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 .
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 Claims 26, 34-36, 38, 41 and 53 have been withdrawn as being directed to a non-elected species.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, 3-5, 7-8, 10, 13, 16, 21-22 and 54 are under examination at this time.
Withdrawn Rejections
The rejection of claims 7 and 23 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, has been withdrawn in view of applicant’s amendments to claim 7 and the cancelation of claim 23.
The rejection of claims 1, 3-6, 8, 13, 16 and 21-23 under 35 U.S.C. 103 as being unpatentable over Damgaard et al. (PLoS ONE 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 (Gut Microbes, 2017, 0(0);1-9; https://doi.org/10.1080/19490976.2017. 1349041) has been withdrawn in view of applicant’s amendments to claim 1.
The rejection of claim 10 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), Shahi et al. (Gut Microbes, 2017, 0(0);1-9; https://doi.org/10.1080/19490976.2017. 1349041) and Carmen et al. (U.S. Patent No. 4915848; published 4/10/1990) has been withdrawn in view of applicant’s amendments to claim 1.
New Rejections Necessitated by Amendment
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, 3-5, 7-8, 10, 13, 16, 21-22 and 54 are rejected under 35 U.S.C. 103 as being unpatentable over Van Bruggen et al. (AU 2016212815; published 8/17/2027) and as evidenced by Bosshard et al. (Journal Of Clinical Microbiology, May 2004, 42(5): 2065–2073; previously cited) and Shahi et al. (Gut Microbes, 2017, 0(0);1-9; https://doi.org/10.1080/19490976.2017. 1349041; previously cited).
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 red blood cells (RBCs);
wherein the pathogen-associated molecule is DNA or RNA; and
diagnosing the subject with a pathogenic infection when the reagent detects the pathogen- associated molecule in the sample, wherein the sample is 10 µL or less.
Van Bruggen et al. teaches that for the isolation of RBCs that have bound at least one pathogen, preferably beads, such as magnetic beads, or a filter comprising a non-specific RBC adhesion molecule binder are used. For instance, if magnetic beads are used, following binding of RBCs bound by at least one pathogen to the beads, these complexes are isolated from the blood or blood product sample by pulling them to a magnet. The supernatant can subsequently be discarded, thereby obtaining isolated beads bound by RBCs that have bound at least one pathogen [wherein the red blood cell-containing sample is substantially free from all other blood components other than red blood cells (RBCs)].
Van Bruggen et al. further teaches a method for isolating and/or enriching pathogens from a sample of blood or of a blood product comprising red blood cells (RBCs), the method comprising:
i) contacting said sample with a support comprising a non-specific RBC adhesion molecule binder to allow binding of RBCs that have bound at least one pathogen to said binder; and
ii) isolating RBCs that are bound to said support from said sample, preferably by removing cells and other components in said sample that have not bound to said binder [wherein the red blood cell-containing sample is substantially free from all other blood components other than red blood cells (RBCs)].
Detecting the presence of RBCs that have bound at least one pathogen can be performed using any methods known for detecting RBCs and pathogens in the art. Preferred methods include microscopy, including confocal microscopy and/or fluorescent microscopy, and cytometry, including the use of a haemocytometer and flow cytometry. For the detection of pathogens, without necessarily identifying the pathogen, general pathogen or general bacteria, virus, parasite, etc. label can used. Such general pathogen detection methods are generally known in the art. Preferred, but not limiting examples, are DNA labelling, polymerase chain reaction (PCR) using pathogen non-specific consensus primers, and, pan genera detection (PGD) labels, the latter preferably if the pathogens are bacteria [contacting a red blood cell-containing sample from the subject with a reagent capable of detecting a pathogen-associated molecule in the sample]. Because RBCs do not contain DNA, detection of DNA associated with RBCs indicates that the RBCs have bound at least one pathogen [wherein the pathogen-associated molecule is DNA or RNA; diagnosing the subject with a pathogenic infection when the reagent detects the pathogen- associated molecule in the sample]. Bacterial and fungal nucleic acids can be amplified nonspecifically by PCR using consensus primers. For instance, fungal DNA can be detected by means of PCR by amplifying a region of the 18 ssu rRNA. Bacterial DNA can for instance be detected using consensus primers which bind to the highly conserved 16S or 23S regions of the rRNA (see page 22, line 4 to page 23, line 31).
Van Bruggen 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 Van Bruggen et al., and Van Bruggen et al. was able to detect successfully bacteria in a sample 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.
For claim 3, Van Bruggen et al. was able to detect successfully bacteria in a RBC-containing sample (see the Examples).
For claims 4-5 and 21, Van Bruggen et al. teaches pathogen detection methods include i) microscopy, including confocal microscopy and/or fluorescent microscopy, and cytometry, including the use of a haemocytometer and flow cytometry, and ii) DNA labelling, polymerase chain reaction (PCR) using pathogen non-specific consensus primers, and, pan genera detection (PGD) labels. Additionally, Van Bruggen et al. teaches that bacterial DNA can be detected using consensus primers which bind to the highly conserved 16S or 23S regions of the rDNA [multiple reagents capable of detecting a different pathogen-associated molecule].
For claims 7, 8 and 16, Van Bruggen et al. teaches that the methods for detecting pathogens and/or identifying said pathogens according to the invention are particularly suitable for rapid diagnosis of sepsis. The present inventors have further found that pathogens in blood can already be detected using the methods of the invention two days before a positive blood culture can be obtained. Van Bruggen et al. further teaches that the methods of the invention allow for early detection of the presence of pathogens in the blood, for the early detection of sepsis, for prediction of the development of sepsis and for identification of sepsis-causing pathogens in blood (see page 27, lines 17-24). Thus, the method taught by Van Bruggen et al. can be used on a patient who has been diagnosed with an infection (e.g., sepsis), or who is suspected of having sepsis, or who is culture negative.
For claim 10, Van Bruggen et al. teaches that a first component comprising RBCs is preferably contacted with a filter by flowing the component and/or RBCs through and/or along the filter. That way, RBCs that have bound at least one pathogen are adsorbed onto the material of the filter, i.e. the non-specific RBC adhesion molecule binder. RBCs that have not bound at least one pathogen, are not adsorbed to the filter material but flow through and/or along the filter (see page 17, lines 9-21 and page 22, lines 2-14).
For claim 13, Van Bruggen et al. does not teach that the RBC sample contains at least 1 million RBC. 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 Van Bruggen et al., and Van Bruggen et al. was able to detect successfully bacteria DNA or RNA in a sample of RBCs. Thus, it is not inventive to discover other optimum or workable amounts of RBCs by routine experimentation. Further, applicant has not demonstrated superior or unexpected results when using a sample containing at least 1 million RBCs.
For claim 22, Bosshard et al. teaches to identify bacteria, one can amplify an 800-bp fragment of the16S rDNA. The 800-bp fragment, which corresponds to E. coli positions 10 to 806, was amplified with primers (see page 2066, left column of Bosshard et al.). When amplifying this fragment 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 10 to 806bp fragment amplified by Bosshard et al.
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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.
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.
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.
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/NICOLE KINSEY WHITE/Primary Examiner, Art Unit 1672
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