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 .
Status of Claims
Claims 1-12 and 17-20 are pending and are under examination.
Claims 13-16 are withdrawn.
Applicant’s election without traverse of Group I, which includes Claims 1-12 and 17-20 in the reply filed on 04/28/2026 is acknowledged.
Claims 13-16 withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected method for identifying a polypeptide using restriction site- mediate cleavage, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 04/28/2026.
Claim Rejections - 35 USC § 112(b)
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.
Claim 1-12 rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 1, the limitation “the NTAA” lacks proper antecedent basis. Hence, the metes and bounds of the claim are unascertainable.
Claims 2-12 depend from claim 1 and is therefore similarly rejected.
Claim Objections
Claim 1 objected to because of the following informalities: “NTAA” acronyms or abbreviated terms should be spelled out fully upon their first appearance in the claims and can then later be shortened. Appropriate correction is required.
Claim Rejections - 35 USC §102
Claim(s) 1-4, 6-12, and 17-20 is/are rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by Chee et al. (US20190145982A1, published May 2019).
Regarding claim 1, Chee discloses (a) providing the polypeptide and an associated recording tag joined to a solid support; [¶0358]
(b) contacting the polypeptide with a plurality of coding tags, wherein each coding tag of the plurality of coding tags is configured to react selectively with a specific type of amino acid residue(s) and comprises a barcode region with identifying information regarding the specific type of amino acid residue(s) to which the coding tag reacts selectively, thereby obtaining the polypeptide comprising coding tags attached to the specific amino acid residues; (e.g. contacting the peptide with binding agent, wherein the binding agent comprises a first coding tag with identifying information regarding the first binding agent [¶0358]; binding agent can selectively binding to one of the 20 possible natural amino acid residues [¶0312].)
(c) contacting the polypeptide comprising coding tags attached to the specific amino acid residues with a plurality of complementary coding tags, wherein each complementary coding tag of the plurality of complementary coding tags comprises (i) a region complementary to the barcode region of a corresponding coding tag, (ii) a first spacer region complementary to a first complementary spacer region of the recording tag, and (iii) a moiety configured, when in a close proximity, to be covalently coupled to the NTAA of the polypeptide, or to a modified NTAA of the polypeptide; (d) providing conditions for covalently coupling the moiety to the NTAA of the polypeptide or the modified NTAA of the polypeptide; (e) removing complementary coding tags that are not covalently coupled to the NT AA of the polypeptide; (e.g. contacting the peptide with binding agent, wherein the binding agent comprises a first coding tag with identifying information regarding the first binding agent [¶0358]; coding tag further comprises spacer sequences; wherein coding tag’s spacer sequence hybridizes to the complementary spacer sequence on the recording tag [¶0323]. In certain embodiments, an NTAA and its cognate NTAA-specific binding agent are covalently linked, which allows for more stringent washing to be used to remove binding agents that are non-specifically bound, thus increasing the specificity of the assay. [¶0461]. )
(f) transferring identifying information of the barcode region or the region complementary to the barcode region from complementary coding tag covalently coupled to the NTAA of the polypeptide to the recording tag, wherein transferring the identifying information comprises a primer extension or ligation; (e.g. transferring the information of the first coding tag to the recording tag to generate a first order extended recording tag using primer extension [¶0358 and ¶0329])
g) removing the NTAA of the polypeptide, thereby exposing a new NTAA (e.g. “removing the modified NTAA to expose a new NTAA” [[¶0358])
(h) adding a second order complementary spacer region to the recording tag extended at step (f) (e.g . transferring the information of the first coding tag to the recording tag to generate a first order extended recording tag using primer extension [¶0358 and ¶0329], wherein coding tag comprises spacer sequences [¶0320])
(j) repeating steps (c)-(h) one or more times by replacing at step (c) the first spacer region of the complementary coding tags with a second or higher order spacer region complementary to the second or higher order complementary spacer region of the recording tag, and by replacing at step (h) the second complementary spacer region with a third or higher order complementary spacer region; (e.g. steps of contacting the peptide with binding agent, transferring identifying information and spacer, removing NTAA of the peptide are performed in sequential order in separate binding cycle reactions [¶0359])
(k) analyzing the recording tag extended at step (j) by a nucleic acid sequencing method, and obtaining information regarding the specific amino acid residues of the polypeptide, thereby identifying the polypeptide. (e.g. analyzing the recording tag barcodes allows identifying the original peptide being sequenced. [¶0358 and ¶0343]).
