DETAILED ACTION
The present Office Action is responsive to the Amendment received on May 22, 2026.
Preliminary Remark
Claims 2, 3, 7, 8, and 10 are canceled.
Claim Rejections - 35 USC § 112 – New Grounds, Necessitated by Amendment
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, 4-6, and 9 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 1 is indefinite because the claim combines a product with its method of use in reciting the phrase, “when a sample containing nucleic acid is added to the composition to prepare a mixture …”.
The Federal Circuit decided an issue of first impression in that Court - whether a patent claim that covers both an apparatus and method of use of that apparatus passes muster under 35 USC §112, para. 2 (indefiniteness). Defending its "1-click system," Amazon won a summary judgment ruling of invalidity, IPXL Holdings, LLC v. Amazon.com, Inc., 333 F. Supp. 2d 513 (E.D. Va. 2004), which the Federal Circuit affirmed in part, 2005 U.S. App. LEXIS 25120.
After upholding the district court's claim constructions and affirming the finding that all but one of the asserted claims were anticipated, the Federal Circuit next affirmed the summary judgment of invalidity (for indefiniteness) for the remaining asserted claim, which read:
25. The system of claim 2 [including an input means] wherein the predicted transaction information comprises both a transaction type and transaction parameters associated with that transaction type, and the user uses the input means to either change the predicted transaction information or accept the displayed transaction type and transaction parameters.
Claim 25 on its face is directed to a "system." However, it also recites use steps ("the user uses the input means to ...change the predicted transaction information ... ") This claim was found indefinite by the district court.
Thus, for the above reasons, instant claim 1 is indefinite.
Claims 4-6 and 9 are indefinite by way of their dependency on claim 1.
Claim Rejections - 35 USC § 102
The rejection of claims 2, 3, and 9 under 35 U.S.C. 102(a)(1) as being anticipated by Bronner et al. (Applied and Environmental Microbiology, September 2000, vol. 66, no. 9, pages 3931-3938) as evidenced by RNaseOUT™ product catalog (on-line product catalogue, available at thermofisher.com/order/catalog/product/10777019, pages 1-7), made in the Office Action mailed on February 25, 2026 is withdrawn in view of the Amendment received on May 22, 2026.
Bronner et al. fail to teach the method of claim 9 wherein the mixture formed is added to a premix and a solution containing primers and probes without separate elution process and purification process.
The rejection of Claim 2 and 3 under 35 U.S.C. 102(a)(1) as being anticipated by van Dijk et al. (PNAS, October 2003, vol. 100, no. 21, pages 12081-12086) made in the Office Action mailed on February 25, 2026 is withdrawn in view of the Amendment received on May 22, 2026, canceling the rejected claims.
Rejection - Maintained
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.
The rejection of claims 1 and 4 under 35 U.S.C. 102(a)(1) as being anticipated by Bronner et al. (Applied and Environmental Microbiology, September 2000, vol. 66, no. 9, pages 3931-3938) as evidenced by RNaseOUT™ product catalog (on-line product catalogue, available at thermofisher.com/order/catalog/product/10777019, pages 1-7), made in the Office Action mailed on February 25, 2026 is maintained for the reasons of record.
Applicants’ claim amendment and arguments presented in the Amendment received on May 22, 2026 have been carefully considered but they have not been found persuasive for the reasons discussed in the, “Response to Arguments” section.
The Rejection:
With regard to claims 1 and 4, Bronner et al. teach a composition comprising an RNAse inhibitor and a buffer (“RNA preparation was resuspended in 0.5 mM EDTA (pH 7.5) plus 40U of RNase OUT”, page 3932, 1st column).
RNAseOUT is an RNase A inhibitor and derived from a protein (“RNaseOUT Recombinant Ribonuclease inhibitor is a potent noncompetitive inhibitor of pancreatic-type ribonucleases such as RNase A … It is an acidic protein”, page 2).
Therefore, Bronner et al. anticipate the invention as claimed.
Response to Arguments:
Applicants traverse the rejection.
Applicants state that the claims as amended are now directed to a composition and method for cell lysis and nucleic acid extraction in which a protein-derived RNase A inhibitor is used in a specific concentration range and the method can proceed without a separate elution or purification process, and contend that Bronner does not disclose a such direct workflow (page 6, Response).
