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 18/047,242 filed on 10/17/2022 is a Continuation-in-Part of U.S. Patent Application No 17/643,161, filed 12/07/2021 and claims the benefit of Taiwan Application No. 109145792, filed on 12/23/2020.
It is noted that an English translation of the Taiwanese Application was submitted on 8/20/2025 in the parent case 17/643,161.
The priority date of claims 1 and its dependent claims 2-7 and 11-13 is determined to be 12/23/2020, the filing date of Taiwanese Application No. 109145792.
Status of Claims
Applicant’s amendments to claims filed 02/03/2026 in response to the Non-Final Rejection mailed 11/04/2025 are acknowledged.
Claims 1, 2, and 7 are amended.
New claims 11-13 are acknowledged
Claims 1-7 and 11-13 are pending and under examination.
Response to Remarks filed 02/03/2026
The amendments and arguments presented in the papers filed 02/03/2026 ("Remarks”) have been thoroughly considered. The issues raised in the Office action dated 11/04/2025 listed below have been reconsidered as indicated.
a) The objection to claim 2 is withdrawn in view of the amendments to the specification.
b) The rejection of claims 1-7 under 35 U.S.C. 103 as being unpatentable over Benet et al. (US 20130224737, on IDS dated 08/25/2025) in view of Chrambach et al. (Polyacrylamide Gel Electrophoresis.1971. Science, 172: 440-451, on IDS dated 08/25/2025) and Sestili, et al. (The Fast-Halo Assay for the Assessment of DNA Damage at the Single-Cell Level. 2009 In: Vengrova, S., Dalgaard, J. (eds) DNA Replication. Methods in Molecular Biology, vol 521. Humana Press. p 517-533) are withdrawn in view of the amendments to the claims.
c) The double patenting rejection of claims 1-7 as being unpatentable over (i) U.S. Patent No. 11,644,455, (ii) U.S. Patent No. 12,153,039, and (iii) copending Application No. 17/643,161 in view of Benet et al. (US 20130224737, on IDS dated 08/25/2025) in view of Chrambach et al. (Polyacrylamide Gel Electrophoresis.1971. Science, 172: 440-451, on IDS dated 08/25/2025) and Sestili, et al. (The Fast-Halo Assay for the Assessment of DNA Damage at the Single-Cell Level. 2009 In: Vengrova, S., Dalgaard, J. (eds) DNA Replication. Methods in Molecular Biology, vol 521. Humana Press. p 517-533) are withdrawn in view of the amendments to the claims.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 Objections - New
Claim 1 is objected to because of the following informalities:
The claim recites “indicative of the presence of SDF” and “indicative of the absence of SDF” without defining SDF as sperm DNA fragmentation.
The phrase "determining DFI in the seman sample" appears to be a typographical error intended to be "determining DFI in the semen sample". Appropriate correction is required.
Claim Interpretation
The preamble of claim 1recites “A method for determining DNA fragmentation index (DFI) in a semen sample from a human subject”. However, the method steps in the claim only require a) embedding the semen sample containing sperm cells in a polyacrylamide gel --; (b) without DNA denaturation, treating the sperm cells-embedded gel with a lysis solution --; (c) subjecting the treated gel in step (b) to DNA staining ---; and (d) detecting the presence or the absence of a halo formation around a head of each sperm cell--- and determining DFI---” . For purposes of examination, carrying out the active steps of embedding, treating with a lysis solution, preforming DNA staining, and detecting the presence or absence of a halo are considered to fulfill the requirements for “determining DFI”.
Claim Rejections - 35 USC § 101 - New
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 1-7 and 11-13 are rejected under 35 U.S.C. 101 because the claimed invention is directed to non-statutory subject matter.
