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 .
Response to Amendment
The amendment filed December 29th, 2025 is acknowledged. Regarding the Office Action mailed October 2nd, 2025:
The objections to the specification are withdrawn in view of the amendments.
The objections to the claims are withdrawn in view of the amendments and cancellation of claims.
The rejections set forth under 35 U.S.C. 112(b) are withdrawn in view of the amendments, arguments, and cancellation of claims.
Maintained, modified, or new rejections are set forth below, as necessitated by the amendments. Responses to arguments, if necessary, follow their respective rejection sections.
Claim Summary
Claims 1, 4, 14, 16-19, and 22 have been amended. Claims 2-3, 5, 10-13, 20-21, and 23 have been canceled. Claims 26-36 have been added. Claims 1, 4, 6-9, 14-19, 22, and 24-36 are pending. Claims 1, 4, 6-9, 14-19, 22, and 24-36 are under examination and discussed in this Office action.
Claim Rejections - 35 USC § 112(b) - New - 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, 6-9, 14-19, 22, and 24-36 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.
Claims 1, 4, 18, 19, 22, and 36 all recite some variation of a “…a stabilizing solution consisting of a mixture of the two chaotropic salts…” or “…a stabilizing solution consisting of a mixture of the three chaotropic salts…”. It is unclear from these recitations how a stabilizing solution consisting of a mixture of two or three salts can be considered a solution when there is no solvent, such as water, listed as a part of the solution. As stated in MPEP 2111.03(III), “When the phrase "consisting of" appears in a clause of the body of a claim, rather than immediately following the preamble, there is an "exceptionally strong presumption that a claim term set off with ‘consisting of’ is closed to unrecited elements." Multilayer Stretch Cling Film Holdings, Inc. v. Berry Plastics Corp., 831 F.3d 1350, 1359, 119 USPQ2d 1773, 1781 (Fed. Cir. 2016). Given this consideration of “consisting of” language from the MPEP, the solution as currently claimed can only consist of either the two salts guanidinium hydrochloride and guanidinium thiocyanate, or the three salts three chaotropic salts guanidinium thiocyanate, guanidinium hydrochloride and sodium perchlorate, depending on the claim. As defined by Purdue (What Is a Solution? [online]. Purdue, [2026] [retrieved on April 10th, 2026]. Retrieved from: https://www.chem.purdue.edu/gchelp/solutions/whatis.html), “A solution is a homogenous mixture of one or more solutes dissolved in a solvent.” (Page 1). Without a solvent, the salts would remain in solid form, which is not a solution as defined. Therefore, these recitations are found indefinite. Claims 6-9, 14-17, 22, and 24-35 are also rejected here for their dependence on claims 1, 4, 18, or 22 and not further clarifying the identified issue. For the purpose of compact prosecution, instances of “consisting of” appearing in the context of “…a stabilizing solution consisting of a mixture of the two chaotropic salts…” or “…a stabilizing solution consisting of a mixture of the three chaotropic salts…” will be interpreted as “comprising”.
Claim Rejections - 35 USC § 103 - Modified - Necessitated by Amendment
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.
Claims 1, 4, 18, 19, 22, 24-27, and 36 are rejected under 35 U.S.C. 103 as being unpatentable over Fischer (US 20130260369 A1; previously cited).
Regarding instant claim 1, Fischer teaches a method for stabilizing and isolating nucleic acids from a nucleic acid-containing biological sample which comprises adding to said sample, prior to subjecting it to a separation procedure, a sufficient amount of a stabilizing solution (Page 3, paragraphs [0019]-[0020]; Pages 9-10, paragraph [0061]) consisting of a mixture of the two chaotropic salts guanidinium hydrochloride and guanidinium thiocyanate (Page 3, paragraph [0022]); Pages 3-4, paragraph [0023]; see 112(b) interpretation).
