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
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on May 19, 2026 has been entered.
Amendment Entry
2. Applicant's amendment / response filed May 19, 2026 is acknowledged and has been entered. Claims 278, 288, 300, 308, and 309 have been amended. Claim 287 has been cancelled. Claims 316 and 317 have been added. Claims 300-315 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention and species, there being no allowable generic or linking claim. Accordingly, claims 278-286, 288-290 and 292-317 are pending. Claims 278-286, 288-290, 292-299, 316 and 317 are under examination.
Withdrawn Rejections / Objections
3. Any objection or rejection not reiterated herein, has been withdrawn.
4. The rejections of claim 287 are moot in light of Applicant's cancellation of the claims.
5. In light of Applicant’s amendment and arguments, the rejection of claims 278-281, 283, 290, 293-296, and 299 under 35 U.S.C. 102(a)(1) as being anticipate by Hatt et al. (Prenatal Diagnosis 34: 1-7 (2014)), is hereby, withdrawn.
6. In light of Applicant’s amendment and arguments, the rejection of claims 278-283, 290, and 292-299 under 35 U.S.C. 102(a)(1) as being anticipate by Eckelt et al. (US 2013/0331284) in light of Hatt et al. (Prenatal Diagnosis 34: 1-7 (2014)), is hereby, withdrawn.
7. In light of Applicant’s amendment and arguments, the rejection of claim 289 under 35 U.S.C. 103 as being unpatentable over Hatt et al. (Prenatal Diagnosis 34: 1-7 (2014)) or Eckelt et al. (US 2013/0331284) in light of Hatt et al. (Prenatal Diagnosis 34: 1-7 (2014)) in view of MA et al. (China Academic Journal Electronic Publishing House. English Abstract (2017)- IDS) and Schwabe et al. (WO 2017/062672 A2- IDS), is hereby, withdrawn.
8. In light of Applicant’s amendment and arguments, the rejection of claims 284-286 under 35 U.S.C. 103 as being unpatentable over Eckelt et al. (US 2013/0331284) in light of Hatt et al. (Prenatal Diagnosis 34: 1-7 (2014)) in view of Liberti et al. (WO 02/06790 A1- IDS), is hereby, withdrawn.
9. In light of Applicant’s amendment and arguments, the rejection of claim 288 under 35 U.S.C. 103 as being unpatentable over Eckelt et al. (US 2013/0331284) in light of Hatt et al. (Prenatal Diagnosis 34: 1-7 (2014)) in view of Chuang et al. (Journal of Biological Chemistry 287 (18): 14389-14401 (April 27,2012)), is hereby, withdrawn.
Priority
10. Applicant’s claim for the benefit of a provisional application under 35 U.S.C. 119 (a)-(d) or (f), 365(a) or (b) or 386(a)111 and 37 C.F.R 1.53(b) is acknowledged. Based on the filing receipt, the effective filing date of this National Stage application, which is a 371 of PCT/IB2020/056632 filed 7/14/2020, is July 15, 2019 which is the filing date of Provisional Application 62/874,306 from which the benefit of priority is claimed.
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.
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.
11. Claims 278-283, 288, 290, and 292-299 are rejected under 35 U.S.C. 103 as being unpatentable over Eckelt et al. (US 2013/0331284) in view of WU et al. (US 2016/0053317).
Eckelt et al. disclose a method for isolating fetal cells from a maternal whole blood sample of a pregnant subject [0034, 0045]. The method comprises: (a) contacting the sample comprising a plurality of cells with a plurality of magnetic particles (beads) conjugated to a first antibody (i.e. antibodies, ligand) to capture and bind to a fetal cell marker [0074, 0124, 0163, 0194, 0195]; (b) isolating cells that bound to the first antibody by subjecting the sample in a) to magnetic field (MACS) to produce an enriched sample [0194, 0195]; (c) contacting the enriched sample with a second antibody (i.e. antibodies) that binds to cytokeratin (CK18, keratin, KRT, CK) antigen, wherein the second antibody is conjugated to a fluorescent label (reporter dye: fluorescein) [0077, 0121-0124, 0155, 0171, 0194, 0195, 0253]; and, (d) detecting and isolating single fetal cells that further bound to the second antibody by positive selection using FACS or MACS [0192-0195, 0197, 0223].
Eckelt et al. teach that the first antibody conjugated to the plurality of magnetic particles that capture and bind to a fetal cell may be an epithelial marker [0074, 0124, 0163, 0194, 0195]. The fetal cell is a fetal nucleated red blood cell (fnRBC: fetal nucleated erythrocyte) [0006, 0207] or a fetal trophoblast [0293]. The magnetic particles are colloidal ferrofluid magnetic particles [0194, 0195]. Eckelt et al. also teach further contacting the enriched sample with an antibody to CD45 for negative selection of leukocytes [0192-0202]. Eckelt et al. further teach contacting the enriched sample with a nuclear stain including DAPI, spectrum green, and spectrum orange [0286, 0287]. The fluorescent-labeled fetal cells are isolated based on immunofluorescent technology, fluorescence activated cell sorting (FACS), or DEPArray (microarray analysis) [0192, 0222, 0223]. Eckelt et al. teach sequencing the isolated fetal cells and performing genomic or genetic analysis on the fetal cells [0059, 0073, 0124, 0219-0222].
With respect to claims 281 and 282, magnetic particles are inherently formed from ferromagnetic material and when in particulate form, are inherently in colloidal suspension; hence, colloidal ferrofluid magnetic particles, as recited in claims 281 and 282 [0194, 0195].
Eckelt et al. differ from the instant invention in failing to teach that the first antibody binds to CD71 or epithelial cell adhesion molecule (EpCAM).
