DETAILED ACTION
Notice of Pre-AIA or AIA Status
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
2. This action is in response to the papers filed June 16, 2026. Applicant’s remarks and amendments have been fully and carefully considered but are not found to be sufficient to put the application in condition for allowance. Any new grounds of rejection presented in this Office Action are necessitated by Applicant's amendments. Any rejections or objections not reiterated herein have been withdrawn. This action is made FINAL.
3. Applicant’s election without traverse of Group II in the reply filed on March 30, 2026 is reiterated for the record.
Claims 1-9 are currently pending.
Claims 1-3 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on March 30, 2026.
Nucleotide and/or Amino Acid Sequence Disclosures
4. Summary of Requirements for Patent Applications Filed On Or After July 1, 2022, That Have Sequence Disclosures
37 CFR 1.831(a) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.831(b) must contain a “Sequence Listing XML”, as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.831-1.835. This “Sequence Listing XML” part of the disclosure may be submitted:
1. In accordance with 37 CFR 1.831(a) using the symbols and format requirements of 37 CFR 1.832 through 1.834 via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter “Legal Framework”) in XML format, together with an incorporation by reference statement of the material in the XML file in a separate paragraph of the specification (an incorporation by reference paragraph) as required by 37 CFR 1.835(a)(2) or 1.835(b)(2) identifying:
a. the name of the XML file
b. the date of creation; and
c. the size of the XML file in bytes; or
2. In accordance with 37 CFR 1.831(a) using the symbols and format requirements of 37 CFR 1.832 through 1.834 on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation by reference statement of the material in the XML format according to 37 CFR 1.52(e)(8) and 37 CFR 1.835(a)(2) or 1.835(b)(2) in a separate paragraph of the specification identifying:
a. the name of the XML file;
b. the date of creation; and
c. the size of the XML file in bytes.
SPECIFIC DEFICIENCIES AND THE REQUIRED RESPONSE TO THIS NOTICE ARE AS FOLLOWS:
Specific deficiency - This application fails to comply with the requirements of 37 CFR 1.831-1.834 because it does not contain a “Sequence Listing XML” as a separate part of the disclosure. A “Sequence Listing XML” is required because claim 9 has been amended such that it now recites an amino acid sequence.
Required response - Applicant must provide:
• A “Sequence Listing XML” part of the disclosure, as described above in item 1. or 2.; together with
o A statement that indicates the basis for the amendment, with specific references to particular parts of the application as originally filed, as required by 37 CFR 1.835(a)(3);
o A statement that the “Sequence Listing XML” includes no new matter as required by 37 CFR 1.835(a)(4)
AND
• A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3), and 1.125 inserting the required incorporation by reference paragraph as required by 37 CFR 1.835(a)(2), consisting of:
o A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
o A copy of the amended specification without markings (clean version); and
o A statement that the substitute specification contains no new matter.
Claim Rejections - 35 USC § 112(a)
5. The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claim 9 is rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention. This is a new matter rejection.
In the instant case the specification does not appear to provide support for the amendment which recites the following limitation:
a polypeptide having the amino acid sequence MAEIGTGFPFDPHYVEVLGERMHYVDVGPRDGTPVLFLHGNPTSSYVWRNIIPHVAPSH RCIAPDLIGMGKSDKPDLDYFFDDHVRYLDAFIEALGLEEVVLVIHDWGSALGFHWAKR NPERVKGIACMEFIRPIPTWDEWPEFARETFQAFRTADVGRELIDQNAFIEGALPMGVVR PLTEVEMDHYREPFLKPVDREPLWRFPNELPIAGEPANIVALVEAYMNWLHQSPVPKLL FWGTPGVLIPPAEAARLAESLPNCKTVDIGPGLFLLQEDNPDLIGSEIARWLPGQA
It is noted that in the remarks filed on June 16, 2026, the Applicants state that claim 9 has been amended to replace “a halotag” with the specific amino acid sequence of the polypeptide. However it is noted for the record that while all HaloTags consist of a modified version of the bacterial enzyme haloalkane dehalogenase (about 297 amino acids and roughly 34 kDa in size), several versions have been engineered over time. The prior art of Buckley (Angew Chem Int Ed 2014 53 pages 2312-2330) teaches that owing in large part to stability issues associated with HaloTag2, the company Promega has continued to optimize the HaloTag system to increase the stability and decrease the propensity for aggregation of the fusion proteins. Their result was the HaloTag7 protein, which contains 22 point mutations with respect to HaloTag2 (page 2323, col 1). Thus while the specification discloses HaloTags, not all HaloTags have the same sequence. Since there is no specific support in the specification for the amino acid sequence set forth in claim 9, the claim is rejected for containing new matter.
Claim Rejections - 35 USC § 112(b)
6. 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 4-9 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.
