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
This application 18/054,841 filed on 11/11/2022 claims the benefit of provisional U.S. Patent Application No. 63/278,341, filed on 11/11/2021.
The priority date of claim 2 and its dependent claims 1, 3-18, 20, 22, 23, 25-27, 30 and 31 is determined to be 11/11/2021, the filing date of provisional U.S. Patent Application No. 63/278,341.
Status of Claims
Applicant’s amendments to claims filed 02/18/2026 in response to the Non-Final Rejection mailed 11/18/2025 are acknowledged.
Claims 2, 16, and 20 are amended.
Claims 8, 15, 18, 25-26, and 30-31 have been canceled.
Claims 1-7, 9-14, 16,17, 20, 22, 23, and 27 are pending and under examination.
Response to Remarks filed 02/18/2026
The amendments and arguments presented in the papers filed 02/18/2026 ("Remarks”) have been thoroughly considered. The issues raised in the Office action dated 11/18/2025 listed below have been reconsidered as indicated.
a) The 35 USC 112(b) indefiniteness rejections of claims 2, 8, 25, 30, and 31 are moot in view of amendments to claim 2 and the cancellation of the claims 8, 25, 30, and 31.
b The rejection of claim 15 under 35 U.S.C. 112(d) for being of improper dependent form is moot in view of the cancellation of the claims.
c) The rejection of claims 25, 26, 30, and 31 under 35 U.S.C. 101 is moot in view of the cancellation of the claims.
d) The rejection of claims 1-4, 7-13, 15-18, 25, 26, 30, and 31 under 35 U.S.C. 103 as being unpatentable over Tereba et al. (US PGPub 20060057715) and Walsh et al. (Chelex 100 as a Medium for Simple Extraction of DNA for PCR-Based Typing from Forensic Material. 2013. BioTechniques, 54(3), 134–139) are withdrawn in view of the amendments to the claims and cancellation of claims 8, 15, 18, 25, 26, 30, and 31.
e) The rejection of claims 5 and 6 under 35 U.S.C. 103 as being unpatentable over Tereba et al. (US PGPub 20060057715) and Walsh et al. (Chelex 100 as a Medium for Simple Extraction of DNA for PCR-Based Typing from Forensic Material. 2013. BioTechniques, 54(3), 134–139) and further in view of Invitrogen (Herring Sperm DNA Solution. Pub 6/11/01. p. 1-4) are withdrawn in view of the amendments to the claims.
f) The rejection of claims 14 and 27 under 35 U.S.C. 103 as being unpatentable over Tereba et al. (US PGPub 20060057715) and Walsh et al. (Chelex 100 as a Medium for Simple Extraction of DNA for PCR-Based Typing from Forensic Material. 2013. BioTechniques, 54(3), 134–139) and further in view of Liu (US PGPub 20090042255) are withdrawn in view of the amendments to the claims.
g) The rejection of claims 20, 22, and 23 under 35 U.S.C. 103 as being unpatentable over Tereba et al. (US PGPub 20060057715) and Walsh et al. (Chelex 100 as a Medium for Simple Extraction of DNA for PCR-Based Typing from Forensic Material. 2013. BioTechniques, 54(3), 134–139) as applied to claims 1- 4,7-13, 15-18, 25, 26, 30, and 31 above, and further in view of Yoshida et al. (The modified method of two-step differential extraction of sperm and vaginal epithelial cell DNA from vaginal fluid mixed with semen. Forensic Sci Int. 1995 Mar 21;72(1):25-33) are withdrawn in view of the amendments to the claims.
New and modified grounds of rejection necessitated by amendment are detailed below and this action is made FINAL.
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.
Claims 1-4, 7, 9-14, 16,17, 20, 22, 23, and 27 are rejected under 35 U.S.C. 103 as being unpatentable over Liu (US PGPub 20080281089) in view of Tereba et al. (US PGPub 20060057715).
The following are new rejections necessitated by claim amendments
Regarding claim 2 parts (a) and (b), Liu teaches a method for differential extraction of sperm cells, the method comprising placing a biological sample that comprises sperm cells and non-sperm cells (epithelial cells, para 29) in a first compartment comprising a cell-trapping matrix and capturing the sperm cells with the cell-trapping matrix (claim 10). Exemplary cell-trapping matrices include Dynabeads® WCX, a cation exchange resin (para 51).
Regarding part (c), Liu teaches transferring a wash buffer to the compartment with the cell-trapping matrix (para 92), which reads on washing the cationic exchange resin with a wash buffer.
