CTNF 18/572,979 CTNF 100710 DETAILED ACTION 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. Status of the Claims Claims 1-15 are pending. Examiner previously required a restriction (dated March 3, 2026). In response, Applicant elected, without traverse, Group I which encompasses claims 1, 2, 4, and 5. Accordingly, claims 3 and 6-15 are withdrawn. Status of Priority The present application is a 35 U.S.C. § 371 national stage patent application of International patent application PCT/KR2023/012759, filed on August 29, 2023. This application also claims the benefits of foreign priority to KR10-2022-0108530, filed on August 29, 2022. Specification - Disclosure 07-29 AIA The disclosure is objected to because of the following informalities: Pg. 4 of the instant specification discloses Chemical Formula 1 to be: PNG media_image1.png 271 931 media_image1.png Greyscale . According to the figure above, it appears that the mass number of N is 16 rather than 15. Please double check to ensure that the mass number of N is 15 (as explained in the instant specification, pg. 4, lines 10-15) and to replace the figures with ones that are clearer and more readable . Appropriate correction is required. 06-31 AIA The specification has not been checked to the extent necessary to determine the presence of all possible minor errors. Applicant’s cooperation is requested in correcting any errors of which applicant may become aware in the specification. Drawings 06-22 AIA The drawings are objected to because the chemical structure and atom labeling within figures 1-3 and the text within figure 4 are not clearly depicted and are difficult to read. Please provide higher-resolution figures with improved clarity. Please also double check the structures of Chemical Formula 1 and ensure that the atoms are labeled with their correct mass numbers (i.e., N has mass number 15 and not 16) . Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance. Claim Objections Claims 2 and 4 are objected to under 37 CFR 1.75 as being a substantial duplicate of claim 1. Regarding claim 2: Claim 1 is directed to heavy biotin-phenol and heavy desthiobiotin-phenol, whereas claim 2 is directed to the same two compounds of claim 1 with the added recitation of the compounds’ intended use as a “probe for proximity molecular labeling.” Claim 2 does not further limit the compounds structurally. As explained in MPEP § 2114, section II: “‘[A]pparatus claims cover what a device is, not what a device does .’ Hewlett-Packard Co. v. Bausch & Lomb Inc., 909 F.2d 1464, 1469, 15 USPQ2d 1525, 1528 (Fed. Cir. 1990) (emphasis in original). A claim containing a ‘recitation with respect to the manner in which a claimed apparatus is intended to be employed does not differentiate the claimed apparatus from a prior art apparatus’ if the prior art apparatus teaches all the structural limitations of the claim.” This can also be translated to a compound claim. A compound claim covers what a compound is, not what a compound does. Therefore, a claim containing a recitation with respect to the manner in which a claimed compound is intended to be employed does not differentiate the claimed compound from a prior art compound (or, in the instant case, another compound claim within the same claim set) if the prior art compound (or other compound claim) teaches all the structural limitations of the claim in question. Therefore, instant claim 2 is not further limiting the subject matter of the claim upon which it depends and is, in fact, a substantial duplicate of instant claim 1. Regarding claim 4: Claim 4 is directed towards a composition for labeling a protein or peptide, comprising the compound of claim 1 with no additional components specified. Therefore, the claim language of instant claim 4 suggests that the composition can be identical to the compound of instant claim 1. Therefore, claim 4 is not further limiting the subject matter of the claim upon which it depends and is, in fact, a substantial duplicate of instant claim 1. When two claims in an application are duplicates or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing one claim to object to the other as being a substantial duplicate of the allowed claim. See MPEP § 608.01(m). Examiner’s note on novelty and nonobviousness Novelty: The Examiner conducted a prior art search and could not find any prior art that explicitly discloses the compounds of instant claim 1. Thus, the instant invention with respect to claims 1, 2, 4, and 5 is considered novel. Nonobviousness: Reference 