Applicants state that the amended claims are not directly merely to the presence of RNaseOUT and a buffer, but requires a protein-derived RNAse A inhibitor in a defined concentration range of 30.0 to 45.0 units/reaction, based on a 30 uL mixture and contend that Bronner does not disclose this concentration range in the context of cell lysis and nucleic acid extraction mixture (page 6, Response).
The Office respectfully disagrees.
With regard to claim 1, the Office respectfully maintains that the claim is drawn to a product, that is, a composition comprised of: 1) an RNase inhibitor; and 2) a buffer. The claim further requires that the RNase inhibitor is an RNase A inhibitor and that it is derived from a protein.
To this end, the composition RNaseOUT™ is a protein-derived inhibitor of an RNase A enzyme, and this enzyme is not sold as a powder, but in a stabilizing buffer, wherein the buffer is at pH 8 (see attached RNAseOUT® catalog, of record).
Contrary to Applicants’ assertion, the limitation following the phrase, “when a sample containing nucleic is added to the composition …” does not further limit the composition as the limitations are only directed to when the composition is employed in a reaction.
Therefore, Bronner et al. anticipate the invention as claimed.
The rejection of claims 1 and 5 under 35 U.S.C. 102(a)(1) as being anticipated by van Dijk et al. (PNAS, October 2003, vol. 100, no. 21, pages 12081-12086), made in the Office Action mailed on February 25, 2026 is maintained for the reasons of record.
Applicants’ claim amendment and arguments presented in the Amendment received on May 22, 2026 have been carefully considered but they have not been found persuasive for the reasons discussed in the, “Response to Arguments” section.
The Rejection:
With regard to claims 1 and 5, van Dijk et al. teach a composition comprising RNaseOUT in the presence of DTT (“reaction buffer, 10 mM DTT, and 20 units of RNaseOUT in a total volume of 10 ml”, page 12082, 2nd column, 2nd paragraph).
RNAseOUT is an RNase A inhibitor and derived from a protein (“RNaseOUT Recombinant Ribonuclease inhibitor is a potent noncompetitive inhibitor of pancreatic-type ribonucleases such as RNase A … It is an acidic protein”, page 2).
Therefore, the invention as claimed is anticipated by van Dijk et al.
Response to Arguments:
Applicants’ arguments directed for van Dijk et al. is identical to that which was already responded to above, that is, the concentration of the composition and the intended usage of the claimed composition, that are not deemed further limiting, and adopt the above-discussed reasoning herein.
Claim Rejections - 35 USC § 103
The rejection of claims 7 and 8 under 35 U.S.C. 103 as being unpatentable over Bronner et al. (Applied and Environmental Microbiology, September 2000, vol. 66, no. 9, pages 3931-3938) as evidenced by RNaseOUT™ product catalog (on-line product catalogue, available at thermofisher.com/order/catalog/product/10777019, pages 1-7) in view of van Dijk et al. (PNAS, October 2003, vol. 100, no. 21, pages 12081-12086), made in the Office Action mailed on February 25, 2026 is withdrawn in view of the Amendment received on May 22, 2026, canceling the rejected claims.
Rejection - Maintained
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 rejection of claim 6 under 35 U.S.C. 103 as being unpatentable over Bronner et al. (Applied and Environmental Microbiology, September 2000, vol. 66, no. 9, pages 3931-3938) as evidenced by RNaseOUT™ product catalog (on-line product catalogue, available at thermofisher.com/order/catalog/product/10777019, pages 1-7) in view of van Dijk et al. (PNAS, October 2003, vol. 100, no. 21, pages 12081-12086) made in the Office Action mailed on February 25, 2026 is maintained for the reasons of record.
Applicants’ claim amendment and arguments presented in the Amendment received on May 22, 2026 have been carefully considered but they have not been found persuasive for the reasons discussed in the, “Response to Arguments” section.
The Rejection:
The teachings of Bronner et al. and RNaseOUT™ have already been discussed above.
Bronner et al. do not teach a second heating temperature of 75oC or higher to 100oC or higher, wherein a first and second heating steps are each performed for 1 to 30 minutes, and the concentration of RNaseOUT™ being at the concentration (claim 6).
van Dijk et al. teach that RNaseOUT™ is denatured at higher temperatures, such as 70oC (“20 units of RNaseOUT in a total volume of 10 mM DTT, and 20 units of RNaseOUT … Reactions were incubated at 42oC … heat inactivated at 70oC for 15 min …”, page 12082, 2nd column).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to apply the teachings of Bronner et al. with the teachings of van Dijk et al. and conventional knowledge available to the one of ordinarily skilled in the art thereby arriving at the invention as claimed for the following reasons.