Regarding part (d), Liu teaches a selective sperm lysis buffer that lyses captured sperm cells and adding an elution buffer that releases DNA from DNA-binding particles and/or cell-trapping matrix (paras 10, 34) but does not teach a single elution buffer that lyses the captured sperm and also elutes the DNA.
Further regarding part (a), Liu teaches a general lysis buffer that lyses non-sperm cells (epithelial cells) and may or may not also lyse sperm cells (para 36),and that after lysis of one cell type, at least 50% of the intact cells are captured by the cell-trapping matrix (para 62) but does not teach using the general lysis buffer before binding the sperm cells with the cell-trapping matrix. Liu states that it is often desirable to separate the sperm cells and epithelial cells prior to analysis and that separation and isolation in order to create an accurate profile is important for identification of an assailant (para 4) but does not teach a method for doing so.
Tereba teaches a method for isolating sperm cells from a sample, the method comprising: treating material with a protease, such as Proteinase K, under conditions that allow lysis of the epithelial cells, but do not promote lysis of the sperm cells (para 16).
It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Liu and Tereba to arrive at the instantly claimed invention. The modification would have entailed isolating the sperm cells as taught by Tereba before capture by the cell-trapping matrix as taught by Liu. One would have been motivated by the benefit of Tereba in separating the sperm cells and epithelial cells in order to create a more accurate profile for identifying an assailant. The modification would further have entailed combining the selective sperm lysis buffer and the elution buffer of Liu in order to lyse the captured sperm and elute the DNA in one buffer. Liu teaches many different combinations of buffers in different compartments and in different orders (see for example paras 10-11 and Figs 1-6). Selecting a particular order and combination of buffers would have been considered well-known, routing and conventional . One of skill in the art would have been motivated to optimize conditions for retrieval of sperm DNA. There would have been a reasonable expectation of success given the underlying materials and methods are widely known, successfully demonstrated, and commonly used as evidenced by the prior art.
Regarding claim 1, Liu does not teach a step separating a sperm-cell-enriched fraction of the sample from a sperm-cell-depleted fraction of the sample between steps (a) and (b).
Tereba teaches pelleting the sperm cells and removing the epithelial cell DNA in the aqueous layer (para 23), and adding resin to solution containing the sperm cells (para 33).
It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Liu and Tereba to arrive at the instantly claimed invention. The modification would have entailed using the digestion and isolation steps of Tereba prior to contacting the sample with the cell-capturing matrix of Liu. One would have been motivated by the benefit of a sample enriched for sperm cells before capture. Liu teaches the method must be modified when a sample comprises an excess of non-sperm cells relative to sperm cells, resulting in residual DNA (para 84). One of skill in the art would have recognized the advantage of decreasing the excess of non-sperm cells to increase the successful isolation of sperm cells. There would have been a reasonable expectation of success given the underlying materials and methods are widely known, successfully demonstrated, and commonly used as evidenced by the prior art.
Regarding claim 3, both Liu and Tereba teach a digestion agent containing Proteinase K (Tereba para 30).
Regarding claim 4, both Liu and Tereba teach digestion agent containing SDS (Liu para 36; Tereba para 30).
Regarding claim 7, neither Liu nor Tereba teach the digestion agent is incubated with the sample at a temperature of at least about 37°C.
However, it would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to modify the reaction conditions using the digestion agent of Tereba or Liu to arrive at the instantly claimed invention. Determining an appropriate temperature range is deemed merely a matter of judicious selection and routine optimization which is well within the purview of the skilled artisan. One of ordinary skill in the art would have been motivated to try different temperatures in order optimize conditions of the digestion reaction and optimize the efficiency of lysing epithelial cells. There would have been a reasonable expectation of success given the underlying materials and methods of DNA sequencing by synthesis and nucleotide analogs are widely known, successfully demonstrated, and commonly used as evidenced by the prior art.
Regarding claim 9, Liu does not explicitly teach discarding the sperm-cell-depleted fraction.
Tereba teaches removing the epithelial cell DNA in the aqueous layer (para 23), which reads on discarding the sperm-cell-depleted fraction.
It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Liu and Tereba to arrive at the instantly claimed invention. The modification would have entailed discarding the separated aqueous captures epithelial cells as taught by Tereba. In the alternate, Liu teaches embodiments that separate the non-sperm cell and sperm-cell enriched fractions (para 12), and one of skill in the art would have known that the non-sperm cell (i.e. sperm-cell depleted fraction), could be discarded once sperm cells were lysed and DNA was captured for analysis.