Regarding claim 2, Chee further discloses at step (f) transferring information is performed by the primer extension using a DNA polymerase having a strand-displacement ability. (e.g. in some embodiments, use of a non-strand displacing polymerase during primer extension is preferred [¶0288]).
Regarding claim 3, Chee further discloses at step (f) transferring information is performed by a splint ligation. (e.g. spacer sequence in a recording tag initiates a primer extension, or provide a “splint” for a ligation reaction, or mediate a “sticky end” ligation reaction. [¶0323])
Regarding claims 4 and 20, Chee further discloses the NTAA of the polypeptide is removed by an engineered enzyme. (e.g. NTAA is cleaved from the peptide by an engineered acylpeptide hydrolase (APH) [¶0297]).
Regarding claims 7 and 17, Chee further discloses the moiety comprises a click chemistry reactive group. (e.g. Once binding agent binds to a proximal target protein, the reactive coupling moiety on the recording tag (e.g., azide) covalently attaches to the cognate click chemistry coupling moiety on the proximal protein.[¶0283])
Regarding claim 8, Chee further discloses identifying 100 or more different polypeptides simultaneously. (e.g. method allows analyzing a plurality of macromolecules in parallel; where in plurality of macromolecules includes 100 or more macromolecules [¶0369 and ¶0598])
Regarding claim 9, Chee further discloses step (k) comprises bioinformatically matching the obtained information regarding the specific amino acid residues of the polypeptide with corresponding information extracted from a genomic database or a proteomic database. (e.g. Results from sequencing of the extended reporter tag can be associated to their corresponding macromolecules (e.g., peptides, proteins, protein complex) and aligned to the totality of the macromolecule type in the cell (e.g., proteome for peptide, polypeptide, protein macromolecules). [¶0596])
Regarding claim 10, Chee further discloses at step (a) the polypeptide is covalently attached to the associated recording tag. (e.g. polypeptides/peptides covalently linked to their recording tags using click chemistry [¶0428])
Regarding claim 11, Chee further discloses the specific type of amino acid residues is selected from the group consisting of: lysine, arginine, aspartate, glutamate, histidine, cysteine, serine, methionine, tryptophan and tyrosine. (e.g. the binding agent has high affinity to Tyrosine [¶0315]).
Regarding claim 12, Chee further discloses before contacting the polypeptide with the plurality of coding tags, the polypeptide is at least partially denatured to expose the specific amino acid residues to the plurality of coding tags. (e.g. method is used to analyze denatured proteins, polypeptides, and peptides [¶0529])
Regarding claim 17, Chee a kit for identifying a polypeptide immobilized on a solid support, comprising: (a) a plurality of coding tags, wherein each coding tag of the plurality of coding tags is configured to react selectively with a specific type of amino acid residue(s) from the polypeptide and comprises a barcode region with identifying information regarding the specific type of amino acid residue(s) to which the coding tag reacts selectively; (e.g. binding agent comprises a first coding tag with identifying information regarding the first binding agent [¶0358]; binding agent can selectively binding to one of the 20 possible natural amino acid residues [¶0312].)
(b) a plurality of complementary coding tags, wherein each complementary coding tag of the plurality of complementary coding tags comprises (i) a region complementary to the barcode region of a corresponding coding tag, (ii) a first spacer region complementary to a first complementary spacer region of a recording tag associated with the polypeptide, and (iii) a moiety configured, when in a close proximity, to be covalently coupled to the NTAA of the polypeptide, or to a modified NTAA of the polypeptide. (e.g. the binding agent comprises a first coding tag with identifying information regarding the first binding agent [¶0358]; coding tag further comprises spacer sequences; wherein coding tag’s spacer sequence hybridizes to the complementary spacer sequence on the recording tag [¶0323]. In certain embodiments, an NTAA and its cognate NTAA-specific binding agent are covalently linked, which allows for more stringent washing to be used to remove binding agents that are non-specifically bound, thus increasing the specificity of the assay. [¶0461].)