35 U.S.C. § 101 requires that to be patent-eligible, an invention (1) must be directed to one of the four statutory categories, and (2) must not be wholly directed to subject matter encompassing a judicially recognized exception. M.P.E.P. § 2106. Regarding judicial exceptions, “[p]henomena of nature, though just discovered, mental processes, and abstract intellectual concepts are not patentable, as they are the basic tools of scientific and technological work.” Gottschalk v. Benson, 409 U.S. 63, 67 (1972); see also M.P.E.P. § 2106, part II.
Based upon consideration of the claims as a whole, as well as consideration of elements/steps recited in addition to the judicial exception, the present claims fail to meet the elements required for patent eligibility.
Step 1
The claimed invention is directed to the statutory category of a process.
Step 2A, Prong One
The claim is (claims are) taken to be directed to an abstract idea, a judicial exception.
Claim 1 is directed to a method comprising “detecting the presence or the absence of a halo formation --- and determining DFI in the seman [sic] sample”. This limitation is an abstract mental process (see MPEP 2106.04(a)(2)(III)). As written, the determining step encompasses the mental step of making visual observations and making mental judgements.
Claims 2-7 and 11-13 depend from claim 1, and require the same step of “determining DFI”.
Step 2A, Prong Two
The exception is not integrated into a practical application of the exception. The claims do not recite any additional elements that integrate the exception into a practical application of the exception.
While claim 1 recites ”(a) embedding the semen sample containing sperm cells in a polyacrylamide gel --; (b) without DNA denaturation, treating the sperm cells-embedded gel with a lysis solution --; (c) subjecting the treated gel in step (b) to DNA staining ---”, these steps are not an integration of the exception into a practical application. Instead, these elements are data gathering required to perform the method.
Furthermore, while claim 1 recite ”(d) detecting the presence or the absence of a halo formation around a head of each sperm cell, wherein the presence of halo formation is indicative of the presence of SDF, and the absence of halo formation is indicative of the absence of SDF”, these are not integrations of the exception into a practical application. Rather, these detecting steps are mere data analysis required to perform the method. (See MPEP 2106.04(a)(2)(III); claims to "collecting information, analyzing it, and displaying certain results of the collection and analysis," where the data analysis steps are recited at a high level of generality such that they could practically be performed in the human mind, Electric Power Group v. Alstom, S.A., 830 F.3d 1350, 1353-54, 119 USPQ2d 1739, 1741-42 (Fed. Cir. 2016).
Step 2B
The claim does not include additional elements that are sufficient to amount to significantly more than the judicial exception. The claim does not add a specific limitation other than what is well-understood, routine, and conventional in the field. Steps directed to embedding, lysing and DNA staining are techniques that are routine, conventional, and well-known in the art as demonstrated in the 102/103 rejection documented below.
For these reasons, the claims are rejected under section 101 as being directed to non-statutory subject matter.
Claim Rejections - 35 USC § 112(b) - New
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 1-7 and 11-13 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 1 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being incomplete for omitting essential steps, such omission amounting to a gap between the steps. See MPEP § 2172.01. Claim 1 recites the limitation “determining DFI in the semen sample”. The omitted steps appear to be: steps for determining DFI . Claim 1 should clearly delineate all active steps required for performing the claimed methods.
Claims 2-7 and 11-13 are similarly indefinite because they directly or indirectly depend from claim 1.
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 1-7 and 11-13 are rejected under 35 U.S.C. 103 as being unpatentable over Benet et al. (US 20130224737, on IDS dated 08/25/2025) in view of Carvalho et al. (Cryogel poly (acrylamide): synthesis, structure and applications.2014. Separation & Purification Reviews. 43(3): 241-262) and Sestili, et al. (The Fast-Halo Assay for the Assessment of DNA Damage at the Single-Cell Level. 2009 In: Vengrova, S., Dalgaard, J. (eds) DNA Replication. Methods in Molecular Biology, vol 521. Humana Press. p 517-533).
