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 .
Status of the Application
The Response filed June 11, 2026 is acknowledged.
Claims 1-15 were pending. Claims 1-3, 5-15 and new claim 16 are being examined on the merits. Claim 4 is canceled.
Response to Arguments
Applicant’s arguments filed June 11, 2026 have been fully considered.
The following objections and rejections are WITHDRAWN in view of Applicant’s arguments and the amendments to the specification and claims:
Objection to the Specification – missing sequence identifiers
Objections to claims 1, 6-7, 9-10 and 12-13
Rejection of claims 1-5, 7-8 and 13-15 under 35 USC § 112(b), indefiniteness
Rejection of claims 14-15 under 35 USC § 112(d)
The following rejections ae MODIFIED in view of the instant claim amendments:
Rejection of claims 1-5 and 14-15 under 35 USC § 101
Prior art rejections
Response to arguments regarding 35 USC § 101 rejections
The subject matter eligibility rejections are modified in view of the instant claim amendments. However, to the extent that Applicant’s arguments are relevant to the modified rejections below, the Examiner notes the following.
Applicant argues that the rejections should be withdrawn because, while some amphiphiles are products of nature, other amphiphiles are synthetic (Remarks, p. 10).
The Examiner disagrees. While it is true that some amphiphiles are synthetic, the instant claims are not limited to amphiphiles obtained from a particular source (e.g., they are not limited to synthetic amphiphiles). Thus, the instant claims encompass embodiments where the amphiphiles are naturally occurring (i.e., products of nature) and amphiphiles that are synthetically produced. However, even the embodiments directed to synthetically produced amphiphiles are ineligible if they are structurally and functionally identical to naturally occurring molecules. See MPEP 2106.04(b). Further, even if the instant claims comprise amphiphile embodiments that are not naturally occurring molecules and are not structurally and functionally identical to naturally occurring molecules, those embodiments do not negate the fact the broadest reasonable interpretation of the claims comprise either naturally occurring or structurally/functionally identical products. See MPEP 2106.04(b)(II).
Applicant argues that the rejections should be withdrawn at Step 2B of the analysis because “while the additional elements themselves may be known in the art, the use of these elements along with triterpene glycoside forms the inventive basis of the claims at issue” (Remarks, p. 11).
The Examiner disagrees. MPEP 2106.05 states “[a]n inventive concept ‘cannot be furnished by the unpatentable [judicial exception] itself … [i]nstead, an ‘inventive concept’ is furnished by an element or combination of elements that is recited in the claim in addition to (beyond) the judicial exception”. Thus, since the triterpene glycoside is the judicial exception, it is irrelevant to the analysis at Step 2B.
These arguments are not persuasive. The rejections are modified in view of the instant claim amendments.
Response to arguments regarding prior art rejections
The prior art rejections are modified in view of the instant claim amendments. However, to the extent that Applicant’s arguments are relevant to the modified rejections below, the Examiner notes the following.
Applicant argues that Raybuck can be distinguished from claims 1-6, 12 and 14-15 because the Raybuck composition can be used in a method that is different from the claimed method, and specifically that the claimed invention allows lysis and DNA synthesis to take place in the same reaction mixture (Remarks, p. 13).
The Examiner disagrees as to the product claims. The intended use of a product claim is not relevant to patentability, unless the intended use results in a structural difference in the claimed product. MPEP 2111.02 (II). Further, it is noted that, e.g., claim 1 only requires that the cell lysis reagents and the DNA synthesis reagents are comprised in the same mixture. It does not explicitly or implicitly require that cell lysis and DNA synthesis actually occur in the same reaction mixture or at the same time.
Similarly, Applicant argues that “claims 1 and 14 now read on the fact that both … the lysis and DNA synthesis take place in one single reaction mixture” (Remarks, pp. 16-17).
The Examiner disagrees. Again, claims 1 and 14 are product claims. No method steps are taking place in a product claim, and the intended use of the product claim does not have patentable weight, for the reasons noted above.
Applicant argues that claims 6, 8 and 10-13 are distinguishable from Weitz because Weitz “does not teach that the lysis and DNA synthesis could be conducted in a single reaction mixture” (Remarks, p. 15).
The Examiner disagrees. Weitz teaches this limitation, at least, at Figs. 2A and 27, as noted below in the rejection.
