims 15 and 16, Tamburini teaches that mice are vaccinated intraperitoneally with an antigen composition (FIG 3 and caption). Without further limitation to the claim, any formulation capable of injection into a mouse is considered to comprise a “pharmaceutically acceptable carrier.” In addition, that Tamburini teaches the formulation is injected intraperitoneally inherently means that the formulation is suitable for injection intraperitoneally.
13. Claim 20 is rejected under 35 U.S.C. 103 as being unpatentable over Walsh et al (Molecular tracking devices quantify antigen distribution and archiving in the lymph node, BioRxiv, published 19 August 2020) in view of Ahern (Biochemical, Reagent Kits Offer Scientists Good return on investment, published 22 December 1998).
Regarding claim 20, the preamble of this claim recites a “kit.” The specification, however, does not define this term, and so it is being interpreted to encompass any collection of reagents that includes all of the elements of the claims. Any further interpretation of the word is considered an “intended use” and does not impart any further structural limitation of on the claimed subject matter. Walsh teaches the molecular conjugate of claim 1 together with primers (pg. 17 ¶ 2).
Walsh does not teach instructions, however Ahern teaches biochemical kits and instructions for said kits (pg. 4 ¶ 2).
It would have been obvious to one having ordinary skill in the art to have modified the molecular conjugate and the primers taught by Walsh to be provided in a kit with instructions as taught by Ahern to arrive at the instantly claimed invention with a reasonable expectation of success, and the ordinary artisan would have done this because Ahern specifically teaches that kits are convenient, save time and money (pg. 4 ¶ 2 and pg. 3 ¶ 4). In addition, one having ordinary skill in the art would have recognized that the known techniques in the cited references could have been combined with predictable results because the known techniques in the cited references predictably relate to common biochemical reagents.
Additionally, while Walsh does not teach instructions the courts have found that “the content of the printed matter will not distinguish the claimed product from the prior art (In re Ngai, 367 F.3d 1336, 1339, 70 USPQ2d 1862, 1864 (Fed. Cir. 2004)).” See MPEP 2112.01 III. Therefore, because the courts have stated that the inclusion of instructions with an old product is obvious, the instantly claimed instructions are made obvious by Walsh.
14. Claim 20 is rejected under 35 U.S.C. 103 as being unpatentable over Chee et al (United States Patent Application No. US 20190145982, published 16 May 2019).
Regarding claim 20, the preamble of this claim recites a “kit.” The specification, however, does not define this term, and so it is being interpreted to encompass any collection of reagents that includes all of the elements of the claims. Any further interpretation of the word is considered an “intended use” and does not impart any further structural limitation of on the claimed subject matter. Chee teaches the molecular conjugate of claim 1 together with primers (“a three-primer PCR approach is used to amplify the recording tag associated with the peptide; [0269]). While Chee does not teach instructions, the courts have found that “the content of the printed matter will not distinguish the claimed product from the prior art (In re Ngai, 367 F.3d 1336, 1339, 70 USPQ2d 1862, 1864 (Fed. Cir. 2004)).” See MPEP 2112.01 III. Therefore, because the courts have stated that the inclusion of instructions with an old product is obvious, the instantly claimed instructions are made obvious by Chee.
Conclusion
15. No claims are allowed.
16. Any inquiry concerning this communication or earlier communications from the examiner should be directed to BRIAN ELLIS YOUNG whose telephone number is (703)756-5397. The examiner can normally be reached M-T 0800 - 1630.
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/BRIAN ELLIS YOUNG/Examiner, Art Unit 1684
/JULIET C SWITZER/Primary Examiner, Art Unit 1682
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