1: Hung et al. (Hung) (Hung, V. et al. Proteomic Mapping of the Human Mitochondrial Intermembrane Space in Live Cells via Ratiometric APEX Tagging. Molecular Cell 2014 , 55, 332-341. Hung “combine[d] APEX technology with a SILAC-based ratiometric tagging strategy to substantially reduce unwanted background and achieve nanometer spatial resolution. This is applied to map the proteome of the mitochondrial intermembrane space (IMS), which can freely exchange small molecules with the cytosol. [Their] IMS proteome of 127 proteins has >94% specificity and includes nine newly discovered mitochondrial proteins. This approach will enable scientists to map proteomes of cellular regions that were previously inaccessible” (see Hung, abstract). The disclosure of Hung also teaches how to use proximity labeling within the mitochondrial intermembrane space (similar to the instant invention). The main difference between Hung and the instant invention is as follows: In Hung, they explicitly teach that their “technique should always be used with a quantitative proteomic method such as SILAC or iTRAQ (isobaric tag for relative and absolute quantitation)” (pg. 339, left col., 1 st paragraph, 2 nd sentence). Hung does not suggest isotopically labeling biotin-phenol itself and, instead, explicitly suggests using iTRAQ, another chemical labeling method known in the art. In the instant invention, the inventors explicitly teach isotopically label biotin-phenol itself and use the isotopically labeled form of biotin-phenol in proximity labeling. Reference 2: Qin et al. (Qin) (Qin, W. et al. Deciphering molecular interactions by proximity labeling. Nature Methods 2021 , 18, 133-143.) Qin “review[s] the development of PL [proximity labeling] technologies and highlight studies that have applied PL to the discovery and analysis of molecular interactions. In particular, [they] focus on the use of PL for mapping protein–protein, protein–RNA and protein– DNA interactions in living cells and organisms” (abstract). Qin also provides the general peroxidase- and biotin ligase-based proximity labeling methods for protein-protein interaction mapping (see Fig. 1 which is also reproduced below): PNG media_image2.png 837 1174 media_image2.png Greyscale According to the figure, chemical labeling is involved, however, the labeling method suggested is TMT labeling rather than isotopically labeled biotin-phenol itself. In view of Hung and Qin, it is not obvious to make the compounds of claim 1 or formulate the compounds into a composition as the prior art does not suggest to isotopically label biotin-phenol itself and, instead, suggests to use other chemical labeling methods like TMT or iTRAQ. Therefore, the instant invention with respect to claims 1, 2, 4, and 5 is considered nonobvious. Claim Rejections - 35 USC § 112(d) 07-36 AIA The following is a quotation of 35 U.S.C. 112(d): (d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers. The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph: Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers. 07-36-01 AIA Claim s 2 and 4 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph , as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. See reasoning as explained in the “ Claim Objections ” section above . Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements. Allowable subject matter 12-151-08 AIA 07-43 12-51-08 Claim 1 is allowed. Claim 5 is objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims. Conclusion Claim 1 is allowed. Claim 5 is objected to. Claims 2 and 4 are rejected . Any inquiry concerning this communication or earlier communications from the examiner should be directed to KRISTEN ROMERO whose telephone number is (571)272-6478. The examiner can normally be reached M-F 9:30 AM - 6:00 PM ET. 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, JEFFREY H. MURRAY can be reached at (571) 272-9023. 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. /KRISTEN W ROMERO/Examiner, Art Unit 1624 /JEFFREY H MURRAY/Supervisory Patent Examiner, Art Unit 1624 Application/Control Number: 18/572,979 Page 2 Art Unit: 1624 Application/Control Number: 18/572,979 Page 3 Art Unit: 1624 Application/Control Number: 18/572,979 Page 4 Art Unit: 1624 Application/Control Number: 18/572,979 Page 5 Art Unit: 1624 Application/Control Number: 18/572,979 Page 6 Art Unit: 1624 Application/Control Number: 18/572,979 Page 7 Art Unit: 1624 Application/Control Number: 18/572,979 Page 8 Art Unit: 1624
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