Applicant argues that the rejection of claims 7 and 9 should be withdrawn because neither Weitz nor Raybuck teaches that lysis and DNA synthesis take place in a single reaction volume (Remarks, p. 16).
The Examiner disagrees for the reasons noted above.
These arguments are not persuasive. The rejections are modified in view of the instant claim amendments.
Claim Objections
Claim 6 is objected to because of the following informalities:
In claim 6, the limitation “reagents lyse” in l. 5 should be “reagents to lyse”, and the
limitation “reagents reverse transcribe” in l. 8 should be “reagents to reverse transcribe”.
Appropriate correction is required.
Claim Rejections - 35 USC § 112
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.
Claims 1-3, 5 and 15-16 are 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.
Regarding claim 1, a broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, claim 1 recites the broad recitation “a first amphiphile that binds to fatty acids, phospholipids, glycolipids and/or sterols”, and the claim also recites “the first amphiphile is triterpene glycoside” which is the narrower statement of the range/limitation. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims. Since the ordinary artisan would not be able to determine the metes and bounds of the claim,
Claims 2-3, 5 and 15-16 depend directly or indirectly from claim 1, and consequently
incorporate the indefiniteness issue of claim 1.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 1-3, 5 and 14-16 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception without significantly more.
Eligibility is considered in light of MPEP 2106 III, which incorporates the 2019 Revised Patent Subject Matter Eligibility Guidance (2019 PEG) published on January 17, 2019 (84 Fed. Reg. 50) and clarified in the October 2019 Update.
As can be seen in the MPEP 2106 III Figure, eligibility analysis requires one to address the following questions: (i) Step 1 – Is the claim directed to one of the four statutory categories (i.e., process, machine, manufacture or composition of matter); (ii) Step 2A – Is the claim directed to a judicial exception (i.e., a natural phenomenon, law of nature or abstract idea); and (iii) Step 2B – does the claim recite additional elements that amount to significantly more than the judicial exception. In addition, as can be seen in the MPEP 2106.04 II Figure, Step 2A is a two-prong inquiry, with Prong One asking whether the claims recite a judicial exception (i.e., an abstract idea, natural phenomenon or law of nature) and Prong Two asking whether the claims recite additional elements that integrate the judicial exception into a practical application.
In this case, as to Step 1, claims 1-3, 5 and 14-16 are directed to one of the four statutory categories since they are drawn to a composition of matter.
The analysis cannot be streamlined, so the claims are considered with respect to Step 2A.
With respect to Prong One of Step 2A, claims 1-3, 5 and 14-16 recite a judicial exception. Specifically, at least some amphiphiles are products of nature (i.e., a natural phenomenon). For example, saponin is derived from plants (Raybuck (WO 98/26284 A1): p. 4, l. 18). In addition, DNA synthesis reagents, e.g., polymerases (Taq polymerase, Weitz: para. 120, is isolated from Thermus aquaticus), are also products of nature. Further, while it is not clear that a mixture of amphiphiles and DNA synthesis reagents exist in nature, there is no evidence that such a combination would have markedly differently characteristics as compared to the individual components of the mixture.
With respect to Prong Two of Step 2A, the claims do not recite additional elements that integrate the judicial exceptions into a practical application for the following reason. In particular, claims 1-3, 5 and 16 do not require any components other than the judicial exceptions. In addition, claims 14-15 do not recite additional elements that integrate the judicial exceptions into a practical application because the elements in the claim other than the judicial exceptions (i.e., additional reagents, the composition assembled into a kit) constitute insignificant extra-solution activity as described in the 2019 PEG and MPEP 2106.05(g).
Thus, the answer to step 2A is “Yes, the claims are directed to a judicial exception,” and the analysis moves to Step 2B, which asks if the additional elements in the claim amount to significantly more than the judicial exception.
In this case, claims 1-3, 5 and 14-16 do not include additional elements that are sufficient to amount to significantly more than the judicial exception because no additional elements are recited in claims 1-3, 5 and 16, and only routine and conventional elements are recited in combination with the judicial exceptions in claims 14-15. Assembling reagents into kits was performed routinely prior to the effective filing date of the claimed invention (e.g., see Raybuck below, cited in conjunction with the prior art rejections), as was including additional reagents, such as non-ionic detergents (Raybuck: p. 10, ll. 15-26; claims 5-7). Therefore, the additional elements in claims 14-15 are not non-routine or unconventional.
