CTNF 18/263,456 CTNF 80332 DETAILED ACTION Notice of Pre-AIA or AIA Status 07-03-aia AIA 15-10-aia The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA. Election/Restrictions 08-25 AIA Applicant's election with traverse of group I, claims 1-14, 16, and 19-20 in the reply filed on 03/26/2026 is acknowledged. The traversal is on the ground(s) that feature of a predigestion treatment solution comprises Tris, spermine, spermidine, EDTA, EGTA, β-mercaptoethanol, Triton-X and one or more salts from KCl, NaCl and CaCl 2 is the same technical feature in claims 19, 21, and 23. The response asserts that because the claims have unity of invention the claims can be searched and examined together . This is not found persuasive because the special technical feature that links the claims is not the technical feature that is indicated by applicant. Claim 1 does not require any of the components of the predigestion treatment solution except for EDTA. The only special technical feature linking all of the claims is EDTA as claim 1 does not require EGTA, b-mercapoethanol, Triton or a salt. The prior art teaches the special technical feature that links all of the claims, as taught by Tijssen (1993, cited on IDS) (see table 11.4) . The requirement is still deemed proper and is therefore made FINAL. 08-05 AIA Claim s 21, 23-24 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention , there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 03/26/2026 . Claims 1-14, 16, 19-20 are under examination . Claim Rejections - 35 USC § 112 07-30-02 AIA 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. 07-34-01 Claim 1-14, 16, and 19-20 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. 07-35-01 Claim 1, 3, 9, contains the trademark Cot-1 DNA. Claims 12-13, 19-20 contains the trademark/trade name Triton-X. Claim 14 contains the trade name NP-40. Where a trademark or trade name is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA), second paragraph. See Ex parte Simpson , 218 USPQ 1020 (Bd. App. 1982). The claim scope is uncertain since the trademark or trade name cannot be used properly to identify any particular material or product. A trademark or trade name is used to identify a source of goods, and not the goods themselves. Thus, a trademark or trade name does not identify or describe the goods associated with the trademark or trade name. In the present case, the trademark/trade name is used to identify/describe detergents and diagnostic reagent, accordingly, the identification/description is indefinite. Claims 2, 4-8, 10-11, 14, and 16 depend from claim 1 and are indefinite for the reasons applied to claim 1. Claim Rejections - 35 USC § 101 07-04-01 AIA 07-04 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 1-6 and 10-11 are rejected under 35 U.S.C. 101 because the claimed invention is directed to law of nature without significantly more. The claims recite are directed to a composition of matter that encompasses a law of nature. The claims recite “cot-1 DNA” which is a product of nature. Cot-1 DNA comprises genomic sequence that comprises a naturally occurring sequence and therefore encompasses a law of nature. The isolation of genomic DNA, cot-1 DNA that is identical to fragment of naturally occurring genomic DNA are naturally occurring sequences. The specification teaches cot-1 DNA is human origin (see para 37). Cot-1 is prepared from human placental DNA, purified and sheared and comprises highly repetitive DNA sequences. Cot-1 does not comprise any additional elements that are not naturally occurring. While the method of isolation comprises shearing and purifying this does not structurally change the sequence of the DNA. There is no recitation within the claims that indicate that cot-1 DNA claimed have any structural characteristic that differ from naturally occurring nucleic acids. There is no indication in the specification that the nucleic acid claimed here have any structural or functional characteristics that differ from the naturally occurring nucleic acids. Additionally the claims reciting a hybridization solution comprise EDTA, PEG, Cot-1 DNA, formamide and polyvinylpyrrolidone (PVP). These additional components do not result in a structure that is markedly different than the naturally occurring nucleic acid sequence because the solution conveys the same nucleic acid sequence. There is no indication that the hybridization solution results in changing the structure, function or other properties of the naturally occurring nucleic acid Cot-1 DNA. According the nucleic acids are a product of nature exception and the claim is directed to at least one exception. This judicial exception is not integrated into a practical application because the claims recite a sequence that is naturally occurring. The recitation of Cot-1 DNA is nothing more than an attempt to generally link the product of nature to a technological environment and is a nominal