Fischer does not directly teach wherein the sum of the molarity of said two chaotropic salts in the stabilizing solution is at least about 2.4 M, and wherein the stabilizing solution contains each of said chaotropic salts, independently from each other, at concentrations from about 1.2 M to about 2.4 M. However, Fischer does teach that the concentration of one or more chaotropes, which may comprise guanidinium hydrochloride and guanidinium thiocyanate (Pages 3-4, paragraph [0023]), is preferably present in the composition in an amount from about 0.5M to about 6M. Fischer also further teaches the more specific concentration of 3M of a chaotrope (Page 5, paragraph [0036]). Given these teachings, arriving at the claimed concentration range of 1.2M and 2.4M total chaotropic salt, as well as 1.2M to 2.4M for each individual chaotropic salt, would amount to routine optimization of the concentrations. It is noted that the courts have found that “where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). See MPEP 2144.05 II. Thus, the claimed range merely represents routine optimization of the values of the cited prior art. It would be obvious to try different concentrations within that provided range, with the provided knowledge of more exemplary concentrations, because it would be choosing from a finite number of solutions. One of ordinary skill in the art would be able to accomplish optimization of concentrations with a reasonable expectation of success. (see MPEP 2141(III))
Regarding instant claim 4, Fischer teaches a method for stabilizing and isolating nucleic acids from a nucleic acid-containing biological sample which comprises adding to said sample, prior to subjecting it to a separation procedure, a sufficient amount of a stabilizing solution (Page 3, paragraphs [0019]-[0020]; Pages 9-10, paragraph [0061]) consisting of a mixture of the three chaotropic salts guanidinium thiocyanate, guanidinium hydrochloride and sodium perchlorate (Page 3, paragraph [0022]); Pages 3-4, paragraph [0023]; see 112(b) interpretation).
Fischer does not directly teach wherein the sum of the molarity of said three chaotropic salts in the stabilizing solution is at least about 2.4 M, and wherein the stabilizing solution contains each of said chaotropic salts, independently from each other, at concentrations from about 0.8 M to about 2.4 M. However, Fischer does teach that the concentration of one or more chaotropes, which may comprise guanidinium hydrochloride, guanidinium thiocyanate, and sodium perchlorate (Pages 3-4, paragraph [0023]), is preferably present in the composition in an amount from about 0.5M to about 6M. Fischer also further teaches the more specific concentration of 3M of a chaotrope (Page 5, paragraph [0036]). Given these teachings, arriving at the claimed concentration range of at least 2.4M total chaotropic salt, as well as 0.8M to 2.4M for each individual chaotropic salt, would amount to routine optimization of the concentrations. It is noted that the courts have found that “where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). See MPEP 2144.05 II. Thus, the claimed range merely represents routine optimization of the values of the cited prior art. It would be obvious to try different concentrations within that provided range, with the provided knowledge of more exemplary concentrations, because it would be choosing from a finite number of solutions. One of ordinary skill in the art would be able to accomplish optimization of concentrations with a reasonable expectation of success. (see MPEP 2141(III))
Regarding instant claim 18, Fischer teaches a stabilizing solution (Page 3, paragraphs [0019]-[0020]) consisting of a mixture of the two chaotropic salts guanidinium hydrochloride and guanidinium thiocyanate (Page 3, paragraph [0022]; Pages 3-4, paragraph [0023]; see 112(b) interpretation).
Fischer does not directly teach wherein the sum of the molarity of said two chaotropic salts in the stabilizing solution is at least about 2.4 M, and wherein the stabilizing solution comprises each of said chaotropic salts, independently from each other, at concentrations from about 1.2 M to about 2.4 M. However, Fischer does teach that the concentration of one or more chaotropes, which may comprise guanidinium hydrochloride and guanidinium thiocyanate (Pages 3-4, paragraph [0023]), is preferably present in the composition in an amount from about 0.5M to about 6M. Fischer also further teaches the more specific concentration of 3M of a chaotrope (Page 5, paragraph [0036]). Given these teachings, arriving at the claimed concentration range of 1.2M and 2.4M total chaotropic salt, as well as 1.2M to 2.4M for each individual chaotropic salt, would amount to routine optimization of the concentrations. It is noted that the courts have found that “where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). See MPEP 2144.05 II. Thus, the claimed range merely represents routine optimization of the values of the cited prior art. It would be obvious to try different concentrations within that provided range, with the provided knowledge of more exemplary concentrations, because it would be choosing from a finite number of solutions. One of ordinary skill in the art would be able to accomplish optimization of concentrations with a reasonable expectation of success. (see MPEP 2141(III))
Regarding instant claim 19, Fischer teaches a sample collection container (Pages 6-7, paragraphs [0048]-[0049]) comprising the stabilizing solution (Page 3, paragraphs [0019]-[0020]; Pages 6-7, paragraphs [0048]-[0049]) consisting of a mixture of the two chaotropic salts guanidinium hydrochloride and guanidinium thiocyanate (Page 3, paragraph [0022]; Pages 3-4, paragraph [0023]; see 112(b) interpretation).