Regarding Claims 4-6 and 9 it is not clear how the recited preamble is intended to breathe life and meaning into the claim. The preamble of the claim recites a method for identifying and/or quantifying in a sample the DNA damage events associated to actively transcribed genomic loci, yet the method only requires comprising detecting a CDK12 protein in proximity of these genomic loci. Thus it is not clear if applicant intends to cover only a method of detecting a CDK12 protein in proximity to a DNA damage event OR if the method is intended to somehow require more to accomplish the goal set forth in the preamble. If it is the later, then it appears that the claims are incomplete, as they fail to provide any active steps that clearly accomplish the goal set forth by the preamble of the claims. The claims as amended recite “wherein the presence of the CDK12 protein identifies DNA damage events associated with actively transcribed genomic loci”. However, Applicants are reminded that claim scope is not limited by claim language (such as wherein clauses) that suggests or makes optional but does not require steps to be performed.
Response To Arguments
7. In the response the Applicants traversed the rejections under 35 USC 112(b). In response to the question how the recited preamble is intended to breathe life and meaning into the claim, the Applicants state that claim 4 has been amended to recite “wherein the presence of the CDK12 protein identifies DNA damage events associated with actively transcribed genomic loci”. The Applicants argue that this language clarifies the functional relationship between the detection step and the identification of the relevant class of DNA damage events.
The amendment has been fully considered but does not overcome the rejection. Applicants are reminded that claim scope is not limited by claim language (such as wherein clauses) that suggests or makes optional but does not require steps to be performed. This rejection could be overcome by amending the claims to recite an active process step that accomplishes the goal set forth by the preamble.
Claim Rejections - 35 USC § 101
8. 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 4-9 are rejected under 35 U.S.C. 101 because the claimed invention is directed to judicial exception without significantly more. The claims recite a judicial exception that is not integrated into a practical application. The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception. The claim analysis is set forth below.
Step 1: The claims are directed to the statutory category of a process.
Step 2A, prong one: Evaluate Whether the Claim Recites a Judicial Exception
The instant claims recite a law of nature.
The claims recite “wherein the presence of the CDK12 protein identifies DNA damage events associated with actively transcribed genomic loci”. The claims as amended recite a correlation between the presence of CDK12 protein in proximity to actively transcribed genomic loci and DNA damage events. This type of correlation is a consequence of natural processes, similar to the naturally occurring correlation found to be a law of nature by the Supreme Court in Mayo.
Step 2A, prong two: Evaluate Whether the Judicial Exception Is Integrated Into a Practical Application
The claims do NOT recite additional steps or elements that integrate the recited judicial exceptions into a practical application of the exception(s). For example, the claims do not practically apply the judicial exception by including one or more additional elements that the courts have stated integrate the exception into a practical application:
An additional element reflects an improvement in the functioning of a computer, or an improvement to other technology or technical field;
An additional element that applies or uses a judicial exception to effect a particular treatment or prophylaxis for a disease or medical condition;
An additional element implements a judicial exception with, or uses a judicial exception in conjunction with, a particular machine or manufacture that is integral to the claim;
An additional element effects a transformation or reduction of a particular article to a different state or thing; and
An additional element applies or uses the judicial exception in some other meaningful way beyond generally linking the use of the judicial exception to a particular technological
environment, such that the claim as a whole is more than a drafting effort designed to monopolize the exception.
In addition to the judicial exception the claims recite a step of “detecting” a CDK12 protein in proximity to actively transcribed genomic loci. Claims 6-9 are directed to methods of detection. The “detecting” does NOT integrate the judicial exception into a practical application because it merely adds insignificant extra-solution activity (data gathering) to the judicial exception.
Step 2B: Evaluate Whether the Claim Provides an Inventive Concept
In addition to the judicial exception the claims recite a step of “detecting” a CDK12 protein in proximity to actively transcribed genomic loci. Claims 6-9 are directed to methods of detection. The “detecting” does NOT amount to significantly more because it simply appends well understood, routine, and conventional activities previously known in the art, specified at a high level of generality, to the judicial exceptions.
The “detecting” step in claim 4 is recited at a high level of generality. It merely instructs a scientist to use any detection technique. When recited at this high level of generality, there is no meaningful limitation that distinguishes this step from well understood, routine, and conventional activities engaged in by scientists prior to applicants invention and at the time the application was filed.
Additionally the teachings in the specification demonstrate the well understood, routine, conventional nature of additional elements because it teaches that the additional elements are well known or commercially available. For example the specification teaches the following detection methods:
Antibody-Based Detection
[0070] The procedure is based on established protocols for antibody-based detection of cell epitopes in cells and tissues, using standard immunofluorescence or immunohistochemistry methods.