Bronner et al. actually teach a method of treating a sample with RNaseOUT and incubating at a first temperature between 25oC to 45oC with incubation time of 1-30 minutes:
“40 U of RNase OUT for 30 min at 25oC” (page 3932, 2nd column)
As well, Bronner et al. teach a second incubation condition wherein RNaseOUT is inactivated at an elevated temperature having an incubation time of 1-30 minutes:
“The reaction was stopped by heating at 65oC for 5 min.” (page 3932, 2nd column)
While Bronner et al. did not employ a higher incubation temperature, as demonstrated by van Dijk et al., who employ an elevated temperature close to 75oC at 70oC, one of ordinary skill in the art would have been well-apprised of the knowledge that proteins/enzymes denatured at an elevated temperature. Therefore, one of ordinary skill in the art would have determined that a temperature higher than the ones employed by Bronner et al., such as 75oC or higher would have yielded no more than a predictable outcome of heat inactivating RNaseOUT in Bronner et al.’s reaction.
With regard to the concentration of RNaseOUT in the reaction, Bronner et al. teach that 40U of RNAseOUT is used in a 300 ml volume. However, the Office contends that absent secondary characteristics, the determination of an optimal condition of RNaseOUT in a given reaction for inhibiting RNAse A activity would have been recognized as a result-effective variable.
MPEP 2144.05(II)(B) discusses that in In re Antonie, 559 F.2d 618, 195 USPQ 6 (CCPA 1977), the CCPA held that a particular parameter must first be recognized as a result-effective variable, i.e., a variable which achieves a recognized result, before the determination of the optimum or workable ranges of said variable might be characterized as routine experimentation.
Since the amount of RNaseOUT would have been directly related to the outcome of the RNA molecules being amplified in the RT-PCR assay of Bronner et al., optimization of concentration thereof would have been result-effective, deemed optimizable under the obviousness doctrine.
Therefore, the invention as claimed is deemed prima facie obvious over the cited references.
Response to Arguments:
Applicants traverse the rejection.
Applicants contend that it would not have been obvious to one of ordinary skill in the art to combine the teachings of Bronner and van Dijk because Bronner et al. teach the use of RNaseOUT in the context of conventional RNA preparation and RT-PCR analysis while van Dijk uses RNaseOUT, DTT and reaction buffer in the context of mRNA decapping assays which is technically different from cell lysis and nucleic acid for direct PCR (page 9, Response).
This argument is not found persuasive for the following reasons.
As regard to the usage of Bronner and van Dijk being in the different field of endeavor, the argument is not convincing because the aspect relied on for van Dijk is for the inactivation of the RNase inhibitor not the assay to which van Dijk is directed toward. As already discussed above, Bronner teach that the reaction of RNaseOUT that acts on the RNase A in a sample is inactivated via higher temperature:
“The reaction was stopped by heating at 65oC for 5 min.” (page 3932, 2nd column, Bronner)
And while Bronner did not explicitly teach a range of temperatures that can be employed to inactivate RNaseOUT upon its completion of inactivating RNases in a sample, van Dijk taught that temperature higher than 65oC, such as 75oC yielded the same predictable outcome, providing one of ordinary skill in the art a reasonable expectation of success.
As to the method being utilized in a “direct PCR”, this argument is not found persuasive because claim 6 is not directed to the direct usage of the resulting mixture in a PCR reaction, but simply adding the composition comprising an RNase A inhibitor with a sample, and inactivating the resulting mixture at a higher temperature which has been known to yield a predictable outcome of inactivating RNase A inhibitor upon reaction completion.
To this end, there is no need for the one of ordinary skill in the art to consider whether the mixture of Bronner and van Dijk can be utilized in a PCR reaction directly without further elution or purification.
Therefore, the arguments are not deemed persuasive and the rejection is maintained.
Claims 1, 6, and 9 are rejected under 35 U.S.C. 103 as being unpatentable over Pearson et al. (bioRxiv, May 13, 2020, pages 1-28) in view of RNaseOUT™ product catalog (on-line product catalogue, available at thermofisher.com/order/catalog/product/10777019, pages 1-7), and Bronner et al. (Applied and Environmental Microbiology, September 2000, vol. 66, no. 9, pages 3931-3938).