Fischer does not directly teach wherein the sum of the molarity of said two chaotropic salts in the stabilizing solution is at least about 2.4 M, and wherein the stabilizing solution comprises each of said chaotropic salts, independently from each other, at concentrations from about 1.2 M to about 2.4 M. However, Fischer does teach that the concentration of one or more chaotropes, which may comprise guanidinium hydrochloride and guanidinium thiocyanate (Pages 3-4, paragraph [0023]), is preferably present in the composition in an amount from about 0.5M to about 6M. Fischer also further teaches the more specific concentration of 3M of a chaotrope (Page 5, paragraph [0036]). Given these teachings, arriving at the claimed concentration range of 1.2M and 2.4M total chaotropic salt, as well as 1.2M to 2.4M for each individual chaotropic salt, would amount to routine optimization of the concentrations. It is noted that the courts have found that “where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). See MPEP 2144.05 II. Thus, the claimed range merely represents routine optimization of the values of the cited prior art. It would be obvious to try different concentrations within that provided range, with the provided knowledge of more exemplary concentrations, because it would be choosing from a finite number of solutions. One of ordinary skill in the art would be able to accomplish optimization of concentrations with a reasonable expectation of success. (see MPEP 2141(III))
Regarding instant claim 22, Fischer teaches a stabilizing solution (Page 3, paragraphs [0019]-[0020]) consisting of a mixture of the three chaotropic salts guanidinium hydrochloride, guanidinium thiocyanate, and sodium perchlorate (Page 3, paragraph [0022]; Pages 3-4, paragraph [0023]; see 112(b) interpretation).
Fischer does not directly teach wherein the sum of the molarity of said three chaotropic salts in the stabilizing solution is at least about 2.4 M, and wherein the stabilizing solution comprises each of said chaotropic salts, independently from each other, at concentrations from about 0.8 M to about 2.4 M. However, Fischer does teach that the concentration of one or more chaotropes, which may comprise guanidinium hydrochloride, guanidinium thiocyanate, and sodium perchlorate (Pages 3-4, paragraph [0023]), is preferably present in the composition in an amount from about 0.5M to about 6M. Fischer also further teaches the more specific concentration of 3M of a chaotrope (Page 5, paragraph [0036]). Given these teachings, arriving at the claimed concentration range at least 2.4M total chaotropic salt, as well as 0.8M to 2.4M for each individual chaotropic salt, would amount to routine optimization of the concentrations. It is noted that the courts have found that “where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). See MPEP 2144.05 II. Thus, the claimed range merely represents routine optimization of the values of the cited prior art. It would be obvious to try different concentrations within that provided range, with the provided knowledge of more exemplary concentrations, because it would be choosing from a finite number of solutions. One of ordinary skill in the art would be able to accomplish optimization of concentrations with a reasonable expectation of success. (see MPEP 2141(III))
Regarding instant claim 24, Fischer teaches a kit comprising the stabilizing solution of claim 18 (Page 3, paragraphs [0019]-[0020]; Page 3, paragraph [0022]; Pages 3-4, paragraph [0023]; Pages 6-7, paragraphs [0048]-[0049]).
Regarding instant claim 25, Fischer teaches the kit of claim 24. Fischer teaches the kit further comprising lysis solutions/buffer (Pages 6-7, paragraphs [0048]-[0049]).
Regarding instant claim 26, Fischer teaches a kit comprising the stabilizing solution of claim 22 (Page 3, paragraphs [0019]-[0020]; Page 3, paragraph [0022]; Pages 3-4, paragraph [0023]; Pages 6-7, paragraphs [0048]-[0049]).
Regarding instant claim 27, Fischer teaches the kit of claim 26. Fischer teaches the kit further comprising lysis solutions/buffer (Pages 6-7, paragraphs [0048]-[0049]).
Regarding instant claim 36, Fischer teaches a sample collection container (Pages 6-7, paragraphs [0048]-[0049]) comprising the stabilizing solution (Page 3, paragraphs [0019]-[0020]; Pages 6-7, paragraphs [0048]-[0049]) consisting of a mixture of the three chaotropic salts guanidinium hydrochloride, guanidinium thiocyanate, and sodium perchlorate (Page 3, paragraph [0022]; Pages 3-4, paragraph [0023]; see 112(b) interpretation).
