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 .
Priority
The present application was filed 02/27/2023. This application is a continuation of application 17/607,978, filed 11/01/2021, which is a proper National Stage (371) entry of PCT Application No. PCT/US2020/030947, filed 05/01/2020, which claims benefit to provisional application 62/842,094, filed 05/02/2019.
Status of the Claims
Claims 1-3, 7, 20, 22, 34, 36-40, 42, 44, and 48 are currently pending and examined below. Claims 4-6, 8-19, 21, 23-33 , 35, 41, 43, 45-47, and 49 are cancelled.
Information Disclosure Statement
The information disclosure statement (IDS) filed 09/23/2024 has been considered, initialed, and is attached hereto.
Specification
The disclosure is further objected to because of the following informalities:
On pages 2-45 of the specification the end of the first and second line of text is illegible, specifically the last words of said one to two lines are not visible on any pages of the specification.
Appropriate correction is required.
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.
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.
Claims 1-3, 7, 20, 22, 34, 36-40, 42, 44, and 48 are rejected under 35 U.S.C. 103 as being unpatentable over Bennani et al. US20150330979A1 in view of Wachi et al. Studies on preliminary concentration methods for recovery of fetal nucleated red blood cells in maternal blood. Congenital anomalies. 2004 Dec;44(4):196-203 (of record, IDS 09/23/2024).
Regarding claim 1, Bennani teaches a method for enrichment and isolation of fetal nucleated red blood cells (Bennani, page 2, paragraph [0012], lines 1-3). Bennani further teaches that the method is carried out in a biological samples such as maternal blood or a fetal nucleated red blood cell enriched cell fraction of maternal blood (Bennani, page 2, paragraph [0013], lines 2-5). Bennani further teaches that the positive selection methods typically include one or more positive immunoselection based steps which can be used in conjunction with one or more other methods that deplete other cell types, e.g. maternal lymphocytes or red blood cells and that such methods include negative selection and cell density separation techniques (Bennani, page 2, see entire paragraph [0014]). Bennani further teaches that to improve enrichment for fetal nucleated red blood cells, a pre-enrichment process, such as density separation, can be used, prior to positive selection (Bennani, page 3, see entire paragraph [0022]). Bennani further teaches that the positive immunoselection typically comprises contacting the biological sample with one or more positive immunoselective antibodies wherein the positive immunoselective antibody selectively binds to fetal nucleated red blood cells relative to one or more other cells types in the sample and selecting cells bound to said positive immunoselective antibodies (Bennani, page 2, paragraph [0017], line 6 -page 3, line 1). Bennani further teaches that multiple positive selection processes can be used, e.g. positive selection using magnetic activated cell sorting followed by positive selection using fluorescence activated cell sorting (Bennani, page 3, paragraph [0018], lines 10-12). Bennani further teaches that following positive selection, fetal nucleated red blood cells can be isolated by a physical technique such as micromanipulation (Bennani, page 10, see entire paragraph [0113]) and that micromanipulation may select or isolate a single or multiple fetal nucleated red blood cells (Bennani, page 10, paragraph [0114], lines 7-8).
Bennani fails to teach that the pre-enrichment process comprises using a filter that retains fetal nucleated red blood cell and allows non-nucleated red blood cells to pass through the filter to obtain a fetal nucleated red blood cell containing cell fraction.
Wachi teaches a molecular filter method for preliminary concentration of fetal nucleated red blood cells in maternal peripheral blood (Wachi, page 196, ‘Abstract’, lines 9-13). Wachi further teaches that when samples pass through the filters the anucleated red blood cells pass through the filter and nucleated red blood cells are trapped on the filter (Wachi, page 197, ‘Basic study of high molecular filters’, lines 7-10). Wachi further teaches that compared with the Ficoll centrifugation method (density gradient method, see page 197, 2nd paragraph, lines 8-9) the filter method showed a significantly higher recovery rate, indicating its superiority as a preliminary concentration step (Wachi, page 202, lines 4-8). Wachi further teaches that successful prenatal diagnosis with fetal cells recovered from maternal blood depends on the recovery of sufficient fetal cells (Wachi, page 197, ‘Materials and Methods’, lines 4-6).
It would have been prima facie obvious to one having ordinary skill in the art at the time the claimed invention was effectively filed to have applied to the invention of Bennani, which includes using a preselection step that deletes other cell types, the preselection method of Wachi of using a filter that retains fetal nucleated red blood cells while letting anucleated red blood cells pass through, because of the teaching of Wachi that this method is superior to the density gradient as taught by Bennani. One of ordinary skill in the art would be motivated to do so because of the teaching of Wachi that successful prenatal diagnosis relies on sufficient recovery of fetal cells.
Regarding claim 2, Bennani teaches selecting fetal nucleated red blood cells using the monoclonal antibody 4B9 (Bennani, page 7, paragraph [0085], lines 1-2).
Regarding claims 3 and 7, Bennani and the cited art above as applied to claim 2 also applies to claims 3 and 7.
Wachi teaches that the filter that trapped nucleated cells is washed with a reverse flow of 50 ml of phosphate buffered saline (PBS) and that the nucleated red blood cells are recovered from the collected washings (Wachi, page 198, lines 1-6).
Regarding claim 20, Bennani teaches positive selection markers comprising DC-Ruby and DAPI (Bennani, page 7, paragraph [0081] and [0084]).
Regarding claim 22¸ Bennani teaches that the antibodies and nuclear stains used can be modified to permit selection and separation of the fetal nucleated red blood cells and that the modified antibodies can comprise a fluorescent moiety (Bennani, page 8, paragraph [0094], lines 1-8).
Regarding claim 34, Bennani teaches obtaining the cells from maternal blood between about 6 weeks and 20 weeks gestation (Bennani, page 11, paragraph [0117], lines 1-4).
Regarding claims 36 and 37, Bennani teaches that the isolation techniques permit enrichment (claim 37) and isolation (claim 36) of fetal nucleated red blood cells from a mixed cell population (Bennani, page 2, paragraph [0012], lines 1-4).
Regarding claim 38, Bennani teaches that chromosomal abnormalities are detectable using the chromosomes or nucleic acid from lysed fetal nucleated red blood cells by methods including fluorescence in situ hybridization, polymerase chain reaction and others (Bennani, page 11, paragraph [0125], lines 1-7).
Regarding claim 39, Bennani teaches that abnormalities are detectable using the chromosomes or nucleic acid from lysed fetal nucleated red blood cells produced by the methods of the present disclosure (Bennani, page 11, paragraph [0125], lines 1-5).
Regarding claims 40 and 42, Bennani teaches that single cells or groups of two to four or more cells can be amplified to provide sufficient nucleic acid for analysis and groups of cells of 5 or more can be analyzed without amplification (Bennani, page 11, paragraph [0124], lines 1-6).
Regarding claim 44, Bennani teaches that abnormalities are detectable using quantitative polymerase chain reaction (Bennani, page 11, paragraph [0125], lines 1-11).
Regarding claim 48, Bennani teaches that genetic fingerprinting methods involving Short Tandem Repeat analysis or single nucleotide polymorphism analysis can be used to validate the identity of fetal nucleated red blood cells (Bennani, page 10, see entire paragraph [0121]).
Communication
Any inquiry concerning this communication or earlier communications from the examiner should be directed to STEFANIE J KIRWIN whose telephone number is (571)272-6574. The examiner can normally be reached Monday - Thursday 10 am - 3.30 pm.
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/STEFANIE J. KIRWIN/Examiner, Art Unit 1677
/Soren Harward/Primary Examiner, TC 1600
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