The following are new rejections necessitated by amendments
Regarding claim 1, Benet teaches a method for determining cells that contain ROS (reactive oxygen species) (i.e. DNA damage) in a semen sample (para 97), the method comprising: contacting a cellular population from a semen sample with a thickening agent (i.e. a gel) (Benet claim 1 step a) where thickening agents include polyacrylamide (para 50). Benet teaches the method further comprises treating the sample with a lysis solution, staining the sperm with a DNA probe, and detecting halos (para 82), wherein the presence of halos is indicative of sperm DNA fragmentation (para 76). Benet teaches a lysis solution can contain at least one detergent such as SDS and at least one chaotropic agent such as urea (para 79).
Benet does not teach the lysis solution comprises 0.5-4 M urea and 0.05-0.5% (w/v) SDS.
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 Benet to arrive at the instantly claimed invention. Determining an appropriate percentage (of SDS) or molarity (of urea) to achieve a desired effective removal of membranes and proteins in a particular gel environment is deemed merely a matter of judicious selection and routine optimization which is well within the purview of the skilled artisan. 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.
Benet further does not teach: regarding step (a) a polyacrylamide gel in which the gel-forming materials consist of acrylamide and bis-acrylamide, to obtain a sperm cells-embedded gel, wherein the gel has a pore size from 3 to 9 nm, regarding step (b) lysing nuclear proteins without DNA denaturation, or regarding step (c) the absence of halo formation is indicative of the absence of SDF – and determining DFI in the semen sample.
Regarding step (a), Carvalho teaches synthesis of cryogels (polyacrylamide gels) used for purification of DNA (abstract). Carvalho teaches polyacrylamide gels which consist of acrylamide and bis-acrylamide (Table 1), wherein the gel has a pore size from 3 to 9 nm (Fig. 2). Carvalho teaches that the pore size of the network can be determined by adjusting parameters (p. 5).
Regarding steps (b) and (c), Sestili teaches a method for detecting DNA damage in individual cells (the fast halo assay, FHA), the method comprising embedding cells in a gel and adding a lysis solution in non-denaturing conditions, staining DNA (p. 522), and imaging the labeled DNA (p. 523). Sestili teaches moderately and highly damaged cells are characterized by halos and non-damaged cells do not have halos (Fig. 2).
Sestili states that the assay is sensitive, reliable, and flexible, as well as the most rapid and less expensive option compared to other existing methods (p. 517, Abstract). Sestili further states that their denaturing FHA assay is well suited for the detection of DNA double-stranded breaks and damage by particular agents (p. 527).
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 Benet with Carvalho and Sestili to arrive at the instantly claimed invention. The modification would have entailed using the gel of Carvalho as the embedding material of Benet. Differences in pore size are routine optimizations known in the art and Carvalho provides guidance for producing a range of pore sizes. The courts have found "[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 MPEP 2144.05.01. One of ordinary skill in the art would have been motivated to optimize for a pore size that provided optimal resolution between fragmented and non-fragmented DNA. The modification would further have entailed using the non-denaturing conditions of Sestili in the method of Benet. One would have been motivated by the sensitivity and reliability provided by the conditions of Sestili to differentiate between cells with no DNA damage and cells with moderate or high DNA damage. One of skill in the art would further have been motivated to combine the control of resolution of the gel of Carvalho with the sensitivity and reliability of the conditions of Sestili. 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 2, Benet teaches a lysis solution with at least one reducing agent such as dithiothreitol or tris(2-carboxyethyl)phosphine (para 81).
Regarding claims 3 and 4, neither Benet, Carvalho nor Sestili teach the lysis solution comprises 0.5-1 M urea, 0.05-0.5 % SDS, and 0.05-0.2 M TCEP (claim 3) or the lysis solution comprises 0.5-1 M urea, 0.05-0.1 % SDS, and 0.05-0.2 M TCEP (claim 4).
However, Benet teaches the lysis solution can contain at least one detergent such as SDS, at least one chaotropic agent such as urea and at least one reducing agent such as TCEP (para 79).
