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
Applicant’s amendment filed on 21 May 2026 is entered. Claims 10-19 are cancelled. Claims 1-9 and 20-21 are pending and under examination.
Priority and Domestic Benefit
Applicant’s claim for priority to the filing date of PCT/US2022/038792 filed 29 July 2022, and Applicant’s claim to the domestic benefit of US Provisional Application no. 63/227,717 is acknowledged. Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55. The effective filing date is 30 July 2021.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 29 January 2024 and 07 November 2025 is being considered by the examiner.
Election/Restrictions
Applicant’s election without traverse of Group I, claims 1-9 and 20-21, in the reply filed on 21 May 2026 is acknowledged.
Claim Objections
Claim 7 is objected to because of the following informalities:
Claim 7 recites the contacting comprises “contact the biological sample with the anticoagulant and the aggregating agent simultaneously”. The word “contact” is conjugated incorrectly, and should be corrected to “wherein the aggregation agent and the anticoagulant are simultaneously contacted with the biological sample”.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1-9 and 20-21 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 and 20 recite the limitation "a second volume of suspension solution" in line 11 of claim 1 and in line 6 of claim 20. Claims 1 and 20 do not recite a first volume of suspension solution anywhere in the method. It is unclear whether the non-recited “first volume of suspension solution” is required, or what it comprises. Claim 1 is further confusing as it recites “a sedimentation solution having a first volume” in line 4 and further recites “the second volume being smaller than the first volume” in the last line. It is uncertain whether the “second volume of suspension solution” is compared with and smaller than “the first volume of sedimentation solution”.
Claim 2 recites the method of claim 1 comprising loading the sample solution in a microfluidic analysis device. It is unclear if this method step in claim 2 is to be performed in addition to those steps recited in claim 1, or if claim 2 recites a method step to replace the method steps of claim 1.
Claims 3, 4, and 9 have the same issue, where claim 3 recites a new step of using the microfluidic analysis device to perform an antimicrobial susceptibility test, claim 4 recites a new step of using the microfluidic analysis device to identify one or more pathogens in the sample solution, and claim 9 recites a new step of washing the separated pellet prior to loading the sample solution into the microfluidic analysis device. It is unclear if these new steps are to be performed in addition to those steps recited in claim 1, or if these new steps are intended to replace the method steps of claim 1.
Claims 3, 4, and 9 recite the limitation " microfluidic analysis device " in line 1 of claims 3 and 4 and line 2 of claim 9. There is insufficient antecedent basis for this limitation in the claims.
Claims 2-9 depend on claim 1, and claim 21 depends on claim 20, so they are indefinite for the same reasons.
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 1-7, 9, and 20-21 are rejected under 35 U.S.C. 103 as being unpatentable over Karp et al. (US 20170153223 A1, 01 June 2017) in view of Croxatto et al. (Preparation of a Blood Culture Pellet for Rapid Bacterial Identification and Antibiotic Susceptibility Testing. J. Vis. Exp. 2014 (92), e51985, doi:10.3791/51985).
Regarding claims 1, 2, 5, 7, and 20-21, Karp teaches a method of removing red blood cells (RBCs) from a blood sample using a sedimentation procedure (Karp [0007]). The separation aspect assists in separating erythrocytes (red blood cells) from other cells in blood, such as by aggregation of the red blood cells. A suitable aggregation device or device component uses chambers with at least one small dimension (e.g., a microfluidic chip) to control the interaction of the blood with a solution containing a high molecular weight polymer (e.g., dextran) to achieve separation (Abstract). Karp teaches the blood sample is mixed with a sedimenting solution comprising an aggregating high-molecular weight polysaccharide, such as dextran (Karp [0007]) as well as an anticoagulant before performing the sedimentation procedure (Karp [0055]). Karp teaches that the RBCs are aggregated and sedimented into the lower layer comprising the sedimenting solution, leaving behind a top layer blood sample that is devoid of RBCs and contains the desired cell (Karp [0007]), which may then be processed to isolate bacteria of interest (Karp [0047]). Karp teaches that all of these procedures are carried out in a microfluidic device (Karp Abstract, [0007]-[0010]).
Karp does not teach centrifuging the collected RBC separated blood sample (reads on top layer) to form a pellet, separating the pellet from a supernatant, or resuspending the pellet into a suspension solution.
Croxatto teaches a method of preparing a bacterial pellet from a blood culture by centrifuging the sample, removing the supernatant, and resuspending the bacterial pellet in a suspension solution (pg. 2 Protocol 1.2 “Preparation of a blood culture bacterial pellet by lysis centrifugation”).
It would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date of the present invention to modify Karp’s method of isolating a bacterial cell of interest from their gravimetric sedimented RBC separated blood sample by performing Croxatto’s centrifuging protocol on Karp’s RBC separated blood sample, in order to pellet the bacteria within Karp’s RBC separated blood sample, and resuspend the pellet in a new suspension for further analysis. One of ordinary skill in the art would have been motivated to do so with a reasonable expectation of success because Karp teaches that their top layer blood sample that is devoid of RBCs may be processed to isolate bacteria of interest (Karp [0047]), and Croxatto teaches a centrifugation method that is suitable to isolate a bacteria of interest from a blood sample. Thus, when the teachings of Karp and Croxatto are combined, one of ordinary skill in the art would reasonably expect Croxatto’s centrifugation method to isolate the bacteria within Karp’s RBC separated blood sample.
Regarding claim 3-4, Croxatto teaches a method of performing an antimicrobial susceptibility test and bacterial pathogen identification procedure inside an automated microbial system that is performed after the bacteria are isolated from the blood sample (Croxatto pgs. 2-3 Protocol 3).
Regarding claim 6, Karp teaches the dextran aggregating solution may have 1-10% dextran concentration (Karp [0034]).
Regarding claim 9, Croxatto teaches a method step of resuspending the bacterial pellet in sterile, distilled water to wash the bacterial pellet (Croxatto pg. 2 Protocol 1.2 “Preparation of a blood culture bacterial pellet by lysis centrifugation” step 4).
Claim 8 is rejected under 35 U.S.C. 103 as being unpatentable over Karp and Croxatto as applied to claims 1-7, 9, and 20-21 above, and further in view of Lewis et al. (Argatroban Anticoagulant Therapy in Patients With Heparin-Induced Thrombocytopenia, Circulation, Volume 103, Issue 14, 10 April 2001; Pages 1838-1843).
Karp teaches that the dextran in the solution has a molecular weight of 500-1,000 kDa [0034].
However, Karp and Croxatto do not teach the anticoagulant is argatroban.
Lewis teaches the anticoagulant, argatroban, and its anticoagulant properties in the context of blood samples (Lewis Title and Abstract).
It would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date of the present invention to substitute Lewis’ argatroban for the anticoagulant in Karp’s sedimenting solution. One of ordinary skill in the art would have been motivated to do so with a reasonable expectation of success because argatroban was understood in the art to be an anticoagulant, especially in the context of blood and blood samples, and Karp taught that their blood sample sedimenting solution may comprise an anticoagulant. In light of Karp and Lewis’ teachings, one of ordinary skill in the art would therefore understand that Lewis’ argatroban would be a suitable anticoagulant for use in Karp’s blood sample sedimenting solution.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ALEXANDER M DURYEE whose telephone number is (571)272-9377. The examiner can normally be reached Monday - Friday 9:00 am - 5:00 pm.
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.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Louise Humphrey can be reached on (571)-272-5543. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/Alexander M Duryee/Examiner, Art Unit 1657 /LOUISE W HUMPHREY/Supervisory Patent Examiner, Art Unit 1657