WU et al. disclose a method for capturing and isolating fetal cells and/or fetal trophoblast containing fetal material (nucleated fetal cells) from a maternal blood sample of a pregnant subject to produce a fetal-enriched sample (Abstract; [0029]). The method comprises: (a) contacting the sample comprising a plurality of cells with a plurality of magnetic particles (magnetic particles in stationary phase) conjugated to a capture (first) antibody which is either one of anti-CD71 that binds to CD71 nucleated fetal cell biomarker on nucleated fetal cells containing the fetal DNA material or anti-EpCAM that binds to EpCAM on nucleated fetal cells [0006, 0009, 0013, 0018, 0025-0029, 0032, 0035, 0069, 0083]; and (b) isolating cells that bound to the first antibody by subjecting the sample a) to magnetic field (MACS) to produce an enriched nucleated fetal cell sample [0055, 0092, 0093]. Wu et al. also teach (c) contacting the nucleated fetal cell sample with a second antibody that binds to another nucleated fetal cell marker (i.e. MMP14, HbF, CD36), wherein the second antibody is conjugated to a fluorescent label (fluorescent molecules: FITC, Alexa Fluor) [0013, 0055, 0059, 0065] and (d) detecting and isolating single fetal cells that further bound to the second antibody using FACS or MACS [0059]. WU et al. also teach further contacting the enriched sample with an antibody to CD45 for negative selection of leukocytes [0013]
It would have been obvious to one of ordinary skill in the art before the effective filing date of the instant invention to substitute the first antibody of Eckelt with ant-CD71 or anti-EpCAM as taught by WU because WU taught that CD71 and EpCAM are fetal biomarkers in nucleated fetal cells that carry fetal material necessary for further DNA analysis and specifically used ant-CD71 or anti-EpCAM to capture and isolate these nucleated fetal cells for applications in methods of producing enriched nucleated fetal cell samples from maternal blood such as the method taught by Eckelt. One of ordinary skill would have had reasonable expectation of success in incorporating the ant-CD71 or anti-EpCAM antibodies as taught by WU into the fetal cell enrichment and isolation method of Eckelt for conjugation with magnetic particles to capture and isolate nucleated fetal cells because both of Eckelt and WU teach analogous art in specifically isolating and enriching nucleated fetal cells from maternal blood for further analysis of fetal DNA material.
12. Claims 284-286, 0316, and 0317 are rejected under 35 U.S.C. 103 as being unpatentable over Eckelt et al. (US 2013/0331284) in view of WU et al. (US 2016/0053317) as applied to claim 278 and 283 above, and in further view of Liberti et al. (WO 02/06790 A1- IDS).
Eckelt et al. and WU et al. are discussed supra. Eckelt et al. and WU et al. differ from the instant invention in failing to teach magnetic particles coupled to a first and a second exogenous aggregation enhancing factor (EAEF).
Liberti et al. disclose compositions and methods which enhance analysis of biological entities such as cells by controlling and inhibiting aggregation of magnetic particles, and eliminating interfering magnetic clusters created by naturally occurring aggregators of colloidal magnetic particles (Abstract). Liberti et al. specifically teach a reagent composition comprising magnetic particles coupled to a first exogenous aggregation enhancing factor (EAEF) which comprises a first member of a specific binding pair which may be any one of antigen-antibody, biotin-streptavidin, receptor-hormone, receptor-ligand, agonist-antagonist, lectin-carbohydrate, Protein A- antibody Fc, avidin-biotin, biotin analog-avidin, desthiobiotin-streptavidin, desthiobiotin-avidin, iminobiotin-streptavidin, and iminobiotin-avidin (p. 15, line 19 to p. 16, line 10; p. 17, lines 18-32; p. 18, lines 26-32). Liberti et al. further teach adding to the blood test sample a second EAEF to induce aggregation of the magnetic particles which comprises the other member of the specific binding pair (p. 17, lines 32 to p. 18, line 9; p. 18, lines 26-32). Liberti et al. also teach adding to the enriched cell sample a member of the specific binding pair to reverse aggregation of the magnetic particles (p. 20 lines 26-35). Moreover, Liberti et al. teach adding to the blood sample, one or more inhibitors effective to inactivate and inhibit endogenous ferrofluid aggregation factors comprising reducing agents and bovine serum albumin (animal serum proteins) (p. 20 line 26 to p. 21, line 8).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the instant invention to have incorporated the teaching of Liberti on using EAEF in magnetic particle-based isolation methods into the nucleated fetal cell enrichment or isolation method of Eckelt as modified by WU obtained from maternal pregnant subjects because Liberti taught that EAEF is efficient in controlling magnetic particle aggregation and inhibiting or removing endogenous aggregation factors involved in cell selection and isolation methods. One of ordinary skill would have had reasonable expectation of success in incorporating the teaching of Liberti into the magnetic particle-based fetal cell enrichment and isolation method of Eckelt as modified by WU because all of Eckelt, WU, and Liberti teach analogous art in magnetic particle-based specific cell selection, enrichment, and isolation methods.
Response to Arguments
13. Applicant’s arguments with respect to claims 278-286, 288, 290 and 292-299 have been considered but are moot in light of the new grounds of rejection necessitated by Applicant’s amendment and because the new grounds of rejection do not rely on any reference applied in the prior rejection of record for any teaching or matter specifically challenged in the argument.
Allowable Subject Matter
14. Claim 289 is objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
15. No claims are allowed.
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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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Gregory S. Emch can be reached at (571) 272-8149. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/GAILENE GABEL/Primary Examiner, Art Unit 1678
May 29, 2026
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