extra solution component of the claim and does not structurally change the nucleic acid sequence. The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the claims as a whole are not considered to recite any additional elements that amount to significantly more than the naturally occurring nucleotide sequences. Besides the genomic sequence Cot-1 DNA, the claims recite a composition in the preamble with an intended use and components EDTA, PEG, formamide, PVP (claim 1). Additional claims recite a solution with specific reagents. At the time the invention was made, the hybridization solution was well-established, routine and conventional. Additionally where a composition such as a hybridization solution is recited at such a high level of generality it does not meaningfully limit the claim. The recitation of claimed reagents and buffers do not structurally change the nucleic acid sequence and is not significantly more than the naturally occurring sequence. The combination of buffers and reagents of EDTA, PEG, formamide, PVP (claim 1) and the additional elements of SDS and dextran sulfate were well known, routine and conventional in the art with regard to hybridization buffers, see Mollerup (US20200340047 A1) Thus the claims as a whole does not amount to significantly more than each “product of nature” by itself and the claims do not qualify as eligible subject matter. Accordingly, it is determined that the instant claims are not directed to patent eligible subject matter. Claim Rejections - 35 USC § 102 07-06 AIA 15-10-15 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. 07-07-aia AIA 07-07 The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action: A person shall be entitled to a patent unless – 07-08-aia AIA (a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention. 07-15 AIA Claim s 1-6, 10-11, are rejected under 35 U.S.C. 102( a)(1 ) as being anticipated by Mollerup (US20200340047A1) With regard to claims 1-6, Mollerup teaches compositions for hybridization. Mollerup teaches hybridization buffer that contain one or more buffering agents, accelerating agents, chelating agents, salts, detergents, and blocking agents (see para 71). Mollerup teaches NaCl will be present at a concentration of about 600mM (claim 2-3 and 9). Mollerup teaches the buffer comprises one or more buffering agents including Tris, sodium or potassium phosphate buffer, SSC, from 1mM to about 500mM (see para 73) at near neutral pH (pH 6.8) (claims 2-39). Mollerup teaches one or more accelerating agents including BSA, polyethylene glycol, dextran sulfate and combinations thereof. Mollerup teaches the accelerating agents may be present at about 1 to about 80% (see para 74) (claim 3-4). Mollerup teaches dextran sulfate from about 5 to 15% (claim 4) (para 75). Mollerup teaches one or more chelating agents including EDTA and EGTA. Mollerup teaches concentration from .1mM to about 10mM (see para 76). Mollerup teaches one or more salts including sodium chloride, sodium phosphate and present at 10mM to 500mM (See para 77). Mollerup teaches one or more detergents including SDS and Triton at a concentration of .1 to 1% (see para 78). Mollerup teaches blocking agent including Cot1 DNA at .05mg/ml to 100 mg/ml (see para 79). With regard to claim 10-11, Mollerup teaches a hybridization solution and xylene as a dewaxing agent (claim 11), predigestion treatment solution, digestion solution, washing solution and counterstain solution (see para 134) . 07-15 AIA Claim s 19-20 are rejected under 35 U.S.C. 102( a)(1 ) as being anticipated by Trnovsky et al (US6586176) With regard to claim 19 and 20, Trnovsky et al. teaches a solution comprising 15mM Tris, 80mM KCl, 20mM NaCl, 2mM EDTA, .5mM EGTA, .2mM spermine, .5mM spermidine with .1% mercaptoethanol, and .2% Triton X-100, pH7.2 (see column 11, line 67-column 12, line 3) . Claim Rejections - 35 USC § 103 07-06 AIA 15-10-15 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. 07-20-aia AIA 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. 07-20-02-aia AIA This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention. 07-21-aia AIA Claim s 7-9 are rejected under 35 U.S.C. 103 as being unpatentable over Mollerup (US20200340047A1) in view of Tjissen (1993, cited on IDS) and Cubbage (WO96/00234, cited on IDS) Mollerup teaches compositions for hybridization. Mollerup teaches hybridization buffer that contain one or more buffering agents, accelerating agents, chelating agents, salts, detergents, and blocking agents (see para 71). Mollerup teaches NaCl will be present at a concentration of about 600mM (claim 2-3 and 9). Mollerup teaches the buffer comprises one or more buffering agents including Tris, sodium or potassium phosphate buffer, SSC, from 1mM to about 500mM (see para 73) at near neutral pH (pH 6.8) (claims 2-3). Mollerup teaches one or more accelerating agents including BSA, polyethylene glycol, dextran sulfate and