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
Election/Restrictions
1. Applicant's election of Group II, claims 8-17, with traverse, filed July 20, 2026 is acknowledged and has been entered. Claims 1-7 and 18-20 are withdrawn from further consideration by the examiner, 37 CFR 1.142(b), as being claims drawn to a non-elected invention. Accordingly, claims 1-20 are pending. Claims 8-17 are under examination.
2. Applicant traverses the restriction requirement on the grounds that XXX.
Applicant’s argument is not persuasive because XXX.
Priority
3. Receipt is acknowledged of certified copies of foreign priority papers required by 37 CFR 1.55, which papers have been placed of record in the file.
4. Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. Acknowledgment is also made of Applicant’s claim for foreign priority under 35 U.S.C. 119(b) or 365(b), and 37 CFR 1.55 on the basis of the filing date of CHINA 2022108196382 filed 07/13/2022. This application is a continuation-in-part of U.S. Application Serial Number 18/304,915 filed 04/21/2023, which claims the benefit of priority of foreign application CHINA 2022108196382 filed 07/13/2022. Based on the filing receipt, the effective filing date of this application is July 13, 2022 which is the filing date of Foreign Application CHINA 2022108196382 from which the benefit of foreign priority is claimed.
Claim Objections
5. Claim 8, step (2) is objected to in reciting “using an eluent solution to eluent the markers.” It should recite “using an eluent solution to elute the markers.” Appropriate correction is required.
6. Claim 9 is objected to in reciting “blood sample is treated by the magnetic bead.” It should recite “blood sample is treated with the magnetic bead.” Appropriate correction is required.
7. Claim 11 is objected to in reciting “the magnetic bead that is treated by an activating agent.” It should recite “the magnetic bead that is treated with an activating agent.” Appropriate correction is required.
8. Claim 14 is objected to in reciting “with1%.” It should recite “with 1%.” Appropriate correction is required.
9. Claim 17 is objected to in reciting “with5%.” It should recite “with 5%.” Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
10. Claims 8-17 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.
Claim 8, step (2) recites “using an eluent solution to eluent the markers from the magnetic beads;” however, the claim is indefinite because it recites intended use of an eluent solution but fails to clearly define what method/process steps are being encompassed. A claim is indefinite where it merely recites use without any active, positive steps... delimiting how this use is actually practiced.
Claim 8, step (2) also recites “using a liquid chromatography tandem-mass spectrometry;” however, the claim is indefinite because it recites intended use of liquid chromatography tandem-mass spectrometry but fails to clearly define what method/process steps are being encompassed. A claim is indefinite where it merely recites use without any active, positive steps... delimiting how this use is actually practiced.
Claim 8 is vague and indefinite in reciting, “to test the numbers of the markers in the blood sample” because “test” and “numbers” appear to be subjective terms lacking a comparative basis for defining their metes and bounds. Does Applicant perhaps intend “to measure or quantitatively determine the amount or concentration of each of the markers in the blood sample?”
Claim 9 is ambiguous in reciting “buffer formation solution” because it is unclear what is encompassed in the term “formation” relative to the “buffer solution.” See also claim 10.
Claim 9 is indefinite in reciting, “PMSF”. Acronyms or abbreviations should be fully defined and recited at least one time in a given set of claims.
Claim 9 is also indefinite in using parenthetical symbols in reciting “(PMSF)” because it is unclear whether the limitation within the parenthesis is a part of the claimed invention.
Claim 9 is confusing in reciting “wherein the step (1) is as follows: the blood sample firstly needs to be incubated in a buffer formation solution with an angiotensin converting enzyme inhibitor (PMSF) under acidic conditions” because “step (1)” as recited in claim 8 and “firstly” in the instant claim which refers back to step (1) in claim 8 appear to overlap in a contradictory manner. Perhaps Applicant intends “wherein the blood sample in step (1) is pre-treated with a buffer solution containing an angiotensin converting enzyme inhibitor and incubated under acidic conditions.”
Claim 9 lacks clear antecedent basis in reciting “the end of the incubation.”
Claim 9 is further confusing in reciting “at the end of the incubation, a stop buffer is added to stop the incubation” because “end of the incubation” and “stop the incubation” appear to be synonymous and redundant in nature. As such, it is unclear what Applicant intends to encompass differentially between the two consonant recitations. In particular, the recitation fails to clearly define what parametric requirement, i.e. incubation time frame, visible product formation, encompasses the “end of the incubation” so as to be distinct from the addition of a stop buffer. The recitation further fails to clearly define what is encompassed in “stop the incubation” because the stop buffer appears to stop the buffer activity of the angiotensin converting enzyme inhibitor contained in the buffer solution under acidic conditions.
Claim 11 is vague and indefinite in lacking clear antecedent basis in relation to claim 8 from which the instant claim ultimately depends in reciting “the step (1) further comprises: adsorbing the blood sample with the magnetic bead that is treated with an activating agent” because the blood sample in claim 8 is treated with a magnetic bead bonded with balanced hydrophilic-lipophilic polymer absent an activating agent. Accordingly, it is unclear where in the method steps recited in claim 8 the magnetic bead would have been treated with this activating agent, in question. See also claim 12.
Claim 11 is also indefinite in lacking clear antecedent basis relative to claim 8 from which the instant claim depends in reciting “adsorbing the blood sample with the magnetic bead that is treated with an activating agent and a balanced solution” because it is unclear what essential structural and/or functional cooperative relationship exists between the instant “balanced solution” and the components recited in claim 8, step (1) including the “balanced hydrophilic-lipophilic polymer.” Should the magnetic bead bonded with the balanced hydrophilic-lipophilic polymer used in treating the blood sample in claim 8, step (1) be in the balanced solution? See also claim 14.
