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 17/643,161 filed 12/07/2021 claims the priority to Taiwanese Application No:109145792, filed 12/23/2020.
Receipt of a certified English translation of the priority document TW No. 109145792 filed on 08/20/2025 is acknowledged and foreign priority is perfected.
The priority date of claim 1 and its dependent claims is determined to be 12/23/2020, the filing date of Taiwanese Application No:109145792.
Status of Claims
Applicant’s amendments to claims filed 08/20/2025 in response to the Non-Final Rejection mailed 05/21/2025 are acknowledged.
Claims 1 and 6 are amended.
Claims 1-17 are pending and claims 1-13 are under examination.
Election/Restrictions
Applicant elected without traverse Group I, claims 1-13, in the reply filed on 03/28/2025.
Response to Remarks filed 08/20/2025
The amendments and arguments presented in the papers filed 08/20/2025 ("Remarks”) have been thoroughly considered. The issues raised in the Office action dated 03/28/2025 listed below have been reconsidered as indicated.
a) The rejection of claims 1-13 under 35 U.S.C. 101 are withdrawn in view of the amendments to the claims.
c) The rejection of claims 1 and 3-5 under 35 U.S.C. 102 as being anticipated by Benet et al. (US 20130224737) are withdrawn in view of the amendments to the claims.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 and 3-5 are rejected under 35 U.S.C. 103 as being unpatentable over Benet et al. (US 20130224737, on IDS dated 01/24/2022) in view of 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).
This is a new rejection as necessitated by the claim amendments.
Regarding claim 1, Benet teaches a method for determining the presence of cells that contain ROS (reactive oxygen species) 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 acrylic acid, polyacrylamide, N-isopropylacrylamide and alginate (paras 50-58). Benet teaches the method further comprises treating the sample with 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 treatment with an acid denaturation step and does not teach performing the method without denaturation as in step (b) or that the absence of halo formation is indicative of the absence of SDF in step (d).
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 and Sestili to arrive at the instantly claimed invention. The modification would have entailed using the denaturing conditions of Sestili in the method of Benet. One would have been motivated by the improved 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. 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, Benet teaches a lysis solution can contain a chaotropic agent (i.e. protein denaturant) (para 79) such as urea (para 80).
Regarding claim 4, Benet teaches a lysis solution can contain a detergent (i.e. ionic surfactant) such as sodium lauryl sulfate (para 79).
Regarding claim 5, Benet teaches a DNA probe (i.e. stain) that is preferably DAPI (para 82).
Claim 2 and 6-13 are rejected under 35 U.S.C. 103 as being unpatentable over Benet et al. (US 20130224737, on IDS dated 01/24/2022) 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) as applied to claims 1 and 3-5 above, and further in view of Chrambach et al. (Polyacrylamide Gel Electrophoresis.1971. Science, 172: 440-451).
These are modified rejections as necessitated by the claim amendments.
The teachings of Benet and Sestili as they relate to claim 1 are stated in the 103 rejection above in this office action.
Regarding claim 2, neither Benet nor Sestili teach a pore size ranging from 3 nm to 9 nm.
Chrambach teaches pore sizes that include pores with a radius between 1.5nm and 3.5nm, thus satisfying a limitation or a pore size (diameter) between 3nm and 7 nm as required by claim 2 (p. 443, Figure 3).
Chrambach teaches that pore sizes can be selected for optimal resolution between any two species (p. 440, col 3).
It would have been prima facie obvious to one with ordinary skill in the art before the effective filing date of the claimed invention to have used the pore sizes of Chrambach in the gels of Benet and Sestili to arrive at the instantly claimed invention. Differences in pore size are routine optimizations known in the art. 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.
Regarding claim 6, Benet teaches a method for determining the presence of cells that contain ROS (reactive oxygen species) 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 acrylic acid, polyacrylamide, N-isopropylacrylamide and alginate (paras 50-58). Benet teaches the method further comprises treating the sample with 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 treatment with an acid denaturation step and does not teach performing the method without denaturation as in step (b) or that the absence of halo formation is indicative of the absence of SDF in step (d).
