Y 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 .
Claims 1-15 are pending and are being examined on the merits.
Information Disclosure Statement
The Information Disclosure Statement submitted July 10, 2023 has been considered.
Nucleotide and/or Amino Acid Sequence Disclosures
REQUIREMENTS FOR PATENT APPLICATIONS CONTAINING NUCLEOTIDE AND/OR AMINO ACID SEQUENCE DISCLOSURES
Items 1) and 2) provide general guidance related to requirements for sequence disclosures.
37 CFR 1.821(c) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.821(a) must contain a "Sequence Listing," as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.821 - 1.825. This "Sequence Listing" part of the disclosure may be submitted:
In accordance with 37 CFR 1.821(c)(1) via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter "Legal Framework") as an ASCII text file, together with an incorporation-by-reference of the material in the ASCII text file in a separate paragraph of the specification as required by 37 CFR 1.823(b)(1) identifying:
the name of the ASCII text file;
ii) the date of creation; and
iii) the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(1) on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation-by-reference of the material in the ASCII text file according to 37 CFR 1.52(e)(8) and 37 CFR 1.823(b)(1) in a separate paragraph of the specification identifying:
the name of the ASCII text file;
the date of creation; and
the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(2) via the USPTO patent electronic filing system as a PDF file (not recommended); or
In accordance with 37 CFR 1.821(c)(3) on physical sheets of paper (not recommended).
When a “Sequence Listing” has been submitted as a PDF file as in 1(c) above (37 CFR 1.821(c)(2)) or on physical sheets of paper as in 1(d) above (37 CFR 1.821(c)(3)), 37 CFR 1.821(e)(1) requires a computer readable form (CRF) of the “Sequence Listing” in accordance with the requirements of 37 CFR 1.824.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed via the USPTO patent electronic filing system as a PDF, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the PDF copy and the CRF copy (the ASCII text file copy) are identical.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed on paper or read-only optical disc, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the paper or read-only optical disc copy and the CRF are identical.
Specific deficiencies and the required response to this Office Action are as follows:
Specific deficiency – Nucleotide and/or amino acid sequences appearing in the specification are not identified by sequence identifiers in accordance with 37 CFR 1.821(d). Specifically, the sequences in Tables 2, 6-7 and 10-11 are missing sequence identifiers.
Required response – Applicant must provide:
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required sequence identifiers, consisting of:
A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
A copy of the amended specification without markings (clean version); and
A statement that the substitute specification contains no new matter.
Specific deficiency – Nucleotide and/or amino acid sequences appearing in the drawings are not identified by sequence identifiers in accordance with 37 CFR 1.821(d). Sequence identifiers for nucleotide and/or amino acid sequences must appear either in the drawings or in the Brief Description of the Drawings. Specifically, the sequences in Fig. 5 are missing sequence identifiers.
Required response – Applicant must provide:
Replacement and annotated drawings in accordance with 37 CFR 1.121(d) inserting the required sequence identifiers;
AND/OR
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required sequence identifiers into the Brief Description of the Drawings, consisting of:
A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
A copy of the amended specification without markings (clean version); and
A statement that the substitute specification contains no new matter.
Claim Objections
Claims 1, 6-7, 9-10 and 12-13 are objected to because of the following informalities:
In claim 1, “a” should be added in between “of” and “cell” in l. 1.
In claim 6, “comprising” in l. 1 should be “comprises”. In addition, the phrase “are lysed” should be removed from l. 3.
In claim 7, “comprising” in l. 1 should be “comprise”.
In claim 9, “comprising” in l. 2 should be “comprise”.
In claim 10, bullet point (i) is missing. In addition, in step 10(v), the phrase “at RT primers” should be “and RT primers”.
In claim 12, the phrase “polymerase chain reaction (PCR) is listed twice (once in l. 2 and
once in l. 4). One instance should be removed. The same informality appears in claim 13, and it should be corrected, as well.
Appropriate correction is required.
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 1-5 and 14-15 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 1-5 and 14-15 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 1-5 and 14-15 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).
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 1-5 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., 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 1-5 and 14-15 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 1-5, 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). Therefore, the additional elements in claims 14-15 are not non-routine or unconventional.
In view of the foregoing, claims 1-5 and 14-15 are rejected under 35 U.S.C. 101 as being drawn to a judicial exception without significantly more.
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 1-5, 7-8 and 13-15 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.
Indefiniteness rejections
Claim 1 recites the limitation “a first amphiphile that preferentially binds to [various
molecules]”, the meaning of which is unclear. Specifically, the term “preferentially” in claim is a relative term which renders the claim indefinite. The term “preferentially” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. Stated differently, what minimum degree of binding does the first amphiphile have to exhibit to be considered “preferentially” binding? Since the ordinary artisan would not be able to determine the metes and bounds of the claim, it is indefinite.
Claims 2-5 and 14 depend from claim 1, and consequently incorporate the indefiniteness issue of claim 1. Claim 15 is also being construed as depending indirectly from claim 1 (see below).
Claim 3 recites two parenthetical limitations – “(known as different types of Tergitol)” and “(known as different types of Brij)” – the meaning of which is unclear. Specifically, it is unclear if the limitations in the parentheses are intended to limit the claim. For example, are all compounds that are polyoxyethylene ethers intended to be included in the claimed subject matter, or just those that are also “known as … Brij”? Since the ordinary artisan would not be able to determine the metes and bounds of the claim, it is indefinite.
Claims 3 and 4 contain the trademarks/trade names for various detergents. Where a trademark or trade name is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph. See Ex parte Simpson, 218 USPQ 1020 (Bd. App. 1982). The claim scope is uncertain since the trademark or trade name cannot be used properly to identify any particular material or product. A trademark or trade name is used to identify a source of goods, and not the goods themselves. Thus, a trademark or trade name does not identify or describe the goods associated with the trademark or trade name. In the present case, the trademarks/trade names are used to identify/describe the source of cell lysis reagents and, accordingly, the identification/description is indefinite.