Claim 17 lacks antecedent basis in reciting “the liquid chromatogram mobile phase in the step (2).”
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
11. Claim 8 is rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by Goethel et al. (US 2017/0138940 A1).
Goethel et al. disclose a method for detecting and isolating markers (target biomarkers, trace components) in a blood sample (Abstract; [0006, 0008, 0009]). The method comprises (1) treating the blood sample with a magnetic silica gel beads having a balanced hydrophilic-lipophilic polymer bonded on its surface to absorb the markers (biomarker targets) in the blood sample. The hydrophilic polymer portion is formed from ionic and polar solvents having charged functional groups including carboxyl COOH, and amino NH2. The lipophilic polymer portion is formed from aprotic nonpolar solvents such as hexane which is highly lipophilic [0021, 0030, 0032, 0037, 0055]. Goethel et al. teach that the markers are aldosterone, angiotensin I, angiotensin II, cortisol, 18-hydrocorticosterone (deoxycorticosterone), and 18-Hydroxy Cortisol (pregnenolone) [0021, 0030, 0049, 0054]. The method further comprises (2) using an eluent solution (organic polar solvents: ethanol, methanol, isopropanol, PEG) to elute the markers from the magnetic bead; and using a liquid chromatography tandem-mass spectrometry (LC-MS-MS) to test the numbers (isolate and quantify) of the markers in the blood sample [0021, 0022, 0034-0036, 0073-0080].
Goethel et al. teach that the magnetic bead is pretreated with an activating agent which is 50% ethanol in a balanced solution and then washed with a washing liquid. The balanced solution is an aqueous solution with 1% formic acid (carboxylic acid). The magnetic bead is a magnetic granule having a core-shell solid phase, a granularity of 30-50 µm (encompassed within 50 nm to 110 µm), a specific surface area of 600 m2/g, and a pore diameter of 80A are all encompassed within the parameters as taught by Goethel et al. [0032-0034, 0058-0066]. Accordingly, Goethel et al. appears to read on Applicant’s claimed invention.
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.
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.
12. Claims 9-17 are rejected under 35 U.S.C. 103 as being unpatentable over Goethel et al. (US 2017/0138940) in view of ZHUO et al. (CN114354806).
Goethel et al. is discussed supra. Goethel et al. differ from the instant invention in failing to teach pretreating the blood sample with angiotensin converting enzyme inhibitor.
However, Zhuo et al. discloses a human plasma rennin activity LC-MS detection method which comprises preparing a buffer system, incubating the plasma sample in the buffer system containing angiotensin converting enzyme inhibitor under acidic conditions, and then quantitatively detecting the amount of angiotensin I using LC-MS (Abstract translation).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the instant invention to have incorporate the angiotensin converting enzyme inhibitor as taught by Zhuo into the method of detecting the biomarkers including angiotensin I as taught by Goethel because Zhuo taught that the angiotensin converting enzyme inhibitor prevents the formation of angiotensin II for accurate detection of angiotensin I.
As to the recitations of the eluent solution containing 50% methanol; the washing liquid 1 containing 10% methanol; the mobile phase B containing 5% isopropanol, and 1 mM ammonium fluoride; generally, differences in concentrations or temperatures 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) (Claimed process which was performed at a temperature between 40°C and 80°C and an acid concentration between 25% and 70% was held to be prima facie obvious over a reference process which differed from the claims only in that the reference process was performed at a temperature of 100°C and an acid concentration of 10%.); see also Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382 ("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 Hoeschele, 406 F.2d 1403, 160 USPQ 809 (CCPA 1969) (Claimed elastomeric polyurethanes which fell within the broad scope of the references were held to be unpatentable thereover because, among other reasons, there was no evidence of the criticality of the claimed ranges of molecular weight or molar proportions.). For more recent cases applying this principle, see Merck & Co. Inc. v. Biocraft Lab. Inc., 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir.), cert. denied, 493 U.S. 975 (1989); In re Kulling, 897 F.2d 1147, 14 USPQ2d 1056 (Fed. Cir. 1990); and In re Geisler, 116 F.3d 1465, 43 USPQ2d 1362 (Fed. Cir. 1997); Smith v. Nichols, 88 U.S. 112, 118-19 (1874) (a change in form, proportions, or degree "will not sustain a patent"); In re Williams, 36 F.2d 436, 438 (CCPA 1929) ("It is a settled principle of law that a mere carrying forward of an original patented conception involving only change of form, proportions, or degree, or the substitution of equivalents doing the same thing as the original invention, by substantially the same means, is not such an invention as will sustain a patent, even though the changes of the kind may produce better results than prior inventions."). See also KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 416 (2007) (identifying "the need for caution in granting a patent based on the combination of elements found in the prior art."). Since Applicant has not disclosed that the specific limitations recited in instant claims 12 and 14-17 are for any particular purpose or solve any stated problem and the prior art teaches that reagent parameters often vary according to the sample being analyzed and various matrices, solutions and parameters appear to work equally as well; absent unexpected results, it would have been obvious for one of ordinary skill to discover the optimum workable ranges of the methods disclosed by the prior art by normal optimization procedures.
13. No claims are allowed.
Remarks
14. Prior art made of record are not relied upon but considered pertinent to the applicants' disclosure:
Any inquiry concerning this communication or earlier communications from the examiner should be directed to GAILENE R. GABEL whose telephone number is (571)272-0820. The examiner can normally be reached Monday, Tuesday, and Thursday 5:30 AM to 4:00 PM.
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/GAILENE GABEL/Primary Examiner, Art Unit 1678
August 7, 2026
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