combinations thereof. Mollerup teaches the accelerating agents may be present at about 1 to about 80% (see para 74) (claim 3-4). Mollerup teaches dextran sulfate from about 5 to 15% (claim 4) (para 75). Mollerup teaches one or more chelating agents including EDTA and EGTA. Mollerup teaches concentration from .1mM to about 10mM (see para 76). Mollerup teaches one or more salts including sodium chloride, sodium phosphate and present at 10mM to 500mM (See para 77). Mollerup teaches one or more detergents including SDS and Triton at a concentration of .1 to 1% (see para 78). Mollerup teaches blocking agent including Cot1 DNA at .05mg/ml to 100 mg/ml (see para 79). Mollerup teaches ranges the comprise the claimed hybridization solution ranges for NaCl, sodium citrate, EDTA, sodium phosphate buffer, Cot-1 DNA, polysucrose or sarcosine, PVP, formamide, dextran sulfate, BSA and SDS. Mollerup does not teach a specific PEG or a high molecular weight PEG. However different hybridization buffer solutions were well known in the art. Tjissen teaches hybridization buffer solutions comprising 50% formamide and 10% PEG 6000 (see Table 11.5). Cubbage teaches many different hybridization conditions are possible for in situ hybridization of biological entities. Cubbage teaches kit comprising solutions for fixation and hybridization. Cubbage teaches using 25-50% formamide, SSC, Trition-X-100 (see pg. 13, lines 22-28). Cubbage exemplifies a solution comprising PVP, EDTA, SSC, sodium phosphate buffer, Sperm DNA, PEG 3350, formamide, and Triton X-100 (see pg. 23-24). It would have been obvious to one of ordinary skill in the art at the time the invention was made to use well known high molecular weight PEG, including PEG4000 or PEG8000 in the buffer of Mollerup for the expected benefit of in situ hybridization buffer of biological entities. Mollerup teaches a buffer solution comprising PEG, Tjissen teaches a hybridization solution comprising PEG6000 and Cubbage teaches a hybridization solution comprising PEG3300, the ordinary artisan would have been a reasonable expectation of success of using a high molecular weight PEG including PEG4000 or PEG8000 because the art demonstrates the use of different high molecule weight PEG solutions for in situ hybridization buffers . 07-21-aia AIA Claim s 12-13 are rejected under 35 U.S.C. 103 as being unpatentable over Mollerup (US20200340047A1) in view of Trnovsky et al (US6586176) and Ahern (The Scientist, 1995, 20, 22) Mollerup teaches compositions for hybridization. Mollerup teaches hybridization buffer that contain one or more buffering agents, accelerating agents, chelating agents, salts, detergents, and blocking agents (see para 71). Mollerup teaches NaCl will be present at a concentration of about 600mM (claim 2-3 and 9). Mollerup teaches the buffer comprises one or more buffering agents including Tris, sodium or potassium phosphate buffer, SSC, from 1mM to about 500mM (see para 73) at near neutral pH (pH 6.8) (claims 2-3). Mollerup teaches one or more accelerating agents including BSA, polyethylene glycol, dextran sulfate and combinations thereof. Mollerup teaches the accelerating agents may be present at about 1 to about 80% (see para 74) (claim 3-4). Mollerup teaches dextran sulfate from about 5 to 15% (claim 4) (para 75). Mollerup teaches one or more chelating agents including EDTA and EGTA. Mollerup teaches concentration from .1mM to about 10mM (see para 76). Mollerup teaches one or more salts including sodium chloride, sodium phosphate and present at 10mM to 500mM (See para 77). Mollerup teaches one or more detergents including SDS and Triton at a concentration of .1 to 1% (see para 78). Mollerup teaches blocking agent including Cot1 DNA at .05mg/ml to 100 mg/ml (see para 79). Mollerup teaches biological samples comprise chromosomes (See para 52). Mollerup does not teach a solution comprising 15mM Tris, 80mM KCl, 20mM NaCl, 2mM EDTA, .5mM EGTA, .2mM spermine, .5mM spermidine with .1% mercaptoethanol, and .2% Triton X-100, pH7.2 Trnovsky et al. teaches solution for chromosomes for in situ hybridization comprising 15mM Tris, 80mM KCl, 20mM NaCl, 2mM EDTA, .5mM EGTA, .2mM spermine, .5mM spermidine with .1% mercaptoethanol, and .2% Triton X-100, pH7.2 (see column 11, line 67-column 12, line 3). Trnovsky teaches a kits and FISH hybridization solutions. Ahern teaches aspects of kits of reagents. Ahern teaches that a kit supplies all of the necessary reagents for a particular application and provides detailed instructions to follow (see pg. 20 – the kit concept). Ahern et al. teaches that packaging reagents in kit format is convenient, offering the scientist the opportunity to better manage their time. Ahern et al. teach that premade reagents and packaged kits saves researchers time (see page 4 and 5). It would have been obvious to one of ordinary skill in the art at the time the invention was made to include well-known chromosome buffer solution as taught by Trnovsky with the hybridization buffer solution for chromosome FISH as taught by Mollerup and package the buffer solutions in kit form as taught by Trnovsky for improving efficiency. The ordinary artisan would have been motivated to include both buffer solution of Trnovsky and Mollerup in kit form in a packaged kit because kits all for convenient format and premade reagents save researchers time as taught by Ahern . 