2. Antibody-Based Detection (Dual-Markers, PLA-Assay)
[0078] This procedure is based on the method called proximity ligation assay (PLA-assay), a procedure that uses antibody-based technology and PCR to visualize the physical proximity of biomolecules.
3. Antibody-Free Detection (Detection Based on Labelled CDK12)
[0087] Cells or tissues can be engineered to express chimeric proteins derived from the fusion of CDK12-CDNA with a protein-based fluorescent marker such as a fluorescent protein (mCHERRY, RFP, EGFP, EYP, others . . . ) or HaloTAG. This allows the direct visualization of CDK12 recruitment to DNA-damaged transcribed loci.
The prior art also demonstrates the well understood, routine, conventional nature of additional elements because it teaches that the additional elements are well known or commercially available. For example the prior arts disclose the following:
Bartkowiak (Genes & Development 24:2303-2316 8/26/2010) teaches that chromatin immunoprecipitation (ChIP) experiments confirm that dCDK12 is present on the transcribed regions of active Drosophila genes (abstract).
Redon (Methods in Molecular Biology, vol 682 2011 pages 249-270) teaches an immunocyto-chemistry method for detecting g-H2AX protein localization. Specimens are incubated with a primary antibody (mouse monoclonal anti-g H2AX for human cells or rabbit polyclonal anti-g-H2AX for mouse cells). Then specimens are incubated with a secondary antibody that is one of the following, depending on the primary antibody: Alexa Fluor 488-conjugated goat anti-mouse IgG or Alexa Fluor 488-conjugated goat anti rabbit IgG. 10. Finally microscopy is performed (pages 252, 255, 257, and Fig 1).
Hegazy (Current Protocols in Cell Biology, 2000 89, e115) discloses a proximity ligation assay for detecting protein-protein interactions and protein modification in cells and tissues in situ. Hegazy teaches a method comprising (1) Two antibodies of different species are selected that recognize two proteins of interest. (2) Secondary antibodies that recognize the Fc regions of the primary antibody species are conjugated with oligonucleotide probes and then incubated with the sample. (3) Ligase and free oligonucleotides that hybridize with the probes bring the oligonucleotides together in a closed circle conformation if the proteins are in close enough proximity. (4) Finally, polymerase is added to the reaction to allow rolling-circle amplification, while fluorescently labeled oligonucleotides hybridize with the rolling-circle product, resulting in the accumulation of fluorescent spots in areas of successful amplification (see page 3 and Fig 1).
Los (Methods in Molecular Biology, 2007 vol. 356 pages 195-208) discloses HaloTag™ technology. The technology allows HaloTag™ fusion proteins within cells to be labeled with a range of standard fluorophores for image analysis (page 205).
Further it is noted that the courts have recognized the following laboratory techniques as well-understood, routine, conventional activity in the life science arts when they are claimed in a merely generic manner (e.g., at a high level of generality) or as insignificant extra-solution activity.
Determining the level of a biomarker in blood by any means, Mayo, 566 U.S. at 79, 101 USPQ2d at 1968; Cleveland Clinic Foundation v. True Health Diagnostics, LLC, 859 F.3d 1352, 1362, 123 USPQ2d 1081, 1088 (Fed. Cir. 2017);
Using polymerase chain reaction to amplify and detect DNA, Genetic Techs. v. Merial LLC, 818 F.3d 1369, 1376, 118 USPQ2d 1541, 1546 (Fed. Cir. 2016); Ariosa Diagnostics, Inc. v. Sequenom, Inc., 788 F.3d 1371, 1377, 115 USPQ2d 1152, 1157 (Fed. Cir. 2015);
Detecting DNA or enzymes in a sample, Sequenom, 788 F.3d at 1377-78, 115 USPQ2d at 1157); Cleveland Clinic Foundation 859 F.3d at 1362, 123 USPQ2d at 1088 (Fed. Cir. 2017);
Immunizing a patient against a disease, Classen Immunotherapies, Inc. v. Biogen IDEC, 659 F.3d 1057, 1063, 100 USPQ2d 1492, 1497 (Fed. Cir. 2011);
Analyzing DNA to provide sequence information or detect allelic variants, Genetic Techs., 818 F.3d at 1377; 118 USPQ2d at 1546;
Freezing and thawing cells, Rapid Litig. Mgmt. 827 F.3d at 1051, 119 USPQ2d at 1375;
Amplifying and sequencing nucleic acid sequences, University of Utah Research Foundation v. Ambry Genetics, 774 F.3d 755, 764, 113 USPQ2d 1241, 1247 (Fed. Cir. 2014)
For the reasons set forth above the claims are not directed to patent eligible subject matter.
9. 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 extension fee 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 date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to AMANDA HANEY whose telephone number is (571)272-8668. The examiner can normally be reached Monday-Friday, 8:15am-4:45pm EST.
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/AMANDA HANEY/Primary Examiner, Art Unit 1682
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