Fischer does not directly teach wherein the sum of the molarity of said three chaotropic salts in the stabilizing solution is at least about 2.4 M, and wherein the stabilizing solution comprises each of said chaotropic salts, independently from each other, at concentrations from about 0.8 M to about 2.4 M. However, Fischer does teach that the concentration of one or more chaotropes, which may comprise guanidinium hydrochloride, guanidinium thiocyanate, and sodium perchlorate (Pages 3-4, paragraph [0023]), is preferably present in the composition in an amount from about 0.5M to about 6M. Fischer also further teaches the more specific concentration of 3M of a chaotrope (Page 5, paragraph [0036]). Given these teachings, arriving at the claimed concentration range of at least 2.4M total chaotropic salt, as well as 0.8M to 2.4M for each individual chaotropic salt, would amount to routine optimization of the concentrations. It is noted that the courts have found that “where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). See MPEP 2144.05 II. Thus, the claimed range merely represents routine optimization of the values of the cited prior art. It would be obvious to try different concentrations within that provided range, with the provided knowledge of more exemplary concentrations, because it would be choosing from a finite number of solutions. One of ordinary skill in the art would be able to accomplish optimization of concentrations with a reasonable expectation of success. (see MPEP 2141(III))
Claims 6-9, 14-17, and 28-35 are rejected under 35 U.S.C. 103 as being unpatentable over Fischer (US 20130260369 A1; previously cited), as applied to claims 1, 4, 18, 19, 22, 24-27, and 36, in view of Helftenbein (US 20130066234 A1; previously cited).
Regarding instant claim 6, Fischer teaches the method of claim 1.
Fischer does not teach wherein the stabilizing solution is added to the sample in an amount about equal or greater than the volume of the sample.
Helftenbein, in the same field of endeavor, teaches adding stabilizing solution to the sample in an amount about equal or greater than the volume of the sample (Page 2, paragraph [0035]: blood in an amount 0.1-1 times the solution would reasonably mean the stabilizing solution is in an amount about equal or greater than the volume of the sample).
It would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to have modified the method of Fischer with the amount of stabilization solution of Helftenbein. Since both Fischer and Helftenbein teach on stabilization solutions for biological samples and their use, one of ordinary skill in the art would combine the two teachings with a reasonable expectation of success. One of ordinary skill in the art would have been motivated to make this modification because it amounts to combining prior art elements according to known methods to yield predictable results (see MPEP 2141(III)). It would have been reasonably predictable to one of ordinary skill in the art that the method of Fischer could be used with a stabilization solution and sample volumes taught by Helftenbein. Furthermore, determining the amount of stabilization solution to use would amount to routine optimization. It is noted that the courts have found that “where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). See MPEP 2144.05 II. Thus, the claimed amount of stabilization solution merely represents routine optimization of the values of the cited prior art. It would be obvious to try different volumes within that provided range because it would be choosing from a finite number of solutions. One of ordinary skill in the art would be able to accomplish optimization of volumes with a reasonable expectation of success. (see MPEP 2141(III))
Regarding instant claim 7, Fischer teaches the method of claim 1.
Fischer does not teach wherein the stabilizing solution is added to the sample in an amount of about three-times the volume of the sample.
Helftenbein, in the same field of endeavor, teaches adding stabilizing solution to the sample in an amount of about three-times the volume of the sample (Page 2, paragraph [0035]: blood in an amount 0.33 times the solution would reasonably mean the stabilizing solution is in an amount of about three-times the volume of the sample).
It would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to have modified the method of Fischer with the amount of stabilization solution of Helftenbein. Since both Fischer and Helftenbein teach on stabilization solutions for biological samples and their use, one of ordinary skill in the art would combine the two teachings with a reasonable expectation of success. One of ordinary skill in the art would have been motivated to make this modification because it amounts to combining prior art elements according to known methods to yield predictable results (see MPEP 2141(III)). It would have been reasonably predictable to one of ordinary skill in the art that the method of Fischer could be used with a stabilization solution and sample volumes taught by Helftenbein. Furthermore, determining the amount of stabilization solution to use would amount to routine optimization. It is noted that the courts have found that “where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). See MPEP 2144.05 II. Thus, the claimed amount of stabilization solution merely represents routine optimization of the values of the cited prior art. It would be obvious to try different volumes within that provided range because it would be choosing from a finite number of solutions. One of ordinary skill in the art would be able to accomplish optimization of volumes with a reasonable expectation of success. (see MPEP 2141(III))
Regarding instant claim 8, Fischer teaches the method of claim 1. Fischer further teaches the method comprising (a) providing the nucleic acid-containing sample (Page 3, paragraphs [0019]-[0020]; Pages 9-10, paragraph [0061]), (b) stabilizing the sample of step (a) by adding a sufficient amount of the stabilizing solution, optionally prior to, concomitant with, and/or after lysing the sample by the addition of a distinct lysis buffer and/or lysis solution (Page 3, paragraphs [0019]-[0020]; Pages 9-10, paragraph [0061]).
