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 .
Election/Restrictions
Applicant’s election of Group I in the reply filed on 9/30/2025 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Applicant's election with traverse of bacteria species in the reply filed on 9/30/2025 is acknowledged. The traversal is on the ground(s) that there is no search burden because “search strategies for bacteria, viruses and parasites naturally overlap”. This is not found persuasive because a search, using search terms specifically for bacteria, would not necessarily identify prior art for unrelated pathogens such as viruses or parasites.
The requirement is still deemed proper and is therefore made FINAL.
Status of the Claims
Claim 47 has been withdraw as being directed to a non-elected invention. Claims 26, 34-36, 38, 41 and 53 have been withdrawn as being directed to a non-elected species. Claims 1, 3-8, 10, 13, 16, and 21-23 are under examination at this time.
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 7 and 23 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 7 recites the limitation "pathogenic DNA or RNA" in line 1. There is insufficient antecedent basis for this limitation in the claim.
Claim 23 recites the limitation "the bacterial DNA" in line 2. There is insufficient antecedent basis for this limitation in the claim.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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.
Claim(s) 1, 3-6, 8, 13, 16 and 21-23 are rejected under 35 U.S.C. 103 as being unpatentable over Damgaard et al. (PLoS ONE 10(3): e0120826), and as evidenced by Bosshard et al. (Journal Of Clinical Microbiology, May 2004, 42(5): 2065–2073) and Shahi et al. (Gut Microbes, 2017, 0(0);1-9; https://doi.org/10.1080/19490976.2017. 1349041).
The instant claims are directed to a method of diagnosing a pathogenic infection in a subject, the method comprising
contacting a red blood cell-containing sample from the subject with a reagent capable of detecting a pathogen-associated molecule in the sample, wherein the red blood cell-containing sample is substantially free from all other blood components other than RBCs; and
diagnosing the subject with a pathogenic infection when the pathogen- associated molecule is detected in the sample, wherein the sample is 10 µL or less.
Damgaard et al. teaches a method of detecting bacteria associated with red blood cells (RBCs) and plasma. Damgaard et al. obtained blood from donors and separated the blood into plasma and RBC fractions [the RBC-containing sample is substantially free from all other blook components]. The RBC-fraction was washed twice in sterile phosphate buffered saline (PBS). Samples comprising 0.5 mL of plasma and 0.5 mL washed RBC-suspension were plated out separately under sterile conditions on trypticase soy blood agar (TSA) plates [contacting a RBC-containing sample with a reagent capable of detecting a pathogen-associated molecule], and incubated at 37°C under anaerobic conditions or aerobically in the presence of 5% CO2. Another 0.5 mL of each fraction was handled similarly and incubated on blue lactose plates under aerobic conditions. All plates were examined for colonies after 7 days of incubation. If positive, the number of colonies was counted and the plate was photographed [diagnosing the subject with a pathogenic infection]. Colonies were then individually transferred to fresh plates to obtain monocultures for identification of species. The re-plated colonies were incubated for 4 days (see pages 3-4). Figure 1 of Damgaard et al. shows the frequencies of donors for whom bacteria were found in the RBC-fraction only, in the plasma-fraction only, in both fractions, or in none of the fractions.
Damgaard et al. does not teach that the RBC sample size is 10µL or less. According to section 2144.05 of the MPEP, 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). 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.”)
Here, the general conditions of the claimed method are disclosed by Damgaard et al., and Damgaard et al. was able to detect successfully bacteria in 0.5 mL (500µL) of RBCs. Thus, it is not inventive to discover other optimum or workable sample sizes by routine experimentation. Further, applicant has not demonstrated superior or unexpected results when using a sample size of 10µL or less.
Thus, the invention as a whole was clearly prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention
For claim 3, Damgaard et al. was able to detect successfully bacteria in a RBC-containing sample.
For claims 4-6 and 21-23, Damgaard et al. used colony PCR with primers that target the bacterial 16S rDNA to identify the bacteria (see page 4) [multiple reagents capable of detecting a different pathogen-associated molecule; reagent #1 (TSA plates) detected the presence of whole bacteria; reagent #2 (primers) detected the presence of 16S rDNA]. Damgaard et al. cited Bosshard et al. (2004) for the PCR protocol used to detect the 16S rDNA. As evidenced by Bosshard et al., for PCR, an 800-bp 16S rDNA fragment corresponding to E. coli positions 10 to 806 was amplified with primers. Cycling parameters included an initial denaturation for 5 min at 95°C; 40 cycles of 1 min at 94°C, 1 min at 48°C, and 1 min at 72°C; and a final extension for 10 min at 72°C. Five microliters of the DNA extract was used for amplification in a total volume of 50 μl containing DNA polymerase and the appropriate buffer (see page 2066, left column of Bosshard et al.). When amplifying the same sized fragment from the same region on 16S (base pairs 10 to 806 of 16S) as taught by Bosshard et al., one would also amplify the V4 region. This is evidenced by Shahi et al. Figure 2 of Shahi et al. (see below) shows that the V4 region is included in the 10bp to 806bp fragment amplified by Bosshard et al.
