Status of the Claims
Claims 21-39 are pending and examined herein.
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claim Interpretation
Claims 22 and 23 recite further limitations to the composition of claim 21. These further limitations include the order with which the binding element is associated with its nucleic acid tag and attached to the bead. However, as claim 21 is directed to a composition (a “product”), these constitute product-by-process claims. As stated in MPEP § 2113, “If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior art was made by a different process.” Therefore, the order in which these attachments occur does not further limit patentability outside of any structural consequences of said steps, and a product of the prior art merely needs to be reasonably attainable by the claimed process in order to meet the claim. As the result of the process recited in both claims 22 and 23 is the composition of claim 21, this demonstrates that art that reads on claim 21 also necessarily reads on the following two claims.
The claims recite the term “attached” with regards to the relationship between elements of a composition. The specification states that “the terms ‘attaching’, ‘joining’ and ‘linking’ are used herein interchangeably and refer to either covalent or non-covalent attachment”, which will be used as the limiting definition of the term “attached”. However, it is not specified whether “attached” encompasses direct and/or indirect attachments. Therefore, the broadest reasonable interpretation will be used, and “attached” will be interpreted to encompass both direct and indirect attachments.
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.
Chee et al. and Babu et al.
Claims 21-28, 30-31, 34, 36, and 38-39 are rejected under 35 U.S.C. 103 as being unpatentable over Chee et al. (US 2019/0145982; cited in IDS of 05/30/2024) in view of Babu et al. (J. of Microbiol. Meth. (2011), 86: 188-194).
Regarding claims 21-23 and 30-31, Chee discloses a composition (Fig. 2C, top; p. 2, ¶[0013-4]) comprising a bead (p. 25-26, ¶[0330], particularly p. 26, lines 9-23) attached to a plurality of different antibody molecules (p. 21, ¶[0302]: “plurality of macromolecules”) and nucleic acid tags (Fig. 2C, top: “Abcap”, “recording tag”), and a plurality of antigen molecules (p. 21, ¶[0302]: “plurality of binding agents”), wherein each is bound to an antibody molecule and attached to a nucleic acid coding tag (Fig. 2C, top: “coding tag”) that comprises a sequence with identifying information (p. 10, ¶[0257]: “The coding tag is comprised of an encoder sequence providing identifying information for the binding agent”). Chee does not disclose a binding element attached to the bead that is configured to bind an antibody constant region and not a variable region. However, Chee does state that “proteins, polypeptides, or peptides can be joined to the solid support, directly or indirectly, by any means known in the art” (p. 34, ¶[0419]).
Babu discloses a composition (Fig. 1C) comprising a bead (“Protein G magnetic bead”) comprising a plurality of binding elements (“G” = protein G) wherein each of the plurality of binding elements is configured to bind to an antibody constant region and not a variable region (p. 192, Discussion: “We employed protein G-coated magnetic beads that can specifically bind with the FC portion of the capture antibodies”). Babu also discloses antibody molecules (Fig. 1C: “Capture Ab”) and antigen molecules (“Ag (aflatoxin)”) attached to a nucleic acid coding tag (“Reporter DNA”). Babu further teaches that use of protein G-coated magnetic beads properly orients the antigen binding fragments of the antibodies for antigen recognition (p. 192-3, Discussion).
Therefore, it would have been obvious to one of ordinary skill in the art by the effective filing date to use the antibody-bead attachment strategy of Babu in the complex of Chee, based on the motivation to properly orient the antibody for antigen binding. Furthermore, there would have been a reasonable expectation of success in doing so as Babu uses a similar “sandwich” method as Chee, and Chee states that immobilization on the bead can be achieved by any method known in the art.
Regarding claims 24 and 26, Chee further discloses that the nucleic acid tag is a nucleic acid recording tag comprising a UMI (p. 36, ¶[0438]) and/or a barcode (p. 36, ¶[0439]), wherein the barcode identifies a sample of origin (p. 36, ¶[0442-3]).
Regarding claims 25 and 27, Chee discloses sample specific barcodes as above but does not explicitly disclose sample barcodes that identify the sample of origin of different antibody molecules. However, Chee discloses that antibodies are “of particular interest” and can be selected for analysis by the disclosed method (p. 33, ¶[0413]). Therefore, based on the disclosure of Chee, it would have been obvious to one of ordinary skill in the art to analyze antibodies by the method of Chee and Babu, and incorporating the sample barcodes of Chee to yield sample-specific barcodes that identify a sample origin of the plurality of different antibody molecules attached to the bead.
Regarding claim 28, Chee does not state the number of samples that comprise the plurality of different samples. However, Chee does teach that multiplexing using sample barcodes can simultaneously process “many” samples (p. 58-9, ¶[0599]). Furthermore, Fig. 2D depicts a 96-well plate being utilized to isolate and barcode separate samples. Therefore, one of ordinary skill in the art would recognize that Chee teaches multiplexing at least 96 samples, further supported by the disclosure of “many” multiplexed samples.
Regarding claim 34, Chee further discloses that the antigen (“binding agent”) can be a peptide (p. 22, ¶[0312]; p. 39, ¶[0460])) and teaches that peptides are typically less than 20-30 amino acids (p. 22, ¶[0309]).
Regarding claim 36, Chee discloses that the coding tag hybridizes to the nucleic acid tag (Fig. 2C).
Regarding claim 38, Chee further discloses that the bead is “a polystyrene bead, a polymer bead, an agarose bead, an acrylamide bead, a solid core bead, a porous bead, a paramagnetic bead, a glass bead, or a controlled pore bead” (p. 33, ¶[0416]).