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 and Sestili to arrive at the instantly claimed invention. The modification would have entailed using the denaturing conditions of Sestili in the method of Benet. One would have been motivated by the improved 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. 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.
Neither Benet nor Sestili teach a polyacrylamide gel containing acrylamide at a concentration ranging from 3% (w/v, g/mL) to 22% (w/v, g/mL) as recited in claim 6, step (b).
Chrambach teaches polyacrylamide gel concentrations ranging from 6.5-20% (p. 443, Figure 3). The appendix on p 10 defines T as used in figure 3 as the total gel concentration (w/v) as required in claim 6 step (b).
Chrambach teaches that pore sizes can be selected for optimal resolution between any two species and further that the pore size can be controlled by adjusting total concentration and concentration of a crosslinking agent (i.e. bis-acrylamide) (p. 440, col 3).
It would have been prima facie obvious to one with ordinary skill in the art before the effective filing date of the claimed invention to have used the polyacrylamide concentrations of Chrambach in the gels of Benet and Sestili to arrive at the instantly claimed invention. Differences in concentration are routine optimizations known in the art. 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 by varying total acrylamide concentration as in Chrambach to find conditions that provided optimal resolution between fragmented and non-fragmented DNA.
Regarding claims 7-10, neither Benet nor Sestili teach the polyacrylamide gel contains acrylamide at a concentration ranging from 4% (w/v, g/mL) to 22% (w/v, g/mL) (claim 7); the polyacrylamide gel has a pore size ranging from 3nm to 10nm (claim 8); the polyacrylamide gel is formed from acrylamide and bis-acrylamide ranging from 19:1 (w/w) to 199:1 (w/w) (claim 9); or the polyacrylamide gel is formed from acrylamide and bis-acrylamide ranging from 24:1 (w/w) to 99:1 (w/w) (claim 10)
Regarding claim 7, Chrambach teaches polyacrylamide gel concentrations ranging from 6.5-20% (p. 443, Figure 3). The appendix on p 10 defines T as used in figure 3 as the total gel concentration (w/v) as required in claim 7.
Regarding claim 8, Chrambach teaches polyacrylamide gels with pore sizes that include pores with a radius between 1.5nm and 3.5nm, thus satisfying a limitation or a pore size (diameter) between 3nm and 7nm as required by claim 2 (p. 443, Figure 3).
Regarding claim 9, Chrambach teaches % C ranges of 1-25% (p. 443, Figure 3). The Appendix on p. 449 defines C as used in figure 3 as the % cross-linking using Bis (i.e. bis-acrylamide, w/v as in the Appendix) and acrylamide. Thus the %C values in Figure 3 include ratios of 19:1 acrylamide to bis-acrylamide (5%C) as required in claim 9.
Regarding claim 10, Chrambach teaches % C ranges of 1-25% (p. 443, Figure 3). The Appendix on p. 449 defines C as used in figure 3 as the % cross-linking using Bis (i.e. bis-acrylamide, w/v as in the Appendix) and acrylamide. Thus the %C values in Figure 3 include ratios of 29:1 acrylamide to bis-acrylamide (3.3%C) as required in claim 9.
Chrambach teaches that pore sizes can be selected for optimal resolution between any two species and further that the pore size can be controlled by adjusting total concentration and concentration of a crosslinking agent (i.e. bis-acrylamide) (p. 440, col 3).
It would have been prima facie obvious to one with ordinary skill in the art before the effective filing date of the claimed invention to have used the polyacrylamide concentrations, pore size range and acrylamide: bis-acrylamide ratios of Chrambach in the gels of Benet and Sestili to arrive at the instantly claimed invention. Differences in concentration are routine optimizations known in the art. 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 by varying total acrylamide concentration and acrylamide to bi-acrylamide ratios as in Chrambach to find conditions that provided optimal resolution between fragmented and non-fragmented DNA.