PNG
media_image1.png
328
1086
media_image1.png
Greyscale
For claim 8, Damgaard et al. teaches that infection remains a leading cause of post-transfusion mortality and morbidity. However, bacterial contamination is detected in less than 0.1% of blood units tested (see page 1). Additionally, post-transfusion infection is known to occur at a higher rate than the low frequency of positive findings in conventional bacterial screening systems (see page 4). Lastly, viable bacteria are present in blood from donors who self-reported as medically healthy, indicating that conventional test systems employed by blood banks insufficiently detect bacteria in plasma (see page 2). Thus, in view of the teachings of Damgaard et al. above, it would be obvious for one of ordinary skill in the art to treat a blood donor whose blood was found to test positive for bacteria using the method of Damgaard et al. One would have been motivated to do so and there would have been a reasonable expectation of success given the teachings of Damgaard et al. (infection remains a leading cause of post-transfusion mortality and morbidity; viable bacteria are present in blood from donors who self-reported as medically healthy, indicating that conventional test systems employed by blood banks insufficiently detect bacteria in plasma).
For claim 13, Damgaard et al. used 500µL of an RBC fraction. Damgaard et al. does not state the number of RBCs in the sample. However, Damgaard et al. was able to detect successfully bacteria in 500µL of RBCs.
According to section 2144.05 of the MPEP, 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). 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.”)
Here, the general conditions of the claimed method are disclosed by Damgaard et al., and Damgaard et al. was able to detect successfully bacteria in 0.5 mL (500µL) of RBCs. Thus, it is not inventive to discover other optimum or workable sample sizes (amount of RBCs) by routine experimentation. Further, applicant has not demonstrated superior or unexpected results when using a sample size of at least 1 million RBCs.
For claim 16, Damgaard et al. teaches that infectious complications to blood transfusion include sepsis, pneumonia, abscesses, wound infection, meningitis, hemolysis, empyema, urine tract infection and fever. Such infections may be partly accounted for by an inhibitory effect of the transfusion per se on the immune system. However, another cause might be unrecognized bacterial contamination of the transfused blood units (see page 2). Thus, for donors who self-report as healthy and/or who are suspected as having a bacterial infection (e.g., sepsis), it would be obvious to perform the method of Damgaard et al. on such subjects to detect the presence of bacteria prior to a blood donation.
Claim 10 is rejected under 35 U.S.C. 103 as being unpatentable over Damgaard et al. (PLoS ONE, 2015, 10(3): e0120826), Bosshard et al. (Journal Of Clinical Microbiology, May 2004, 42(5): 2065–2073) and Shahi et al. (Gut Microbes, 2017, 0(0);1-9; https://doi.org/10.1080/19490976.2017. 1349041) as applied to claims 1, 3-6, 8, 13, 16 and 21-23 above, and further in view of Carmen et al. (U.S. Patent No. 4915848; published 4/10/1990).
The instant claims are directed to the method of claim 1 where the method further comprises filtering the blood sample to remove non-RBC blood cells.
The teachings of Damgaard et al., Bosshard et al. and Shahi et al. are outline above and incorporated herein. Damgaard et al., Bosshard et al. and Shahi et al. do not teach filtering the blood sample. However, Carmen et al. teaches a method of processing whole blood to obtain RBCs substantially free of white blood cells. The method comprises:
(a) collecting whole blood from a donor into a donor bag of a closed multiple blood bag system comprising a donor bag in communication with at least one other bag via connecting tubing, the tubing including an integral white blood cell filter consisting essentially of a single continuous filtering fiber of about 2.2 denier and the at least one other bag including a red blood cell additive solution;
(b) centrifuging the whole blood in the donor bag under conditions sufficient to separate the whole blood into an upper plasma component and a lower red blood cell component which includes some white blood cells;
(c) removing the plasma component from the donor bag;
(d) introducing the additive solution into the donor bag by passing the solution through the filter to prime the filter removing air from the filter and then mixing the solution with the red and white blood cells; and
(e) passing the mixture of step (d) through the filter and into the at least one other bag under conditions sufficient to remove substantially all white blood cells from the mixture, thereby providing a red blood cell preparation substantially free of white blood cells and suitable for long term storage without substantial amounts of white blood cell contaminants.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to use methods known in the art to separate RBCs from non-RBC blood cells prior to performing the method of Damgaard et al. One would have been motivated to do in order to obtain a RBC sample that is substantially free from other blood components. There would have been a reasonable expectation of success given the teachings outlined in Carmen et al. (see the Examples).
Thus, the invention as a whole was clearly prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Nicole Kinsey White whose telephone number is (571)272-9943. The examiner can normally be reached M to Th 6:30 am to 6:00 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, Thomas Visone can be reached at 571-270-0684. 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.
/NICOLE KINSEY WHITE/Primary Examiner, Art Unit 1672