Fischer does not teach (c) loading the stabilized sample of step (b) to a separation material to bind the nucleic acids to the separation material; (d) washing the separation material with bound nucleic acids by adding one or more wash buffers to remove unwanted materials; and (e) releasing the nucleic acids from the separation material by applying a release solution.
Helftenbein, in the same field of endeavor, teaches on stabilizing blood samples with a stabilization solution in a withdrawal vessel that lyses the blood (Pages 1-2, paragraph [0019]). This lysate is then put in another vessel, wherein magnetic particles and hybridization buffer are added and incubated together (Page 3, paragraph [0054]). Magnetic particles are separated with a magnet, the supernatant is removed, and wash buffer is added (Page 3, paragraph [0054]). The particles are washed 3 times with the wash buffer, then heated in distilled water to remove the isolated mRNA (Page 3, paragraph [0054]).
It would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to have modified the method of Fischer with the separation steps of Helftenbein. Since both Fischer and Helftenbein teach on stabilization solutions for biological samples and their use, one of ordinary skill in the art would combine the two teachings with a reasonable expectation of success. One of ordinary skill in the art would have been motivated to make this modification because it amounts to combining prior art elements according to known methods to yield predictable results (see MPEP 2141(III)). It would have been reasonably predictable to one of ordinary skill in the art that the method of Fischer could be used with a separate separation step like that taught by Helftenbein.
Regarding instant claim 9, Fischer, in view of Helftenbein, teaches the method of claim 8. Helftenbein further teaches wherein the separation material is magnetic beads, step (d) comprises separating the beads from the sample by magnetic bead separation (Page 3, paragraph [0054]); and washing the separated beads with one or more wash buffers (Page 3, paragraph [0054]), and step (e) comprises releasing the nucleic acids from the separated beads by applying a release solution (Page 3, paragraph [0054]). The analysis applied for claim 8 also applies here.
Regarding instant claim 14, Fischer, in view of Helftenbein, teaches the method of claim 8.
Neither reference as yet presented teaches wherein the stabilizing solution is added to the sample in an amount about equal or greater than the volume of the sample.
Helftenbein, in the same field of endeavor, teaches adding stabilizing solution to the sample in an amount about equal or greater than the volume of the sample (Page 2, paragraph [0035]: blood in an amount 0.1-1 times the solution would reasonably mean the stabilizing solution is in an amount about equal or greater than the volume of the sample).
It would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to have modified the method of Fischer with the amount of stabilization solution of Helftenbein. Since both Fischer and Helftenbein teach on stabilization solutions for biological samples and their use, one of ordinary skill in the art would combine the two teachings with a reasonable expectation of success. One of ordinary skill in the art would have been motivated to make this modification because it amounts to combining prior art elements according to known methods to yield predictable results (see MPEP 2141(III)). It would have been reasonably predictable to one of ordinary skill in the art that the method of Fischer could be used with a stabilization solution and sample volumes taught by Helftenbein. Furthermore, determining the amount of stabilization solution to use would amount to routine optimization. It is noted that the courts have found that “where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). See MPEP 2144.05 II. Thus, the claimed amount of stabilization solution merely represents routine optimization of the values of the cited prior art. It would be obvious to try different volumes within that provided range because it would be choosing from a finite number of solutions. One of ordinary skill in the art would be able to accomplish optimization of volumes with a reasonable expectation of success. (see MPEP 2141(III))
Regarding instant claim 15, Fischer, in view of Helftenbein, teaches the method of claim 8. Helftenbein further teaches wherein the wash buffers of step (d) are salt-containing aqueous solutions (Page 3, paragraph [0054]). The analysis for claim 8 also applies here.
Regarding instant claim 16, Fischer, in view of Helftenbein, teaches the method of claim 8. Helftenbein further teaches wherein the release solution is water (Page 3, paragraph [0054]). The analysis for claim 8 also applies here.