One would have been motivated by a desire to clean the sperm enriched fraction for analysis. There would have been a reasonable expectation of success given the underlying materials and methods are widely known, successfully demonstrated, and commonly used as evidenced by the prior art.
Regarding claims 10 and 11, Liu teaches the non-sperm cells remain captured (are retained) on the cell-trapping matrix after incubating the cell-trapping matrix in the selective sperm lysis buffer, resulting in a sperm-cell depleted fraction comprising non-sperm cells. In certain embodiments, the non-sperm cells are lysed and the non-sperm cell DNA is bound (obtained) (para 12). Liu further teaches the non-sperm cell DNA can be subjected to DNA analysis (para 95).
Regarding claim 12, Liu teaches DNA analysis including Restriction Fragment Length Polymorphism (RFLP) analysis, which reads on quantifying the sperm-depleted DNA.
Regarding claim 13, Liu teaches using DNA analysis for human identification, which reads on genotyping (para 72).
Regarding claim 14, Liu teaches Short Tandem Repeat (STR) analysis of isolated DNA (para 70).
Regarding claim 16, Tereba teaches sperm cells are pelleted by centrifugation (para 14), satisfying the requirement of separating the sperm-cell-enriched fraction from the sperm-cell-depleted fraction by centrifugation.
Regarding claim 17, Liu teaches cell trapping matrices comprise paramagnetic, particles (para 50).
Regarding claims 20 and 22, Liu does not teach the elution buffer comprises a detergent, a digestion agent, and a reducing agent.
However, Liu teaches a general lysis buffer comprising SDS (detergent) and proteinase K (digestion agent) (para 36) and selective sperm lysis buffer comprising a disulfide bond reducing agent such as DTT or TCEP (para 40).
Thus, it would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to modify the teachings of Liu to arrive at the instantly claimed invention. The modification would have entailed combining the disulfide bond reducing agent of the selective sperm lysis buffer with the general lysis buffer. One would have been motivated to make the modification in order to break the disulfide bonds of sperm cells for sperm specific lysis with the lysis reagents of the general lysis buffer as taught by Liu. Liu states that one skilled in the art can select a lysis buffer based on the intended use, in this case successfully lysing captured sperm. There would have been a reasonable expectation of success given the underlying materials and methods are widely known, successfully demonstrated, and commonly used as evidenced by the prior art.
Regarding claim 23, Liu does not teach the sperm-associated DNA is eluted from the cation-exchange resin by heating the cationic exchange resin in the elution buffer to at least 65 °C.
However, it would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to modify the elution reaction conditions using the modified lysis buffer of Liu to arrive at the instantly claimed invention. Determining an appropriate temperature range is deemed merely a matter of judicious selection and routine optimization which is well within the purview of the skilled artisan. One of ordinary skill in the art would have been motivated to try different temperatures in order optimize conditions of the digestion reaction and optimize the efficiency of lysing epithelial cells. There would have been a reasonable expectation of success given the underlying materials and methods of DNA sequencing by synthesis and nucleotide analogs are widely known, successfully demonstrated, and commonly used as evidenced by the prior art.
Regarding claim 27, Liu teaches a fluid-handling and/or magnetic particle-handling instrument (para 24), including instruments such as the BioRobot EZ1 Workstation, which satisfies the requirement of one or more automated steps.
Claims 5 and 6 are rejected under 35 U.S.C. 103 as being unpatentable over Liu (US PGPub 20080281089) in view of Tereba et al. (US PGPub 20060057715) as applied to claims 1-4, 7, 9-14, 16,17, 20, 22, 23, and 27 above, and further in view of Invitrogen (Herring Sperm DNA Solution. Pub 6/11/01. p. 1-4).
The following are new rejections necessitated by claim amendments
Regarding claims 5 and 6, neither Liu nor Tereba teach step (a) further comprises contacting the sample with a blocking agent (claim 5); or wherein the blocking agent comprises Herring Sperm DNA or poly-deoxy-inosinic-deoxy-cytidylic acid (poly d(I-C)) (claim 6).
Invitrogen teaches using Herring Sperm DNA as a blocking agent before hybridization of nucleic acids to reduce non-specific binding to the surface of the filter (p. 1), satisfying the requirements of both claims 5 and 6.