Regarding claim 11, Benet teaches a lysis solution can contain a chaotropic agent (i.e. protein denaturant) (para 79) such as urea (para 80).
Regarding claim 12, Benet teaches a lysis solution can contain a detergent (i.e. ionic surfactant) such as sodium lauryl sulfate (para 79).
Regarding claim 13, Benet teaches a DNA probe (i.e. stain) that is preferably DAPI (para 82).
Response to Arguments against Claim Rejections – previous 35 U.S. C § 102
The response asserts the following differences between the instant claims and Benet: (1) In Benet, the sample is denatured to single-stranded (ss) DNA, whereas the present claims requires that the sample is not treated by DNA denaturation and (2) In Benet, no halo means SDF (sperm DNA fragmentation), whereas in the present claims, no halo means without SDF (p. 6-7)
Applicant’s arguments with respect to the rejection(s) of claim(s) 1 and 3-5 under 35 U.S. C § 102 have been fully considered and are persuasive. Therefore, the rejection has been withdrawn. However, upon further consideration, a new ground(s) of rejection is made over Benet in view of Sestili as described above in the new rejections of the claims.
The response presents Table 1, page 22 of the applicant’s specification for support in their argument (p. 5) as well as sections and figures from the specification (p. 7-8).
In response to applicant's argument that the references fail to show certain features of the invention, it is noted that the features upon which applicant relies (i.e., Table 1, Figure 2 and supporting paragraphs and figures of the specification) are not recited in the rejected claim(s). Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993).
Response to Arguments against Claim Rejections – previous 35 U.S. C § 103
In regards to claims 1, 2, and 6-13, the response asserts that Chrambach only discloses polyacrylamide pore sizes and addition of Chrambach does not cure the deficiencies of Benet and requests that the rejections should be overcome(p. 9).
Applicant's arguments have been fully considered but are not persuasive.
In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
Modified rejections are presented here. The teachings of Chrambach combined with the teachings of Benet and Sestili as described above satisfy the requirements of claims 1, 2, and 6-13.
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.
These are new rejections necessitated by the amendments to the claims.
(I).(i). Claims 1, 3 and 4 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 01/24/2022) in view of 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 patent ‘455 discloses a method for detecting sperm DNA fragmentation in a semen sample.
Claims 1, 7, and 13 of the ‘455 patent require elements of a method that satisfy the requirements of instant claim 1.
Claim 1 of the ‘455 patent requires (a) embedding the semen sample containing semen cells in a gel comprising agarose, acrylamide, alginate, or vinyl chloride; 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, wherein the presence of a halo having a halo width smaller than one third of a diameter of the corresponding sperm head is indicative of presence of sperm DNA fragmentation. Claim 7 of the ‘455 patent requires (a) adding a semen sample containing sperm cells to 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 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, wherein the presence of a halo having a halo width smaller than one third of a diameter of the corresponding sperm head is indicative of presence of sperm DNA fragmentation. Claim 13 of the ‘455 patent requires: (a) admixing a semen sample containing sperm cells with a gel-forming component, followed a gel polymerization reaction, so as to obtain a gel with the sperm cells containing denatured DNA embedded within, the gel-forming component being selected from the group consisting of acrylamide, alginate, and vinyl chloride; (b) subjecting the gel to a lysis treatment with a lysis solution to lyse the nuclear proteins of the sperm cells embedded in the gel; (c) subjecting the lysed gel obtained in step (b) to DNA staining; and (d) observing the presence or the absence of halo formation around heads of the sperm cells, wherein the presence of a halo having a halo width smaller than one third of a diameter of the corresponding sperm head is indicative of presence of sperm DNA fragmentation.
Thus claims 1, 7, and 13 of the ‘455 patent require elements of a method that encompass the instant claim 1.
However, regarding instant claim 1, claims 1, 7, and 13 of the ‘455 patent do not require a step without DNA denaturation (step (b)), or the absence of halo formation is indicative of the absence of SDF.