With regard to claim 1, Pearson et al. teach a composition comprising RNaseOUT, which as discussed above, is an RNAse A inhibitor that is dissolved in a buffer (see RNaseOUT product catalogue).
Pearson et al. teach a method of direct RT-PCR of SARS-CoV-2 from sample without purification, wherein the artisans employ:
preparing a mixture containing RNaseOUT (“2.5 ml of patient sample in universal transport media (UTM, Copan) were added to the RT-qPCR reaction mix … To optimize direct detection RNaseOUT (ThermoFisher) was added to the UTM samples (2U/ml);
heating step of maintaining the mixture at temperature above 75oC or higher to lower than 100oC (“[s]amples were then left untreated, heated at 95oC for 15 minutes … Samples were then directed added to the RT-qPCR reaction mixture” (page 7, bottom to page 8, top); and
amplifying the mixture by PCR (“RT-PCR results”, see page 13), wherein the premix and the solution containing primers and a probe are added to the mixture without a separate elution process and purification process (“RNase inhibitor brought direct RT-qPCR results with the Norgen detection kit to within 3 Ct values (~10 fold) of those obtained with extracted RNA”, page 13).
While Pearson et al. explicitly teach that direct RT-qPCR can be performed directly on samples with RNaseOUT without prior elution or purification, the artisans do not teach a first incubation temperature of 25oC to 45oC (employed room temperature), or the concentration of the RNase inhibitor being 1U to 1.5 U per reaction volume.
Bronner et al. teach that incubation of sample with RNaseOUT occurs at 25oC for 30 minutes (“40U of RNaseOUT for 30 min at 25oC”, page 3932, 2nd column).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Pearson et al., RNaseOUT product catalog, and Bronner et al., thereby arriving at the invention as claimed for the following reasons.
As discussed above, Pearson et al. already teach and provide a reasonable expectation of success at directly performing an RT-qPCR reaction from a sample by combining a composition comprising RNaseOUT (that is, RNase A inhibitor) and combining the RT-PCR mixture thereto. While Pearson et al. did not explicitly teach the amount of RNaseOUT that should be present in a reaction volume in the amount presently claimed or the first incubation temperature, because Pearson et al. taught that the reagent could be employed for such a purpose, as well as Bronner et al. teaching the first incubation temperature of a sample with RNaseOUT, the determination of such optimal condition of RNaseOUT that can work in a direct RT-qPCR would have involved routine optimization by empirical determination.
Since Pearson et al. explicitly evidenced that RNaseOUT is a result-effective variable, that is, an ingredient that is directly responsible for the outcome of direct RT-qPCR without prior sample elution/purification, optimization of such variable would have been well-within the purview of the ordinarily skilled artisan.
In In re Antonie, 559 F.2d 618, 195 USPQ 6 (CCPA 1977), the CCPA held that a particular parameter must first be recognized as a result-effective variable, i.e., a variable which achieves a recognized result, before the determination of the optimum or workable ranges of said variable might be characterized as routine experimentation, because “obvious to try” is not a valid rationale for an obviousness finding.
Therefore, the invention as claimed is deemed prima facie obvious over the cited references.
Conclusion
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.
Inquiries
Any inquiry concerning this communication or earlier communications from the Examiner should be directed to Young J. Kim whose telephone number is (571) 272-0785. The Examiner can best be reached from 7:30 a.m. to 4:00 p.m (M-F). The Examiner can also be reached via e-mail to Young.Kim@uspto.gov. However, the office cannot guarantee security through the e-mail system nor should official papers be transmitted through this route.
If attempts to reach the Examiner by telephone are unsuccessful, the Examiner's supervisor, Gary Benzion, can be reached at (571) 272-0782.
Papers related to this application may be submitted to Art Unit 1681 by facsimile transmission. The faxing of such papers must conform with the notice published in the Official Gazette, 1156 OG 61 (November 16, 1993) and 1157 OG 94 (December 28, 1993) (see 37 CFR 1.6(d)). NOTE: If applicant does submit a paper by FAX, the original copy should be retained by applicant or applicant’s representative. NO DUPLICATE COPIES SHOULD BE SUBMITTED, so as to avoid the processing of duplicate papers in the Office. All official documents must be sent to the Official Tech Center Fax number: (571) 273-8300. Any inquiry of a general nature or relating to the status of this application should be directed to the Group receptionist whose telephone number is (571) 272-1600.
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/YOUNG J KIM/Primary Examiner
Art Unit 1637 July 30, 2026
/YJK/
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