It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of L:iu and Tereba with Invitrogen to arrive at the instantly claimed invention. The modification would have entailed a step of adding Herring Sperm DNA before the sperm-associated DNA of the sample. One would have been motivated to add the blocking step in order to decrease non-specific binding to the resin. There would have been a reasonable expectation of success given the underlying materials and methods are widely known, successfully demonstrated, and commonly used as evidenced by the prior art.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
(I). (i). Independent claim 2 and its dependent claims 1, 3, 4, 7, 9-13, 17, 20, 22, 23 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-14 of U.S. Patent No. 12,338,432 in view of Liu (US PGPub 20080281089) in view of Tereba et al. (US PGPub 20060057715).
Although the claims at issue are not identical, they are not patentably distinct from each other because both are directed to extracting DNA from sperm and non-sperm cells using resin.
Regarding instant claim 2, claim 1 of the ‘432 patent requires (a) contacting a sample comprising sperm cells with a digestion agent; contacting the sample with resin; washing the resin with a wash buffer; and eluting sperm-associated DNA.
The claims of the ‘432 patent do not require the resin is a cation exchange resin.
The teachings of Liu as they relate to this claim are given previously in this office action and are fully incorporated here.
Regarding instant claim 1, claim 4 of the ‘432 patent requires separating a sperm-cell-enriched fraction of the sample from a sperm-cell-depleted fraction of the sample.
Regarding instant claim 3, claim 1 of the ‘432 patent requires a digestion agent comprising proteinase K.
Regarding instant claim 4, claim 2 of the ‘432 patent requires the detergent comprises sodium dodecyl sulfate (SDS).
Regarding instant claim 7, the claims of the ‘432 patent do not require the digestion agent is incubated with the sample at a temperature of at least about 37°C (instant claim 7).
The teachings of Liu and Tereba as they relate to this claim is given previously in this office action and are fully incorporated here.
Regarding instant claim 9, claim 5 of the ‘432 patent requires the sperm-cell-enriched fraction is used in steps (d) through (f), i.e. the sperm-cell depleted fraction is discarded.
Regarding instant claim 10, claim 6 of the ‘432 patent requires the sperm-cell-depleted fraction is retained for subsequent analysis.
Regarding instant claim 11, claim 6 of the ‘432 patent requires obtaining sperm-depleted DNA from the sperm-cell-depleted fraction.
Regarding instant claim 12, claim 6 of the ‘432 patent requires quantifying the sperm-depleted DNA.
Regarding instant claim 13, claim 6 of the ‘432 patent requires genotyping the sperm-depleted DNA.
Regarding instant claim 14, the claims of the ‘432 patent do not require genotyping the sperm-depleted DNA comprises performing short tandem repeat (STR) analysis.
The teachings of Liu as they relate to this claim are given previously in this office action and are fully incorporated here.
Regarding instant claim 16, the claims of the ‘432 patent do not require the sperm-cell-enriched fraction is separated from the sperm-cell-depleted fraction by centrifugation (instant claim 16).
The teachings of Tereba as they relate to this claim are given previously in this office action and are fully incorporated here.
Regarding instant claim 17, claim 8 of the ‘432 patent requires the cellulose resin comprises a paramagnetic cellulose resin.
Regarding instant claim 20, claims 1 and 9 of the ‘432 patent require an elution buffer capable of lysing the cellulose-resin-bound sperm cells (i.e. detergent) and comprising a digestion agent and a reducing agent.
Regarding instant claim 22, claim 10 of the ‘432 patent requires the digestion agent comprises proteinase K and the reducing agent comprises DTT, TCEP, BME, GSH, and/or 1-TG.
Regarding instant claim 23, claim 11 of the ‘432 patent requires the sperm-associated DNA is eluted from the cellulose resin by heating the cellulose resin in the elution buffer.
Regarding instant claim 27, the claims of the ‘432 patent do not require one or more of the steps are automated.
The teachings of Liu as they relate to this claim are given previously in this office action and are fully incorporated here.
(ii). Claims 5 and 6 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-14 of U.S. Patent No. 12,338,432 in view of Invitrogen (Herring Sperm DNA Solution. Pub 6/11/01. p. 1-4)..
Regarding instant claims 5 and 6, the claims of the ‘432 patent do not require step (a) further comprises contacting the sample with a blocking agent (instant claim 5); or the blocking agent comprises Herring Sperm DNA or poly-deoxy-inosinic-deoxy-cytidylic acid (poly d(I-C)) (instant claim 6)
The teachings of Invitrogen as they relate to these claims are given previously in this office action and are fully incorporated here.
Conclusion
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.
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/JESSICA GRAY/Examiner, Art Unit 1682
/WU CHENG W SHEN/Supervisory Patent Examiner, Art Unit 1682
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