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 Benet to arrive at the instantly claimed invention. Determining an appropriate percentage (of SDS) or molarity (of urea and TCEP) to achieve a desired effective removal of membranes and proteins in a particular gel environment is deemed merely a matter of judicious selection and routine optimization which is well within the purview of the skilled artisan. 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 5, Carvalho teaches synthesis of gels that contain polyacrylamide (p. 5) and comprise acrylamide at a concentration from 7% (w/v) to 13% (w/v) (Fig. 2).
Regarding claim 6, neither Benet, Carvalho nor Sestili teach the lysis solution comprises 0.5-1 M urea, 0.05-0.1% SDS, and 0.05-0.2 M TCEP.
However, Benet teaches the lysis solution can contain at least one detergent such as SDS, at least one chaotropic agent such as urea and at least one reducing agent such as TCEP (para 79).
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 Benet to arrive at the instantly claimed invention. Determining an appropriate percentage (of SDS) or molarity (of urea and TCEP) to achieve a desired effective removal of membranes and proteins in a particular gel environment is deemed merely a matter of judicious selection and routine optimization which is well within the purview of the skilled artisan. 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 7, Benet teaches a DNA probe (i.e. stain) that is preferably DAPI (para 82).
Regarding claim 11, Carvalho teaches polyacrylamide gels containing acrylamide at a concentration ranging from 3% (w/v) to 22% (w/v) (Table 1 and Fig. 2).
Regarding claim 12, Carvalho teaches polyacrylamide gels containing acrylamide at a concentration ranging from 4% (w/v) to 16% (w/v) (Table 1 and Fig. 2).
Regarding claim 13, Carvalho teaches polyacrylamide gels wherein the gel has a pore size from 3.3 to 8.8 nm (4% to 22% w/v acrylamide) (Fig. 2).
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). Claims 1-7 and 11-13 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of U.S. Patent No. 11,644,455 in view of Benet et al. (US 20130224737, on IDS dated 08/25/2025) in view of Carvalho et al. (Cryogel poly (acrylamide): synthesis, structure and applications.2014. Separation & Purification Reviews. 43(3): 241-262) and Sestili, et al. (The Fast-Halo Assay for the Assessment of DNA Damage at the Single-Cell Level. 2009 In: Vengrova, S., Dalgaard, J. (eds) DNA Replication. Methods in Molecular Biology, vol 521. Humana Press. p 517-533).
Although the claims at issue are not identical, they are not patentably distinct from each other because the ‘455 patent discloses a method for detecting sperm DNA fragmentation in a semen sample. The additional limitations of the ‘455 claims are encompassed by the open claim language "comprising" found in the instant claims.
Claims 1, and 7 of the ‘455 patent require elements of a method that satisfy the requirements of instant claim 1.
Regarding instant claim 1, claim 1 of the ‘455 patent requires (a) embedding the semen sample containing semen cells in a gel comprising agarose, acrylamide, or alginate; (c) subjecting the gel obtained to a lysis treatment with a lysis solution; (d) subjecting the lysed gel obtained in step (c) to DNA staining; and (e) observing the presence or the absence of halo formation around heads of the sperm cells.
Regarding instant claim 1, claim 7 of the ‘455 patent requires (a) heating an agarose solution, adding a semen sample containing sperm cells to the heated agarose solution to form a mixture; (b) subjecting the mixture to a gel polymerization reaction, to obtain an agarose gel with the sperm cells containing denatured DNA embedded within; (c) subjecting the polymerized agarose gel to a lysis treatment with a lysis solution comprising 0.5 M to 4 M urea and 0.05% to 0.5% (w/v) sodium dodecyl sulfate to lyse the nuclear proteins of the sperm cells embedded in the agarose gel; (d) subjecting the lysed agarose gel obtained in step (c) to DNA staining; and (e) observing the presence or the absence of halo formation around heads of the sperm cells.