07-21-aia AIA Claim s 14 and 16 are rejected under 35 U.S.C. 103 as being unpatentable over Mollerup (US20200340047A1) in view of Ahern (The Scientist, 1995, pg. 20, 22) and Remstein (Br. J. Haematology, 2000, vol 110, pp 856-862) . Mollerup teaches compositions for hybridization. Mollerup teaches hybridization buffer that contain one or more buffering agents, accelerating agents, chelating agents, salts, detergents, and blocking agents (see para 71). Mollerup teaches NaCl will be present at a concentration of about 600mM (claim 2-3 and 9). Mollerup teaches the buffer comprises one or more buffering agents including Tris, sodium or potassium phosphate buffer, SSC, from 1mM to about 500mM (see para 73) at near neutral pH (pH 6.8) (claims 2-3). Mollerup teaches one or more accelerating agents including BSA, polyethylene glycol, dextran sulfate and combinations thereof. Mollerup teaches the accelerating agents may be present at about 1 to about 80% (see para 74) (claim 3-4). Mollerup teaches dextran sulfate from about 5 to 15% (claim 4) (para 75). Mollerup teaches one or more chelating agents including EDTA and EGTA. Mollerup teaches concentration from .1mM to about 10mM (see para 76). Mollerup teaches one or more salts including sodium chloride, sodium phosphate and present at 10mM to 500mM (See para 77). Mollerup teaches one or more detergents including SDS and Triton at a concentration of .1 to 1% (see para 78). Mollerup teaches blocking agent including Cot1 DNA at .05mg/ml to 100 mg/ml (see para 79). Mollerup teaches biological samples comprise chromosomes (See para 52). Mollerup does not teach a solution comprising pepsin and HCl and a solution comprising NaCl, trisodium citrate, and NP-40 or a solution comprising DAPI, and a fixative solution of ethanol. However, Remstein teaches fluorescence in situ hybridization. Remstein teaches solutions for FISH include pepsin with HCl, SSC solution and SSC/Nonidet 40 (NaCl and Na 3 C 6 H 5 O 7 ) (see pg. 857, 2 nd column). Remstein teaches counterstaining solution comprising DAPI (see pg. 857, 2 nd column). Remstein teaches solutions comprising ethanol (see pg. 857, end column). Ahern teaches aspects of kits of reagents. Ahern teaches that a kit supplies all of the necessary reagents for a particular application and provides detailed instructions to follow (see pg. 20 – the kit concept). Ahern et al. teaches that packaging reagents in kit format is convenient, offering the scientist the opportunity to better manage their time. Ahern et al. teach that premade reagents and packaged kits saves researchers time (see page 4 and 5). It would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made to have combined the hybridization buffer solution taught by Mollerup with the fixing, washing and counterstaining solutions of Remstein into a kit comprising each of the solutions for FISH as taught by Ahern et al. One would have been motivated to do include the solutions of Remstein with the hybridization solution of Mollerup because both Mollerup and Remstein teach solutions for FISH and one would have included each of the solutions in a kit based on the assertion of Ahern that kits of packaged reagents are convenient and save time (see pg. 20). Conclusion No claims are allowable. Any inquiry concerning this communication or earlier communications from the examiner should be directed to SARAE L BAUSCH whose telephone number is (571)272-2912. The examiner can normally be reached M-F 9a-4p. 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, Fereydoun Sajjadi can be reached at 571-272-3311. 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. /SARAE L BAUSCH/Primary Examiner, Art Unit 1699 Application/Control Number: 18/263,456 Page 2 Art Unit: 1699 Application/Control Number: 18/263,456 Page 3 Art Unit: 1699 Application/Control Number: 18/263,456 Page 4 Art Unit: 1699 Application/Control Number: 18/263,456 Page 5 Art Unit: 1699 Application/Control Number: 18/263,456 Page 6 Art Unit: 1699 Application/Control Number: 18/263,456 Page 7 Art Unit: 1699 Application/Control Number: 18/263,456 Page 8 Art Unit: 1699 Application/Control Number: 18/263,456 Page 9 Art Unit: 1699 Application/Control Number: 18/263,456 Page 10 Art Unit: 1699 Application/Control Number: 18/263,456 Page 11 Art Unit: 1699 Application/Control Number: 18/263,456 Page 12 Art Unit: 1699 Application/Control Number: 18/263,456 Page 13 Art Unit: 1699
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