Regarding claim 39, Chee teaches a method of contacting a sample with the composition as described above, and allowing transfer of identifying information between the nucleic acid coding tags attached to the antigens and the nucleic acid tags of the bead, generating extended nucleic acid coding tags via primer extension (Fig. 2C, top; p. 10, ¶[0257], lines 19-21).
Chee et al., Babu et al., and Millipore Sigma
Claim 29 is rejected under 35 U.S.C. 103 as being unpatentable over Chee et al. in view of Babu et al., as evidenced by Millipore Sigma (“PureProteomeTM Protein A and Protein G Magnetic Beads” User Guide). Babu discloses that the Protein G beads were PureProteomeTM beads obtained from Millipore (p. 189, 2.3. Magnetic beads). Millipore Sigma teaches that the binding element is covalently attached to the bead (p. 1, Introduction, 2nd ¶).
Chee et al., Babu et al., and Schroeder et al.
Claim 32 is rejected under 35 U.S.C. 103 as being unpatentable over Chee et al. in view of Babu et al., as applied to claims 21-28, 30-31, 34, 36, and 38-39 above, and further in view of Schroeder et al. (Methods Protoc. (2019), 2(2): 35). Babu does not disclose that the constant region of the antibody molecules is covalently cross-linked to the binding element. Schroeder discloses crosslinking of antibody FC regions to protein G and also teaches that crosslinking is helpful for increasing binding capacity and preventing loss of bound antibodies (Abstract). Therefore, it would have been obvious to one of ordinary skill in the art by the effective filing date to incorporate the crosslinked binding element and antibody FC region of Schroeder to the composition of Chee and Babu, based on the motivation provided by Schroeder. Furthermore, there would have been a reasonable expectation of success in integrating this element as Schroeder states that the method to do so is applicable to a large variety of sample types and purity (Abstract).
Chee et al., Babu et al., and Lassauniere et al.
Claim 35 is rejected under 35 U.S.C. 103 as being unpatentable over Chee et al. in view of Babu et al. as applied to 21-28, 30-31, 34, 36, and 38-39 above, and further in view of Lassauniere et al. (medRxiv (2020), doi: 10.1101/2020.04.09.20056325; cited in IDS of 05/30/2024). Neither Chee nor Babu teach the use of SARS-CoV-2 virus within the method. However, Babu does teach the use of antigens derived from a pathogenic organism (p. 188, Introduction, 1st ¶).
Lassauniere teaches that there is an urgent demand for SARS-CoV-2 immunoassays and validation of serological tests (Abstract). It would have been obvious to one of ordinary skill in the art to sue peptide sequences from a SARS-CoV-2 virus as Lassauniere provides the motivation that there is a pressing need for these types of assays. There would have been a reasonable expectation of success in doing so as SARS-CoV-2 antigens were known (p. 3, ELISA assays: “SARS-CoV-2 spike protein receptor binding domain”) and the method of Babu similarly involved pathogenic antigens.
Chee et al., Babu et al., and Naimuddin et al.
Claims 33 and 37 are rejected under 35 U.S.C. 103 as being unpatentable over Chee et al. in view of Babu et al., as applied to 21-28, 30-31, 34, 36, and 38-39 above, and further in view of Naimuddin et al. (ACS Comb. Sci (2016), 18: 117-129).
Regarding claim 37, neither Chee nor Babu disclose that the nucleic acid coding tag comprises a cDNA that encodes the antigen. However, Chee teaches that a binding agent (antigen) can be made synthetically, including by mRNA display (p. 40-1, ¶[0473]), and discusses the use of display technology with the disclosed composition (p. 41, ¶[0476, 8]).
Naimuddin discloses a nucleic acid coding tag attached to an antigen where the tag comprises a cDNA that encodes the antigen (Figure 4a). Additionally, Naimuddin discloses a composition of an antibody bound to the antigen and indirectly attached to a bead via a binding element (Figure 4a: Selection on IgG matrix). Furthermore, Naimuddin teaches that the antigen-cDNA complex has a more rapid and efficient production than antigens produced through other display methods (p. 125, Conclusions; Table 2), and that it also enables a higher diversity of libraries for analysis (p. 126, 1st ¶). Therefore, it would have been obvious to one of ordinary skill in the art by the effective filing date to incorporate the antigen-cDNA complex of Naimuddin to the bead-antibody-antigen complex of Chee and Babu based on the motivation to streamline the production of the tagged antigen and increase the diversity of the library provided by Naimuddin. There would have been a reasonable expectation of success in doing so as the bead-antibody-antigen composition of Naimuddin is similar to that of Chee and Babu, and Chee references the use of display technologies, including mRNA display, in concert with the disclosed composition.
Regarding claim 33, Naimuddin further discloses that the plurality of antigen molecules comprises four structurally different antigen molecules (p. 123-4, In Vitro Selection: PDO, BDA, 3F, and 6R14).
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 21-39 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3, 7-8, 10-12, 16, and 27-29 of U.S. Patent No. 12123878 in view of Babu, Millipore Sigma, Lassauniere, and Naimuddin. The claims of the reference patent disclose a bead-antibody-antigen composition where the antibodies and antigens each comprise nucleic acid tags that allow for the transfer of information via primer extension and/or ligation. The claims of the reference patent further disclose covalent attachment of the macromolecule to the bead through an intermediary “linker” and sample barcodes. Therefore, with the disclosures of all other prior art of record, the claims of the instant application are rendered obvious.
Claims 21-39 are similarly rejected over U.S. Patents No. 11513126 and 12129463.
Conclusion
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/ALEXANDRA OLSON/Examiner, Art Unit 1684
/JEREMY C FLINDERS/Primary Examiner, Art Unit 1684