The teachings of Sestili as they relate to this claim is given previously in this office action and are fully incorporated here.
Regarding instant claim 3, claims 5,11, and 17 of the ‘455 patent requires the lysis solution further includes a protein denaturant of 3-[(3-cholamidopropyl) dimethylammonio]-1-propanesulfonate hydrate, guanidinium chloride, or a combination thereof.
Regarding instant claim 4, claims 6, 12, and 18 of the ‘455 patent require the lysis solution further includes an ionic surfactant selected from the group consisting of sodium deoxycholate, sodium cholate, sodium lauroyl sarcosinate, and combinations thereof.
(ii). Claims 2 and 6- 12 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 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) and Chrambach et al. (Polyacrylamide Gel Electrophoresis.1971. Science, 172: 440-451).
Regarding instant claim 2, Patent 11,644,455 does not require a gel with a pore size of 3nm to 9nm.
The teachings of Chrambach and Sestili as they relate to this claim are given previously in this office action and are fully incorporated here.
Regarding instant claim 6, claims 1, 7, and 13 of the ‘455 patent require the elements encompassed by the instant claim.
Claim 1 of the ‘455 patent requires (a) embedding the semen sample containing semen cells in a gel comprising agarose, acrylamide, alginate, or vinyl chloride; 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, wherein the presence of a halo having a halo width smaller than one third of a diameter of the corresponding sperm head is indicative of presence of sperm DNA fragmentation. Claim 7 of the ‘455 patent requires (a) adding a semen sample containing sperm cells to 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 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, wherein the presence of a halo having a halo width smaller than one third of a diameter of the corresponding sperm head is indicative of presence of sperm DNA fragmentation. Claim 13 of the ‘455 patent requires: (a) admixing a semen sample containing sperm cells with a gel-forming component, followed a gel polymerization reaction, so as to obtain a gel with the sperm cells containing denatured DNA embedded within, the gel-forming component being selected from the group consisting of acrylamide, alginate, and vinyl chloride; (b) subjecting the gel to a lysis treatment with a lysis solution to lyse the nuclear proteins of the sperm cells embedded in the gel; (c) subjecting the lysed gel obtained in step (b) to DNA staining; and (d) observing the presence or the absence of halo formation around heads of the sperm cells, wherein the presence of a halo having a halo width smaller than one third of a diameter of the corresponding sperm head is indicative of presence of sperm DNA fragmentation.
However, regarding instant claim 6, claims ‘455 patent do not require a polyacrylamide gel containing acrylamide at a concentration ranging from 3% (w/v, g/mL) to 22% (w/v, g/mL) (claim 6, step (a)); a step without DNA denaturation (step (b)), or the absence of halo formation is indicative of the absence of SDF (step d).
The teachings of Sestili and Chrambach as they relate to this claim is given previously in this office action and are fully incorporated here.
Regarding instant claims 7-10, claims of the ‘455 patent do not require a polyacrylamide gel that contains acrylamide at a concentration ranging from 4% (w/v, g/mL) to 22 % (w/v, g/mL) (claim 7); polyacrylamide gel with a pore size of 3nm to 10nm (instant claim 8); polyacrylamide gel is formed from acrylamide and bis-acrylamide in a ratio of acrylamide to bis-acrylamide ranging from 19:1 (w/w) to 199:1 (w/w) (claim 9); or ratio of acrylamide to bis-acrylamide ranging from 24:1 (w/w) to 99:1 (w/w) (claim 10).
The teachings of Chrambach as they relate to this claim is given previously in this office action and are fully incorporated here.
Regarding instant claim 11, claims 5, 11, and 17 of the ‘455 patent require the lysis solution further includes a protein denaturant of 3-[(3-cholamidopropyl) dimethylammonio]-1-propanesulfonate hydrate, guanidinium chloride, or a combination thereof.
Regarding instant claim 12, claims 6, 12, and 18 of the ‘455 patent require the lysis solution further includes an ionic surfactant selected from the group consisting of sodium deoxycholate, sodium cholate, sodium lauroyl sarcosinate, and combinations thereof.