Regarding claim 19, Chee further discloses the recording tag is configured to be joined to the solid support. [¶0013]
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.
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.
Claim(s) 5 and 6 is/are rejected under 35 U.S.C. 103 as being unpatentable over Chee et al. (US20190145982A1, published May 2019) n view of Gunderson (WO2020223133A1, published Nov 2020)
Regarding claim 5, Chee discloses (b) treating the initial NTAA functionalized polypeptide or the secondary NTAA functionalized polypeptide with a suitable medium to eliminate the NTAA, thereby removing the NTAA of the polypeptide. (e.g. eliminate the NTAA can be done using chemical cleavage and enzymatic cleavage including: Edman degradation [¶0567]), reaction with small chemical moieties (e.g. phenylthiocarbamoyl (PTC) , acetyl, or amidinyl (guanidinyl)) [¶0304]). Hence, Chee teaches functionalizing a NTAA of polypeptide with guanidinyl. However, Chee does not disclose functionalizing the N-terminal amino acid (NTAA) of the polypeptide with bis(1H-imidazole-1-yl)methanimine.
Gunderson discloses functionalizing the N-terminal amino acid (NTAA) of the polypeptide with bis(1H-imidazole-1-yl)methanimine [¶0083-0099].
As of the application’ s effective filing date, it would have been prima facie obvious to a person of ordinary skill in the art to select Gunderson’s bis(1H-imidazole-1-yl)methanimine as the guanidinylating reagent in Chee’s method because Chee already identifies amidinyl/guanidinyl NTAA modification as a useful modifier for controlled NTAA cleavage in an Edman-like cyclic peptide sequencing process, while Gunderson teaches the specific reagent and reaction scheme for producing and eliminating the guanidinyl functionalized NTAA. The substitution represents the use of known NTAA functionalized reagent for its known purpose in the same field of peptide sequencing analysis. Because the chemistry, target substrate, and purpose are aligned, a POSA would have been motivated to combine the teachings with a reasonable expectation of success.
Regarding claim 6, Gunderson further discloses treating the initial NTAA functionalized polypeptide or the secondary NTAA functionalized polypeptide with the suitable medium occurs at temperature between about 40°C and about 95°C. (e.g. functionalization of the NTAA reaction occurs at 40°C for 30 minute and elimination reaction happens at 95°C for 30 minute [¶0518])
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.
US 12,123,878 B2
Claim(s) 1 and 8 rejected on the ground of nonstatutory double patenting as being unpatentable over claim(s) 1, 3, 8, 14, 16, and 17 of U.S. Patent No. US12123878B2 (the 878’ patent). Although the claims at issue are not identical, they are not patentably distinct from each other because the rejected claims of the present invention would be anticipated and/or rendered obvious by the subject matter in the claims of the reference patent.