Claims of the ‘455 Patent do not require the gel has a pore size from 3 to 9 nm or lysing the sperm embedded cells without denaturant or the absence of halo formation is indicative of the absence of SDF. The teachings of Benet, Carvalho and Sestili as they relate to these claims are given previously in this office action and are fully incorporated here.
Regarding instant claims 2-7, claims of the ‘455 patent do not require the lysis solution further comprising a reducing agent of dithiothreitol (DTT), or tris(2-carboxyethyl) phosphine (TCEP) hydrochloride (instant claim 2); the lysis solution comprises 0.5-1 M urea, 0.05-0.5 % SDS, and 0.05-0.2 M TCEP (instant claims 3 and 6); the lysis solution comprises 0.5-1 M urea, 0.05-0.1 % SDS, and 0.05-0.2 M TCEP (instant claim 4); the gel contains polyacrylamide and is formed by a gel-forming solution comprising acrylamide at a concentration from 7% (w/v) to 13% (w/v) (instant claim 5); or DNA staining conducted with a staining reagent selected from a group (instant claim 7).
The teachings of Benet, Carvalho and Sestili as they relate to these claims are given previously in this office action and are fully incorporated here.
(II). Claims 1-7 and 11-13 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of U.S. Patent No. 12,153,039 in view of Benet et al. (US 20130224737, on IDS dated 08/25/2025) in view of Carvalho et al. (Cryogel poly (acrylamide): synthesis, structure and applications.2014. Separation & Purification Reviews. 43(3): 241-262) and Sestili, et al. (The Fast-Halo Assay for the Assessment of DNA Damage at the Single-Cell Level. 2009 In: Vengrova, S., Dalgaard, J. (eds) DNA Replication. Methods in Molecular Biology, vol 521. Humana Press. p 517-533).
Although the claims at issue are not identical, they are not patentably distinct from each other because the '039 patent discloses a method for detecting sperm DNA fragmentation in a semen sample. The additional limitations of the ‘039 claims are encompassed by the open claim language "comprising" found in the instant claims.
Regarding instant claim 1, claim 1 of the ‘039 patent requires (a) embedding the semen sample containing semen cells in a gel comprising agarose; (c) subjecting the gel obtained to a lysis treatment with a lysis solution at a concentration ranging from 0.5 M to 4 M and sodium dodecyl sulfate at a concentration ranging from 0.05% (w/v, g/mL) to 0.5% (w/v, g/mL); (d) subjecting the lysed gel obtained in step (c) to DNA staining; and (e)observing the presence or the absence of halo formation around heads of the sperm cells.
Regarding instant claim 1, claim 7 of the ‘039 patent requires (a) heating an agarose solution, adding a semen sample containing sperm cells to the heated agarose solution to form a mixture; (b) subjecting the mixture to a gel polymerization reaction, to obtain an agarose gel with the sperm cells containing denatured DNA embedded within; (c) subjecting the polymerized agarose gel to a lysis treatment with a lysis solution comprising 0.5 M to 4 M urea and 0.05% to 0.5% (w/v) sodium dodecyl sulfate to lyse the nuclear proteins of the sperm cells embedded in the agarose gel; (d) subjecting the lysed agarose gel obtained in step (c) to DNA staining; and (e) observing the presence or the absence of halo formation around heads of the sperm cells.
Claims of the ‘039 Patent do not require the gel has a pore size from 3 to 9 nm or lysing the sperm embedded cells without denaturant or the absence of halo formation is indicative of the absence of SDF. The teachings of Benet, Carvalho and Sestili as they relate to these claims are given previously in this office action and are fully incorporated here.
The teachings of Benet, Carvalho and Sestili as they relate to these claims are given previously in this office action and are fully incorporated here.