(iii). Claims 5, and 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 01/24/2022).
Patent 11,644,455 does not require DNA staining conducted with a staining reagent selected from a group (claims 5 and 13).
The teachings of Benet as they relate to these claims are given previously in this office action and are fully incorporated here.
(II). (i). Claims 1, 3, and 4 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 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 patented claims are species claims that anticipate the genus claims of the instant application.
Claims 1, 7, and 13 of the ‘039 patent require elements of a method that satisfy the requirements of instant claim 1.
Regarding instant claim 1, claim 1 of the ‘039 patent requires (a) embedding the semen sample containing semen cells in a gel comprising agarose; (b) subjecting the sperm cells-embedding gel to a DNA denaturation treatment with a DNA denaturing solution, to denature the DNA of the sperm cells; (c) subjecting the denatured gel obtained in step (b) to a lysis treatment with a lysis solution including urea 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) to lyse the nuclear proteins of the sperm cells; (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, wherein no halo formation or the presence of a halo having a halo width smaller than one third of a diameter of the corresponding sperm head is indicative of presence of sperm DNA fragmentation. Claim 7 of the ‘039 patent requires (a) heating an agarose solution, followed by adding a DNA denaturing solution comprising HCl and 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 0.5M to 4M 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, wherein no halo formation or the presence of a halo having a halo width smaller than one third of a diameter of the corresponding sperm head is indicative of presence of sperm DNA fragmentation. Claim 13 of the ‘039 patent requires (a) admixing a semen sample containing sperm cells with a DNA denaturing solution and a gel-forming component of acrylamide, followed by subjecting a mixture thus obtained to a gel polymerization reaction, so as to obtain a gel with the sperm cells containing denatured DNA embedded within;(b) subjecting the gel to a lysis treatment with a lysis solution including 0.5M to 4M urea and 0.05% to 0.5% (w/v) sodium dodecyl sulfate, to lyse the nuclear proteins of the sperm cells embedded in the gel;(c) subjecting the lysed gel obtained in step (b) to DNA staining; and(d) observing the presence or the absence of halo formation around heads of the sperm cells, wherein no halo formation or the presence of a halo having a halo width smaller than one third of a diameter of the corresponding sperm head is indicative of presence of sperm DNA fragmentation.
Thus claims 1, 7, and 13 of the ‘309 patent require elements of a method that encompass the instant claim 1.
However, claims of the ‘039 patent do not require a step without DNA denaturation (step (b)), or the absence of halo formation is indicative of the absence of SDF (step d).
The teachings of Sestili as they relate to this claim is given previously in this office action and are fully incorporated here.
Regarding instant claim 3, claims 1,3, and 17 of the ‘039 patent require a lysis solution that further includes a protein denaturant of 3-[(3cholamidopropyl) dimethyl-ammonio]-1-propanesulfonate hydrate, guanidinium chloride, or a combination thereof.
Regarding instant claim 4, claims 6, 11, and 18 of the ‘039 patent require the lysis solution further includes an ionic surfactant selected from the group consisting of sodium deoxycholate, sodium cholate, sodium lauroyl sarcosinate, and combinations thereof.
(ii). Claims 2 and 6-12 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 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) and Chrambach et al. (Polyacrylamide Gel Electrophoresis.1971. Science, 172: 440-451).
Regarding instant claim 2, Patent 11,644,455 does not require a gel with a pore size of 3nm to 9nm.
The teachings of Chrambach and Sestili as they relate to this claim are given previously in this office action and are fully incorporated here.
Regarding instant claim 6, claims 1, 7, and 13 of the ‘039 patent require the elements encompassed by the instant claim.