In view of the foregoing, claims 1-3, 5 and 14-16 are rejected under 35 U.S.C. 101 as being drawn to a judicial exception without significantly more.
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 6, 8 and 10-13 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Weitz1 (US Patent App. Pub. No. 2018/0071705 A1).
Regarding independent claim 6 and dependent claims 8 and 12-13, Weitz teaches a
method of cell lysis and DNA synthesis, where the method comprises the steps: adding cells, cell lysis reagents and DNA synthesis reagents to a single reaction mixture, allowing the cell lysis reagents to lyse the cells to release the desired component from the cells, wherein the desired component is nucleic acid; and allowing the DNA synthesis reagents to reverse transcribe, synthesize, replicate and/or amplify the nucleic acid in the single reaction mixture, optionally using PCR, quantitative PCR, or RT-PCR. Weitz additionally teaches that the reaction mixture is loaded into a microreactor (a microwell or a water-in-oil droplet) with a volume of 50 pL to 10 nL (Figs. 1, 2A, 27; paras. 57, 59-63, 70, 112; Example 1).
Regarding dependent claims 10-11, Weitz additionally teaches encapsulating a plurality of cells and a plurality of DNA barcoding beads in a plurality of droplets together with the lysis reagents and reagents needed for reverse transcribing, synthesizing, replicating and/or amplifying the nucleic acid, wherein each bead of the plurality of beads comprises RT primers that include a molecular tag, and some droplets comprise cells and beads, and wherein: the plurality of droplets comprises cell lysis reagents, DNA synthesis reagents, RT reaction reagents, and no more than one cell and no more than one bead, and the molecular tag of RT primers on the bead in one droplet is distinguishable from the molecular tags of the RT primers on the beads in the other droplets; (ii) lysing the cells; and (iii) converting RNA into cDNA by reverse transcriptase using molecular tags and RT primers (Figs. 1, 2A, 27; paras. 57, 59-63, 69-72, 76, 112; Example 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.
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 1-3, 5 and 14-16 are rejected under 35 U.S.C. 103 as being unpatentable over Weitz (US Patent App. Pub. No. 2018/0071705 A1) in view of Raybuck2 (WO 98/26284 A1).
Regarding independent claim 1 and dependent claims 2-3, 5 and 16, Weitz teaches …
A reagent composition for cell lysis and DNA synthesis in a single reaction mixture,
comprising: a cell lysis reagent and a DNA synthesis reagent in the same reaction volume (Figs. 1, 2A, 27; paras. 57, 59-63, 70, 112; Example 1).
In addition, Raybuck teaches a cells lysis reagent comprising first amphiphile that binds to fatty acids, phospholipids, glycolipids, and/or sterols, optionally saponin; wherein the first amphiphile is triterpene glycoside, and wherein said triterpene glycoside amphiphile does not lower activity of the enzymatic reactions in the single reaction mixture needed to synthesize DNA by more than 10%, and/or does not lower the activity of reverse transcriptase for the synthesis of copy DNA by more than 10% (p. 10, ll. 15-26; claims 5-7). Raybuck further teaches that the cell lysis reagent comprises a second amphiphile that is non-ionic and belongs to the class of detergents consisting of octylphenoxypolyethoxy nonylphenols, specifically TRITON X100 (p. 10, ll. 15-26; claims 5-7). Raybuck also teaches that the concentration of the first amphiphile is in the range of 0.00001% to 10% (w/v), and optionally in the range of 0.001% to 1% (w/v) (p. 11, ll. 20-24; claims 5-7: 0.01-0.1 wt% saponin).
Regarding dependent claim 14, Weitz teaches …
A reagent composition for cell lysis and DNA synthesis, comprising: a cell lysis reagent
and a DNA synthesis reagent (Figs. 1, 2A, 27; paras. 57, 59-63, 70, 112; Example 1).
In addition, Raybuck teaches a cells lysis reagent comprising triterpene glycoside, and a non-ionic detergent, specifically TRITON X100 (p. 10, ll. 15-26; claims 5-7).
Both, Weitz (para. 295) and Raybuck (p. 10, ll. 15-26; claims 5-7; p. 14, ll. 12-15) teach that the composition is assembled into a kit.