Regarding instant claim 17, Fischer, in view of Helftenbein, teaches the method of claim 14.
Fischer does not teach wherein the stabilizing solution is added to the sample in an amount of about three-times the volume of the sample.
Helftenbein, in the same field of endeavor, teaches adding stabilizing solution to the sample in an amount of about three-times the volume of the sample (Page 2, paragraph [0035]: blood in an amount 0.33 times the solution would reasonably mean the stabilizing solution is in an amount of about three-times the volume of the sample).
It would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to have modified the method of Fischer with the amount of stabilization solution of Helftenbein. Since both Fischer and Helftenbein teach on stabilization solutions for biological samples and their use, one of ordinary skill in the art would combine the two teachings with a reasonable expectation of success. One of ordinary skill in the art would have been motivated to make this modification because it amounts to combining prior art elements according to known methods to yield predictable results (see MPEP 2141(III)). It would have been reasonably predictable to one of ordinary skill in the art that the method of Fischer could be used with a stabilization solution and sample volumes taught by Helftenbein. Furthermore, determining the amount of stabilization solution to use would amount to routine optimization. It is noted that the courts have found that “where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). See MPEP 2144.05 II. Thus, the claimed amount of stabilization solution merely represents routine optimization of the values of the cited prior art. It would be obvious to try different volumes within that provided range because it would be choosing from a finite number of solutions. One of ordinary skill in the art would be able to accomplish optimization of volumes with a reasonable expectation of success. (see MPEP 2141(III))
Regarding instant claim 28, Fischer teaches the method of claim 4.
Fischer does not teach wherein the stabilizing solution is added to the sample in an amount about equal or greater than the volume of the sample.
Helftenbein, in the same field of endeavor, teaches adding stabilizing solution to the sample in an amount about equal or greater than the volume of the sample (Page 2, paragraph [0035]: blood in an amount 0.1-1 times the solution would reasonably mean the stabilizing solution is in an amount about equal or greater than the volume of the sample).
It would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to have modified the method of Fischer with the amount of stabilization solution of Helftenbein. Since both Fischer and Helftenbein teach on stabilization solutions for biological samples and their use, one of ordinary skill in the art would combine the two teachings with a reasonable expectation of success. One of ordinary skill in the art would have been motivated to make this modification because it amounts to combining prior art elements according to known methods to yield predictable results (see MPEP 2141(III)). It would have been reasonably predictable to one of ordinary skill in the art that the method of Fischer could be used with a stabilization solution and sample volumes taught by Helftenbein. Furthermore, determining the amount of stabilization solution to use would amount to routine optimization. It is noted that the courts have found that “where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). See MPEP 2144.05 II. Thus, the claimed amount of stabilization solution merely represents routine optimization of the values of the cited prior art. It would be obvious to try different volumes within that provided range because it would be choosing from a finite number of solutions. One of ordinary skill in the art would be able to accomplish optimization of volumes with a reasonable expectation of success. (see MPEP 2141(III))
Regarding instant claim 29, Fischer teaches the method of claim 4.
Fischer does not teach wherein the stabilizing solution is added to the sample in an amount of about three-times the volume of the sample.
Helftenbein, in the same field of endeavor, teaches adding stabilizing solution to the sample in an amount of about three-times the volume of the sample (Page 2, paragraph [0035]: blood in an amount 0.33 times the solution would reasonably mean the stabilizing solution is in an amount of about three-times the volume of the sample).
It would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to have modified the method of Fischer with the amount of stabilization solution of Helftenbein. Since both Fischer and Helftenbein teach on stabilization solutions for biological samples and their use, one of ordinary skill in the art would combine the two teachings with a reasonable expectation of success. One of ordinary skill in the art would have been motivated to make this modification because it amounts to combining prior art elements according to known methods to yield predictable results (see MPEP 2141(III)). It would have been reasonably predictable to one of ordinary skill in the art that the method of Fischer could be used with a stabilization solution and sample volumes taught by Helftenbein. Furthermore, determining the amount of stabilization solution to use would amount to routine optimization. It is noted that the courts have found that “where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). See MPEP 2144.05 II. Thus, the claimed amount of stabilization solution merely represents routine optimization of the values of the cited prior art. It would be obvious to try different volumes within that provided range because it would be choosing from a finite number of solutions. One of ordinary skill in the art would be able to accomplish optimization of volumes with a reasonable expectation of success. (see MPEP 2141(III))
Regarding instant claim 30, Fischer teaches the method of claim 4. Fischer further teaches the method comprising (a) providing the nucleic acid-containing sample (Page 3, paragraphs [0019]-[0020]; Pages 9-10, paragraph [0061]), (b) stabilizing the sample of step (a) by adding a sufficient amount of the stabilizing solution, optionally prior to, concomitant with, and/or after lysing the sample by the addition of a distinct lysis buffer and/or lysis solution (Page 3, paragraphs [0019]-[0020]; Pages 9-10, paragraph [0061]).