Regarding instant claim 6, claim 1 of the ‘039 patent requires a method comprising: (a) embedding the semen sample containing semen cells in a gel comprising agarose; (b) subjecting the sperm cells-embedding gel to a DNA denaturation treatment with a DNA denaturing solution, to denature the DNA of the sperm cells; (c) subjecting the denatured gel obtained in step (b) to a lysis treatment with a lysis solution including urea 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) to lyse the nuclear proteins of the sperm cells; (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, wherein no halo formation or the presence of a halo having a halo width smaller than one third of a diameter of the corresponding sperm head is indicative of presence of sperm DNA fragmentation.
Claim 7 of the ‘039 patent requires a method comprising: (a) heating an agarose solution, followed by adding a DNA denaturing solution comprising HCl and 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 0.5M to 4M 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, wherein no halo formation or the presence of a halo having a halo width smaller than one third of a diameter of the corresponding sperm head is indicative of presence of sperm DNA fragmentation. Claim 13 of the ‘039 patent requires a method comprising: (a) admixing a semen sample containing sperm cells with a DNA denaturing solution and a gel-forming component of acrylamide, followed by subjecting a mixture thus obtained to a gel polymerization reaction, so as to obtain a gel with the sperm cells containing denatured DNA embedded within;(b) subjecting the gel to a lysis treatment with a lysis solution including 0.5M to 4M urea and 0.05% to 0.5% (w/v) sodium dodecyl sulfate, to lyse the nuclear proteins of the sperm cells embedded in the gel;(c) subjecting the lysed gel obtained in step (b) to DNA staining; and(d) observing the presence or the absence of halo formation around heads of the sperm cells, wherein no halo formation or the presence of a halo having a halo width smaller than one third of a diameter of the corresponding sperm head is indicative of presence of sperm DNA fragmentation.
However, regarding instant claim 6, claims ‘455 patent do not require a polyacrylamide gel containing acrylamide at a concentration ranging from 3% (w/v, g/mL) to 22% (w/v, g/mL) (claim 6, step (a)); a step without DNA denaturation (step (b)), or the absence of halo formation is indicative of the absence of SDF (step d).
The teachings of Sestili and Chrambach as they relate to this claim is given previously in this office action and are fully incorporated here.
Regarding instant claims 7-10, claims of the ‘039 patent do not require a gel with a pore size of 3nm to 9nm (instant claim 2); a polyacrylamide gel that contains acrylamide at a concentration ranging from 4% (w/v, g/mL) to 22 % (w/v, g/mL) (claim 7); polyacrylamide gel with a pore size of 3nm to 10nm (instant claim 8); polyacrylamide gel is formed from acrylamide and bis-acrylamide in a ratio of acrylamide to bis-acrylamide ranging from 19:1 (w/w) to 199:1 (w/w) (claim 9); or ratio of acrylamide to bis-acrylamide ranging from 24:1 (w/w) to 99:1 (w/w) (claim 10).
The teachings of Chrambach as they relate to these claims are given previously in this office action and are fully incorporated here.
Regarding instant claim 11, claims 1,3, and 17 of the ‘039 patent require a lysis solution that further includes a protein denaturant of 3-[(3-cholamidopropyl) dimethylammonio]-1-propanesulfonate hydrate, guanidinium chloride, or a combination thereof.
Regarding instant claim 12, claims 6, 11, and 18 of the ‘039 patent require the lysis solution further includes an ionic surfactant selected from the group consisting of sodium deoxycholate, sodium cholate, sodium lauroyl sarcosinate, and combinations thereof.
(iii). Claims 5 and 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 01/24/2022).
Patent 12,153,039 does not require DNA staining conducted with a staining reagent selected from a group (claims 5 and 13).
The teachings of Benet as they relate to these claims are given previously in this office action and are fully incorporated here.
Response to Arguments against Double Patenting
The response asserts that the pending claims are different from and not an obvious variation of the claims in U.S. Patent No. 11,644,455 (p. 10) and that the pending claims are different from and not an obvious variation of the claims in U.S. Patent No. 12,153,039).
Applicant's arguments have been fully considered but are not persuasive.
The double patenting rejections have been modified to reflect the new and modified grounds of rejection under USC 103 for obviousness. as described above in the modified double patenting rejections of the claims.
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