Specifically, claim 3 and 4 recite the following trademarks: TERGITOL [X], TRITON [X], IGEPAL [X], BRIJ [X], TWEEN [X], GENAPOL [X].
Claim 5 recites the limitation “preferably in the range of 0.001% to 1% (w/v)”, the meaning of which is unclear. Specifically, the phrase "preferably" renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173.05(d). That is, it is unclear whether the narrower range of 0.001% to 1% (w/v) is required as part of the invention. Since the ordinary artisan would not be able to determine the metes and bounds of the claim, it is indefinite.
Claim 8 recites the limitation “such as a micro-well … ”, the meaning of which is unclear. Specifically, the phrase "such as" renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173.05(d). That is, it is unclear whether the compartment is limited to those recited in the claim. Since the ordinary artisan would not be able to determine the metes and bounds of the claim, it is indefinite.
Claim 13 depends from claim 8, and consequently incorporates the indefiniteness issues of claim 8.
Claim 15 recites the limitation “a kit … comprising the reaction composition of claim 6”. However, claim 6 is directed to a method, not a reaction composition. Thus, the meaning of claim 15 cannot be ascertained. Since the ordinary artisan would not be able to determine the metes and bounds of the claim, it is indefinite.
For the purposes of further examination, claim 15 is being construed as depending from claim 5.
Lack of antecedent basis rejections
Claim 1 recites the limitation "the said triterpene glycoside" in l. 3. There is insufficient antecedent basis for this limitation in the claim. Claim 1 does not previously recite a “triterpene glycoside”.
Claims 2-5 and 14 depend from claim 1, and consequently incorporate the lack of
antecedent basis issue of claim 1. Claim 15 is also being construed as depending indirectly from claim 1 (see below).
Claim 4 recites the limitation “the second amphiphile” in l. 4. There is insufficient
antecedent basis for this limitation. Claim 1, from which claim 4 depends, does not recite a “second amphiphile”. Similarly, claim 5 recites “the second amphiphile” in l. 2 and is rejected with the same reasoning.
Claim 7 recites the limitation “the second … amphiphile” in l. 2. There is insufficient
antecedent basis for this limitation. Claim 6, from which claim 7 depends, does not recite a “second amphiphile”.
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 14-15 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 14 recites a “kit … comprising the composition of claim 1”. While the instant
specification recites various optional components that kits may include, e.g., enzymes, buffers, oligonucleotides, consumables and instructions for use (p. 12, ll. 16-19), the specification does not define the term “kit” to require any of these additional components. Thus, at least some embodiments of the “kit” in claim 14 need not comprise any components other than the recited “composition of claim 1”, and these embodiments do not further limit claim 1. Thus, to the extent that claim 14 is directed to such embodiments, it is in improper dependent form. Claim 15 (which is being interpreted as depending from claim 5) similarly recites a “kit”, and is rejected with corresponding reasoning.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
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, 12 and 14-15 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Raybuck (WO 98/26284 A1).
Regarding independent claim 1 and dependent claims 2-5 and 14-15, as noted above,
these claims contain many indefinite limitations, however, Raybuck teaches a composition of a cell lysis reagent comprising a first amphiphile that preferentially binds to fatty acids, phospholipids, glycolipids, and/or sterols, and that binds cholesterol, wherein the said triterpene glycoside amphiphile does not lower activity of the enzymatic reaction 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%, specifically saponin; and further comprises a second amphiphile that is non-ionic and belongs to the class of detergents consisting of Tritons, specifically TRITON X100 (p. 10, ll. 15-26; claims 5-7). Raybuck additionally teaches that the concentration of the first amphiphile is in the range of 0.00001% to 10% (w/v), and preferably in the range of 0.001% to 1% (w/v) (p. 11, ll. 20-24; claims 5-7: 0.01-0.1 wt% saponin). Raybuck additionally teaches a kit comprising the cell lysis composition (p. 14, ll. 12-15), and a reaction composition comprising the cell lysis composition (p. 12, ll. 6-29; p. 14, ll. 12-15; claims 5-7, 11; Examples 1-2).
Regarding independent claim 6 and dependent claim 12, Raybuck teaches a method of cell lysis and DNA synthesis, where the method comprises the steps: adding cells, cell lysis reagent and DNA synthesis reagents to a reaction mixture, lysing the cells to release the desired component from the cells, wherein the desired component is nucleic acid; and replicating and/or amplifying the nucleic acid using PCR (p. 8, ll. 13-16; p. 12, ll. 6-29; p. 14, ll. 12-15; claims 5-7, 11; Examples 1-2).
Claims 6, 8 and 10-13 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Weitz (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 reagent and DNA synthesis reagents to a reaction mixture, lysing the cells to release the desired component from the cells, wherein the desired component is nucleic acid; and reverse transcribing, synthesizing, replicating and/or amplifying the nucleic acid using PCR, quantitative PCR, or RT-PCR. Weitz additionally teaches that the reaction mixture is loaded into a microreactor such as 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 a molecular tag, and some droplets comprise cells and beads, and wherein: (ii) 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 (iii) the molecular tag of the bead in one droplet is distinguishable from the molecular tags of the beads in the other droplets; (iv) lysing the cells; and (v) 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 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 on
single- cells comprises the steps:(i) adding cells, DNA barcodes, cell lysis reagents and DNA synthesis reagents in 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 1-15 are being examined and are rejected. Claims 1, 6-7, 9-10 and 12-13 are objected to. No claims are allowed.
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