Fischer does not teach (c) loading the stabilized sample of step (b) to a separation material to bind the nucleic acids to the separation material; (d) washing the separation material with bound nucleic acids by adding one or more wash buffers to remove unwanted materials; and (e) releasing the nucleic acids from the separation material by applying a release solution.
Helftenbein, in the same field of endeavor, teaches on stabilizing blood samples with a stabilization solution in a withdrawal vessel that lyses the blood (Pages 1-2, paragraph [0019]). This lysate is then put in another vessel, wherein magnetic particles and hybridization buffer are added and incubated together (Page 3, paragraph [0054]). Magnetic particles are separated with a magnet, the supernatant is removed, and wash buffer is added (Page 3, paragraph [0054]). The particles are washed 3 times with the wash buffer, then heated in distilled water to remove the isolated mRNA (Page 3, paragraph [0054]).
It would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to have modified the method of Fischer with the separation steps of Helftenbein. Since both Fischer and Helftenbein teach on stabilization solutions for biological samples and their use, one of ordinary skill in the art would combine the two teachings with a reasonable expectation of success. One of ordinary skill in the art would have been motivated to make this modification because it amounts to combining prior art elements according to known methods to yield predictable results (see MPEP 2141(III)). It would have been reasonably predictable to one of ordinary skill in the art that the method of Fischer could be used with a separate separation step like that taught by Helftenbein.
Regarding instant claim 31, Fischer, in view of Helftenbein, teaches the method of claim 30. Helftenbein further teaches wherein the separation material is magnetic beads, step (d) comprises separating the beads from the sample by magnetic bead separation (Page 3, paragraph [0054]); and washing the separated beads with one or more wash buffers (Page 3, paragraph [0054]), and step (e) comprises releasing the nucleic acids from the separated beads by applying a release solution (Page 3, paragraph [0054]). The analysis applied for claim 30 also applies here.
Regarding instant claim 32, Fischer, in view of Helftenbein, teaches the method of claim 30.
Neither reference as yet presented teaches wherein the stabilizing solution is added to the sample in an amount about equal or greater than the volume of the sample.
Helftenbein, in the same field of endeavor, teaches adding stabilizing solution to the sample in an amount about equal or greater than the volume of the sample (Page 2, paragraph [0035]: blood in an amount 0.1-1 times the solution would reasonably mean the stabilizing solution is in an amount about equal or greater than the volume of the sample).
It would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to have modified the method of Fischer with the amount of stabilization solution of Helftenbein. Since both Fischer and Helftenbein teach on stabilization solutions for biological samples and their use, one of ordinary skill in the art would combine the two teachings with a reasonable expectation of success. One of ordinary skill in the art would have been motivated to make this modification because it amounts to combining prior art elements according to known methods to yield predictable results (see MPEP 2141(III)). It would have been reasonably predictable to one of ordinary skill in the art that the method of Fischer could be used with a stabilization solution and sample volumes taught by Helftenbein. Furthermore, determining the amount of stabilization solution to use would amount to routine optimization. It is noted that the courts have found that “where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). See MPEP 2144.05 II. Thus, the claimed amount of stabilization solution merely represents routine optimization of the values of the cited prior art. It would be obvious to try different volumes within that provided range because it would be choosing from a finite number of solutions. One of ordinary skill in the art would be able to accomplish optimization of volumes with a reasonable expectation of success. (see MPEP 2141(III))
Regarding instant claim 33, Fischer, in view of Helftenbein, teaches the method of claim 30. Helftenbein further teaches wherein the wash buffers of step (d) are salt-containing aqueous solutions (Page 3, paragraph [0054]). The analysis for claim 30 also applies here.
Regarding instant claim 34, Fischer, in view of Helftenbein, teaches the method of claim 30. Helftenbein further teaches wherein the release solution is water (Page 3, paragraph [0054]). The analysis for claim 30 also applies here.
