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 .
DETAILED ACTION
Claims dated 02/24/2026 are acknowledged. Claims 1-16 and 18-22 are pending in the instant application and are examined on the merits herein.
The declaration dated 02/24/2026 written by Ralf Wyrich is acknowledged.
Priority
The instant application claims foreign priority to EP21201705.7, filed on 10/08/2021.
Maintained Grounds of Rejection
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.
Claims 1-13, 15-16, and 18-22 are rejected under 35 U.S.C. 103 as being unpatentable over Ching (US8809519 B2, published 08/192014, see PTO-892 dated 06/02/2025), Sprenger-Haussels (US7005266 B2, published 02/282006, see PTO-892 dated 06/02/2025) and The Agency for Toxic Substances and Disease Registry (https://www.ncbi.nlm.nih.gov/books/NBK599456/, published 09/07/2008, accessed 11/18/2025, see PTO-892).
Ching is drawn to a method for isolating nucleic acids using a solid phase (abstract). Ching teaches a method of isolating nucleic acids comprising contacting a sample containing nucleic acids with a solid phase in a first aqueous solution wherein the first aqueous solution comprises one or more salts. The one or more salts could be a combination of chaotropic salts and kosmotropic salts (column 10, lines 26-65). The kosmotropic salt could be ammonium sulfate (AS) (column 11, line 22). The salts in the first aqueous solution could be present in a concentration from about 0.1 M to about 6M (column 12, lines 21-23). Ching teaches that the sample can be pretreated by a lysis step (column 3, line 13). Ching teaches that the solid phase are magnetic particles (column 8, line 56). Ching exemplified a blood sample that was 200 µL of blood diluted to a final volume of 755 µL with the addition of the microbead slurry including AS and a 10mM TRIS HCl buffer, Proteinase K solution, and PEG solution meeting the limitation of an inhibitor removal solution having a volume equal or greater than the volume of the sample and meeting the limitation that the inhibitor removal solution is about three-times the volume of the sample (column 9, lines 24-46). The combined microbead slurry, proteinase K solution, and PEG solution also acts as the binding solution. Ching teaches placing the sample on a magnetic rack to draw the particles to one side, removal of the initial solution, and followed with salt containing aqueous wash buffers (column 9, lines 47-63). Ching teaches the use of water to release the nucleic acids from the magnetic particles (column 10, lines 1-5). Ching teaches a kit comprising a solid phase, one or more salts, one or more buffering agents, and purified water in a container (column 8, lines 16-22).
Ching does not teach the use of PVP. Ching does not teach the weight ratio of PVP component to the AS is from 10:1 to about 1:10, 5:1 to about 1:5, or 1.5:1 to about 1:4.
Sprenger-Haussels is drawn to the method for the stabilization, purification and isolation of nucleic acids from material samples which contain impurities and inhibitors and further relates to a reagent kit for carrying out said method (abstract). Sprenger-Haussels teaches that the purification of nucleic acids from inhibitory samples can be improved by using a specific buffer in order to bind impurities. Sprenger-Hausells further teaches the samples may be obtained from animal body fluids such as blood (column 3, lines 51-54). Sprenger-Haussels teaches a stabilizing buffer containing a phenol-neutralizing substance and a buffer with an inorganic salt with a salt concentration range of 100 mM to 2.5M (column 2, lines 34-62). Sprenger-Hausells teaches that the phenol-neutralizing substance is preferably 1-30% (wt/vol) PVP-10 (PVP with an average molecular weight of 10,000) (column 3, lines 28-34).
The Agency for Toxic Substances and Disease Registry is drawn to the study of the toxicological profile for phenol and analytical methods for monitoring phenols, its metabolites and other biomarkers of exposure and effect to phenol. Phenol is expected to be present in blood and urine in its free acid and conjugated forms (page 173). The level of phenol detected in blood or urine may not accurately reflect actual phenol exposure because phenol may also appear as a metabolite of benzene or other drugs. It has been shown that under certain acidic conditions used for the hydrolysis of conjugated phenols, acetyl salicylic acid (aspirin) may produce phenol (Baldwin et al. 1981) and yield spuriously higher values for phenol in blood and urine (page 176).