Regarding instant claims 2-7, claims of the ‘455 patent do not require the lysis solution further comprising a reducing agent of dithiothreitol (DTT), or tris(2-carboxyethyl) phosphine (TCEP) hydrochloride (instant claim 2); the lysis solution comprises 0.5-1 M urea, 0.05-0.5 % SDS, and 0.05-0.2 M TCEP (instant claims 3 and 6); the lysis solution comprises 0.5-1 M urea, 0.05-0.1 % SDS, and 0.05-0.2 M TCEP (instant claim 4); the gel contains polyacrylamide and is formed by a gel-forming solution comprising acrylamide at a concentration from 7% (w/v) to 13% (w/v) (instant claim 5); or DNA staining conducted with a staining reagent selected from a group (instant claim 7).
The teachings of Benet, Carvalho and Sestili as they relate to these claims are given previously in this office action and are fully incorporated here.
(III). Claims 1-7 and 11-13 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-13 of copending Application No. 17/643,161 (reference application) in view of Benet et al. (US 20130224737, on IDS dated 08/25/2025) in view of Carvalho et al. (Cryogel poly (acrylamide): synthesis, structure and applications.2014. Separation & Purification Reviews. 43(3): 241-262) and Sestili, et al. (The Fast-Halo Assay for the Assessment of DNA Damage at the Single-Cell Level. 2009 In: Vengrova, S., Dalgaard, J. (eds) DNA Replication. Methods in Molecular Biology, vol 521. Humana Press. p 517-533).
Although the claims at issue are not identical, they are not patentably distinct from each other because both are drawn to methods for detecting sperm DNA fragmentation (SDF) in a semen sample.
Regarding instant claim 1, copending claim 1 requires (a) embedding the semen sample containing sperm cells in a gel consisting of acrylamide and bis-acrylamide to obtain a sperm cells-embedded gel, wherein the gel has a pore size ranging from 3nm to 9nm; (b) without DNA denaturation, treating the sperm cells-embedded gel with a lysis solution to lyse the nuclear proteins of the sperm cells embedded in the gel; (c) subjecting the treated gel in step (b) to DNA staining; and (d) detecting SDF by determining the presence or the absence of a halo formation around a head of each sperm cell, wherein the presence of halo formation is indicative of the presence of a SDF and the absence of halo formation is indicative of the absence of SDF. Copending claim 2 requires the gel has a pore size ranging from 3 nm to 9 nm. Copending claim 3 requires the lysis solution includes a protein denaturant selected from the group that includes urea. Copending claim 4 requires the lysis solution includes sodium dodecyl sulfate (SDS).
Copending claims do not require the lysis solution comprises 0.5-4 M urea and 0.05-0.5% (w/v) SDS.
The teachings of Benet, Carvalho and Sestili as they relate to these claims are given previously in this office action and are fully incorporated here.
Regarding instant claims 2-6, the claims of the copending application do not require the lysis solution further comprising a reducing agent of dithiothreitol (DTT), or tris(2-carboxyethyl) phosphine (TCEP) hydrochloride (instant claim 2), the specific concentrations and combinations of urea, SDS, and TCEP as required by instant claims 3,4, and 6), or the gel contains polyacrylamide and is formed by a gel-forming solution comprising acrylamide at a concentration from 7% (w/v) to 13% (w/v) (instant claim 5).
The teachings of Benet, Carvalho and Sestili as they relate to these claims are given previously in this office action and are fully incorporated here.
Regarding instant claim 7, copending claim 13 requires DAPI staining.
Regarding instant claims 11-13, copending claim 6 requires a gel comprising acrylamides at a concentration ranging from 4% to 22% and copending claim 1 requires a gel with pore size from 3nm to 9 nm).
This is a provisional nonstatutory double patenting rejection.
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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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, WINSTON SHEN can be reached at (571)272-3157. 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.
/JESSICA GRAY/Examiner, Art Unit 1682
/WU CHENG W SHEN/Supervisory Patent Examiner, Art Unit 1682
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