Regarding claim 1, the 878’ patent discloses a method for identifying a polypeptide, the method comprising the steps of:
(a) providing the polypeptide and an associated recording tag joined to a solid support;
(b) contacting the polypeptide with a plurality of coding tags, wherein each coding tag of the plurality of coding tags is configured to react selectively with a specific type of amino acid residue(s) and comprises a barcode region with identifying information regarding the specific type of amino acid residue(s) to which the coding tag reacts selectively, thereby obtaining the polypeptide comprising coding tags attached to the specific amino acid residues;
(c) contacting the polypeptide comprising coding tags attached to the specific amino acid residues with a plurality of complementary coding tags, wherein each complementary coding tag of the plurality of complementary coding tags comprises (i) a region complementary to the barcode region of a corresponding coding tag, (ii) a first spacer region complementary to a first complementary spacer region of the recording tag, and (iii) a moiety configured, when in a close proximity, to be covalently coupled to the NTAA of the polypeptide, or to a modified NTAA of the polypeptide;
(d) providing conditions for covalently coupling the moiety to the NTAA of the polypeptide or the modified NTAA of the polypeptide;
(e) removing complementary coding tags that are not covalently coupled to the NTAA of the polypeptide;
(f) transferring identifying information of the barcode region or the region complementary to the barcode region from complementary coding tag covalently coupled to the NTAA of the polypeptide to the recording tag, wherein transferring the identifying information comprises a primer extension or ligation;
(g) removing the NTAA of the polypeptide, thereby exposing a new NTAA;
(h) adding a second order complementary spacer region to the recording tag extended at step (f);
(j) repeating steps (c)-(h) one or more times by replacing at step (c) the first spacer region of the complementary coding tags with a second or higher order spacer region complementary to the second or higher order complementary spacer region of the recording tag, and by replacing at step (h) the second complementary spacer region with a third or higher order complementary spacer region; and
(k) analyzing the recording tag extended at step (j) by a nucleic acid sequencing method, and obtaining information regarding the specific amino acid residues of the polypeptide, thereby identifying the polypeptide. (e.g. as per claim 1, 3, 16, and 17 of the 878’ patent)
Regarding claim 8, the 878’ patent discloses identifying 100 or more different polypeptides simultaneously. (e.g. as per claim 8 and 14 of the 878’ patent)
19/030,023
Claim(s) 1 and 8 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim(s) 178, 182-186, 189, 194, 196, and 198-205 of U.S. Application No. US 19/030,023 (the 023’ application). Although the claims at issue are not identical, they are not patentably distinct from each other because the rejected claims of the present invention would be anticipated and/or rendered obvious by the subject matter in the claims of the reference patent.
Regarding claim 1, the 023’ application discloses a method for identifying a polypeptide, the method comprising the steps of:
(a) providing the polypeptide and an associated recording tag joined to a solid support;
(b) contacting the polypeptide with a plurality of coding tags, wherein each coding tag of the plurality of coding tags is configured to react selectively with a specific type of amino acid residue(s) and comprises a barcode region with identifying information regarding the specific type of amino acid residue(s) to which the coding tag reacts selectively, thereby obtaining the polypeptide comprising coding tags attached to the specific amino acid residues;
(c) contacting the polypeptide comprising coding tags attached to the specific amino acid residues with a plurality of complementary coding tags, wherein each complementary coding tag of the plurality of complementary coding tags comprises (i) a region complementary to the barcode region of a corresponding coding tag, (ii) a first spacer region complementary to a first complementary spacer region of the recording tag, and (iii) a moiety configured, when in a close proximity, to be covalently coupled to the NTAA of the polypeptide, or to a modified NTAA of the polypeptide;
(d) providing conditions for covalently coupling the moiety to the NTAA of the polypeptide or the modified NTAA of the polypeptide;
(e) removing complementary coding tags that are not covalently coupled to the NTAA of the polypeptide;
(f) transferring identifying information of the barcode region or the region complementary to the barcode region from complementary coding tag covalently coupled to the NTAA of the polypeptide to the recording tag, wherein transferring the identifying information comprises a primer extension or ligation;
(g) removing the NTAA of the polypeptide, thereby exposing a new NTAA;
(h) adding a second order complementary spacer region to the recording tag extended at step (f);
(j) repeating steps (c)-(h) one or more times by replacing at step (c) the first spacer region of the complementary coding tags with a second or higher order spacer region complementary to the second or higher order complementary spacer region of the recording tag, and by replacing at step (h) the second complementary spacer region with a third or higher order complementary spacer region; and
(k) analyzing the recording tag extended at step (j) by a nucleic acid sequencing method, and obtaining information regarding the specific amino acid residues of the polypeptide, thereby identifying the polypeptide. (e.g. as per claim 178, 182-186, 189, 196, and 198-205 of the 023’ application)
Regarding claim 8, the 023’ application discloses identifying 100 or more different polypeptides simultaneously. (e.g. as per claim 194 of the 023’ application)
Conclusion
No claims are allowed
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Khai Quynh Tien Pham whose telephone number is (571)272-6998. The examiner can normally be reached M-T, 9-4 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, Heather Calamita can be reached at (571) 272-2876. 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.
/KHAI QUYNH TIEN PHAM/ Examiner, Art Unit 1684
/JEREMY C FLINDERS/ Primary Examiner, Art Unit 1684
Prosecution Insights