It would have been prima facie obvious to combine Ching, Sprenger-Haussels, and The Agency for Toxic Substances and Disease Registry before the effective filing date of the claimed invention by adding 1-30% (wt/vol) PVP as taught by Sprenger-Haussels to the microbeads slurry containing 0.1M – 6M AS of Ching to arrive at the claimed invention. It would have been prima facie obvious for one of ordinary skill in the art to modify the microbead slurry containing AS of Ching by adding PVP because Sprenger-Haussels teaches that PVP is a phenol-neutralizing substance and can improve the purification of nucleic acids from inhibitory samples and The Agency for Toxic Substances and Disease Registry teaches that phenols may be present in blood both from exposure or as a metabolite from drugs such as aspirin. One of ordinary skill in the art would have a reasonable expectation of success because The Agency for Toxic Substances and Disease Registry teaches that phenols may be present in blood, Sprenger-Haussels teaches that PVP is a phenol-neutralizing compound and that PVP and a high inorganic salt can improve nucleic acid purification from complex samples, and Ching teaches that the inorganic salt, AS, can successfully be used to isolate nucleic acids. It would have been prima facie obvious before the effective filing date that one of ordinary skill in the art would optimize the weight ratio within the ranges taught by Sprenger-Haussels for PVP and Cheng for AS. One of ordinary skill in the art would have a reasonable expectation of success because these are within the ranges for PVP taught by Sprenger-Haussels and AS taught by Ching. In the case where the claimed ranges “overlap or lie inside ranges disclosed by the prior art” a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). (MPEP § 2144.05(I)) Moreover, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. “[W]here 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). (MPEP § 2144.05(II)) “The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages.” In re Peterson, 315 F.3d 1325, 1330, 65 USPQ2d 1379, 1382-83 (Fed. Cir. 2003).
Claim 14 is rejected under 35 U.S.C. 103 as being unpatentable over Ching (US8809519 B2, published 08/19/ 2014, see PTO-892 dated 06/02/2025),Sprenger-Haussels (US7005266 B2, published 02/28/2006, see PTO-892 dated 06/02/2025), and The Agency for Toxic Substances and Disease Registry (https://www.ncbi.nlm.nih.gov/books/NBK599456/, published 09/07/2008, accessed 11/18/2025, see PTO-892) as applied to claim 1 above, and further in view of Fein et al. (US3914187, published October 21, 1975, see PTO-892 dated 06/02/2025).
The combined teachings of Ching, Sprenger-Haussels, and The Agency for Toxic Substances and Disease Registry are discussed above.
The combined teachings of Ching, Sprenger-Haussels, and The Agency for Toxic Substances and Disease Registry do not teach a PVP component that comprises alkylated or halogenated derivatives of polyvinylpyrrolidone.
Fein is drawn to the phenolic complexes of N-alkyl-n-vinylamide polymers for use wherein phenolic materials in limited quantities are desired (abstract). Fein teaches the use of N-vinyl lactams such as N-vinyl-2-pyrrolidone and N-vinyl-substituted derivates such as 3,3-dimethyl-2-pyrrolidone (column 2, lines 45-50) which would meet the limitation of alkylated PVP derivatives.
It would have been prima facie obvious to combine the combined teachings of Ching , Sprenger-Haussels, and The Agency for Toxic Substances and Disease Registry with the teachings of Fein before the effective filing date of the claimed invention by modifying the PVP polymer of Sprenger-Haussels to use the alkylated derivatives of PVP taught be Fein to arrive at the claimed invention. It would have been prima facie obvious for one of ordinary skill in the art to modify the PVP to be an alkylated PVP derivative because Fein teaches that the alkylated PVP derivatives can be used to complex with phenols. One of ordinary skill in the art would have a reasonable expectation of success because Sprenger-Haussels teaches that PVP can be used as a phenol-neutralizing substance and Fein teaches that the alkylated PVP derivatives also complex with phenols.
Response to Arguments
Applicant's arguments filed 02/24/2026 and the Rule 132 declaration signed by Dr. Ralf Wyrich have been fully considered, but they are not persuasive.
Applicant argues that The Agency for Toxic Substances and Diseases Registry (“the Report”) fails to convey to a skilled person that phenol would be found in average blood samples, let alone would present a problem in the analysis of blood samples. Applicant argues that the Report in its entirety describes measuring phenol content within artificial settings and that no one skilled in the art would consider measuring phenol content in artificial studies as relevant to the analysis of blood samples from a real-life individual who are generally unexposed to phenol. Further, applicant argues that the section of the Report cited by the examiner references an article by a 1981 Baldwin publication that within the specific Baldwin publication only discusses urine, not blood. The argument is unpersuasive. The direct teachings of Baldwin were not used in the rejection and therefore any failings of the experimentation or teachings found within Baldwin are not pertinent to the instant rejection. In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). The Report directly teaches that phenols may be found within blood and could possibly be present due to drug metabolism. When combined with the teachings of Sprenger-Haussels that teaches that PVP is a phenol-neutralizing substance and can improve the purification of nucleic acids from inhibitory samples, one of ordinary skill in the art would be motivated to combine the teachings of the Report that phenols could be present in the blood samples with the teachings of Sprenger-Haussels that the phenols may be inhibitory to PCR and could be neutralized by PVP.
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.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SAMANTHA SCHACHERMEYER whose telephone number is (703) 756-5337. The examiner can normally be reached on M-F 9:00 AM – 3:30 PM EST.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Scarlett Goon can be reached on (571) 270-5241. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of an application may be obtained from Patent Center and the Private Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from Patent Center or Private PAIR. Status information for unpublished applications is available through Patent Center and Private PAIR to authorized users only.
Should you have questions about access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free).
/SAMANTHA LYNN SCHACHERMEYER/Examiner, Art Unit 1693 /SCARLETT Y GOON/Supervisory Patent Examiner, Art Unit 1693
Prosecution Insights