Regarding the limitation “instructions for cell lysis and DNA synthesis in a single reaction mixture”, Weitz teaches various protocols using the reagent composition (e.g., para. 262), but doesn’t explicitly teach that the kit comprises those instructions. Nevertheless, these instructions do not distinguish the art. MPEP 2111.05(I)(B) states that “[t]o be given patentable weight, the printed matter and associated product must be in a functional relationship”, and then states …
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Thus, here, as with In re Ngai, the instructions for use do not have patentable weight. Stated differently, attaching new instructions to a known product does not make the known product patentable.
Regarding independent claim 15, Weitz and Raybuck teach the reagent composition of claim 1 (see citations above). Raybuck additionally teaches that the composition comprises a non-ionic detergent, specifically TRITON X100. Both, Weitz (para. 295) and Raybuck (p. 10, ll. 15-26; claims 5-7; p. 14, ll. 12-15) teach that the composition is assembled into a kit.
Prior to the effective filing date of the instant invention, it would have been prima facie
obvious to modify the Weitz method and corresponding product to incorporate the Raybuck cell lysis reagent. Weitz teaches the need for a cell lysis reagent that can be incorporated into a droplet comprising a cell, and teaches that various reagents are suitable for such a purpose, including those comprising various surfactants and detergents. Raybuck teaches a cell lysis reagent comprising surfactants and detergents that are suitable for cell lysis and which do not damage target nucleic acid. It would have been obvious for the ordinary artisan to try the Raybuck cell lysis reagent in the Weitz method to customize the Weitz method and corresponding product to detect the desired target nucleic acid through routine optimization. The ordinary artisan would have had an expectation of success as nucleic acid assay design and optimization is well-known in the art.
Claims 7 and 9 are rejected under 35 U.S.C. 103 as being unpatentable over Weitz (US Patent App. Pub. No. 2018/0071705 A1) as applied to claim 6 above, and further in view of Raybuck (WO 98/26284 A1).
Regarding dependent claim 7, Raybuck teaches that the cell lysis reagents comprise a
first amphiphile and/or the second, non-ionic amphiphile (p. 10, ll. 15-26; claims 5-7), and Weitz teaches that DNA synthesis reagents comprise reverse transcription (RT) reagents, and DNA synthesis reagents comprise PCR reagents (Figs. 1, 2A, 27; paras. 57, 59-63, 70, 112; Example 1).
Regarding dependent claim 9, Weitz teaches that the cell lysis and DNA synthesis in
single-cells comprises the steps:(i) adding cells, DNA barcodes, cell lysis reagents and DNA synthesis reagents in a microreactor; (ii) lysing the cells to release the desired component from the cells, wherein the desired component is nucleic acid; and (iii) reverse transcribing, synthesizing, replicating and/or amplifying the nucleic acid (Figs. 1, 2A, 27; paras. 57, 59-63, 69-72, 76, 112; Example 1), while Raybuck teaches that the cell lysis reagents comprise triterpene glycoside with or without a second, non-ionic amphiphile (p. 10, ll. 15-26; claims 5-7).
Prior to the effective filing date of the instant invention, it would have been prima facie
obvious to modify the Weitz method to incorporate the Raybuck cell lysis reagent. Weitz teaches the need for a cell lysis reagent that can be incorporated into a droplet comprising a cell, and teaches that various reagents are suitable for such a purpose, including those comprising various surfactants and detergents. Raybuck teaches a cell lysis reagent comprising surfactants and detergents that are suitable for cell lysis and which do not damage target nucleic acid. It would have been obvious for the ordinary artisan to try the Raybuck cell lysis reagent in the Weitz method to customize the Weitz method to detect the desired target nucleic acid through routine optimization. The ordinary artisan would have had an expectation of success as nucleic acid assay design and optimization is well-known in the art.
Conclusion
Claims 1-3 and 5-16 are being examined and are rejected. Claim 6 is objected to. No claims are allowed.
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 CAROLYN GREENE whose telephone number is (571)272-3240. The examiner can normally be reached M-Th 7:30-5:30 EST.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Gary Benzion can be reached at 571-272-0782. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/CAROLYN L GREENE/Primary Examiner, Art Unit 1681
1 Weitz was cited in the PTO-892 Notice of References Cited mailed March 11, 2026.
2 Raybuck was cited in the PTO-892 Notice of References Cited mailed March 11, 2026.
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