Regarding instant claim 35, Fischer, in view of Helftenbein, teaches the method of claim 32.
Neither reference as yet presented teaches wherein the stabilizing solution is added to the sample in an amount of about three-times the volume of the sample.
Helftenbein, in the same field of endeavor, teaches adding stabilizing solution to the sample in an amount of about three-times the volume of the sample (Page 2, paragraph [0035]: blood in an amount 0.33 times the solution would reasonably mean the stabilizing solution is in an amount of about three-times the volume of the sample).
It would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to have modified the method of Fischer with the amount of stabilization solution of Helftenbein. Since both Fischer and Helftenbein teach on stabilization solutions for biological samples and their use, one of ordinary skill in the art would combine the two teachings with a reasonable expectation of success. One of ordinary skill in the art would have been motivated to make this modification because it amounts to combining prior art elements according to known methods to yield predictable results (see MPEP 2141(III)). It would have been reasonably predictable to one of ordinary skill in the art that the method of Fischer could be used with a stabilization solution and sample volumes taught by Helftenbein. Furthermore, determining the amount of stabilization solution to use would amount to routine optimization. It is noted that the courts have found that “where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). See MPEP 2144.05 II. Thus, the claimed amount of stabilization solution merely represents routine optimization of the values of the cited prior art. It would be obvious to try different volumes within that provided range because it would be choosing from a finite number of solutions. One of ordinary skill in the art would be able to accomplish optimization of volumes with a reasonable expectation of success. (see MPEP 2141(III))
Response to Arguments
Applicant's arguments filed December 29th, 2025 have been fully considered but they are not persuasive.
The Applicant first acknowledges the Examiner’s previous rejection (Page 10 of the Remarks filed December 29th, 2025). The Applicant then recites requirements for establishing a prima facie case of obviousness (Page 10 of the Remarks filed December 29th, 2025). The Applicant argues that as amended, the claims now require a stabilizing solution consisting of a mixture of either two chaotropic salts or three chaotropic salts with particular molarity ranges (Pages 10 and 11 of the Remarks filed December 29th, 2025). The Applicant cites the Examiner’s previous rejection using the reference Fischer to teach a solution comprising a mixture of either two chaotropic salts or three chaotropic salts and the routine optimization of particular molarity ranges (Page 11 of the Remarks filed December 29th, 2025). The Applicant disagrees with this rejection, arguing that now the pending claims use consisting of language and Fischer’s solution contains more than the claimed chaotropic salts (Pages 11 and 12 of the Remarks filed December 29th, 2025). The Applicant further argues that there is no motivation present in Fischer that all but the chaotropic salts could be removed from Fischer’s solution and still have a stabilization solution with the same properties (Page 12 of the Remarks filed December 29th, 2025). The Applicant then states that the claimed invention is based on a synergistic effect between chaotropic salts previously unknown and not suggested by the literature, citing aspects of the invention detailed in the instant specification that show benefit over more complex mixtures (Pages 12 and 13 of the Remarks filed December 29th, 2025). The Applicant argues that the advantages of the simpler solution claimed cannot be fairly called expected or routine optimization, and therefore there is no reasonable expectation of success and no prima facie case of obviousness can be established using Fischer (Page 13 of the Remarks filed December 29th, 2025). The Applicant also argues that Helftenbein cannot cure the deficiencies of Fischer (Page 13 of the Remarks filed December 29th, 2025).
In response to these arguments, it is noted that, given the issues addressed in the 112(b) rejection above, the consisting of language introduced by the amendments have made the claims indefinite. The Examiner directs the Applicant back to the 112(b) rejection for an explanation regarding this indefiniteness, and also reiterates that, for the purpose of compact prosecution, instances of “consisting of” appearing in context such as “…a stabilizing solution consisting of a mixture of the two chaotropic salts…” or “…a stabilizing solution consisting of a mixture of the three chaotropic salts…” will be interpreted as “comprising”. Because the Applicant’s arguments are directed to the consisting of language limiting the solution to the claimed chaotropic salts and the deficiencies of Fischer related to the consisting of language, the arguments are found unpersuasive until the indefiniteness related to the consisting of language has been resolved.
Conclusion
All claims stand rejected.
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.
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/ALLISON E SCHLOOP/Examiner, Art Unit 1683
/ANNE M. GUSSOW/Supervisory Patent Examiner, Art Unit 1683
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