Prosecution Insights
Last updated: April 19, 2026
Application No. 17/143,890

Use of Amino Acids to Enhance Signal in Mass Spectral Analyses

Final Rejection §DP
Filed
Jan 07, 2021
Examiner
HUANG, MICKEY NMN
Art Unit
1758
Tech Center
1700 — Chemical & Materials Engineering
Assignee
Regeneron Pharmaceuticals, Inc.
OA Round
4 (Final)
63%
Grant Probability
Moderate
5-6
OA Rounds
3y 4m
To Grant
99%
With Interview

Examiner Intelligence

Grants 63% of resolved cases
63%
Career Allow Rate
58 granted / 92 resolved
-2.0% vs TC avg
Strong +56% interview lift
Without
With
+55.8%
Interview Lift
resolved cases with interview
Typical timeline
3y 4m
Avg Prosecution
38 currently pending
Career history
130
Total Applications
across all art units

Statute-Specific Performance

§101
7.1%
-32.9% vs TC avg
§103
37.4%
-2.6% vs TC avg
§102
21.7%
-18.3% vs TC avg
§112
26.0%
-14.0% vs TC avg
Black line = Tech Center average estimate • Based on career data from 92 resolved cases

Office Action

§DP
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 . Response to Arguments Applicant's arguments filed 01/29/26 have been fully considered but they are not persuasive. Applicant’s ground of traversal is directed to the current claim fails to disclose a limitation similar to that of claim 1 of App. No. 18/203,854, wherein the claim recites “the separation between sample components on the separation column is not increased by addition of the small molecule additive in the mobile phase”. Examiner respectfully disagrees. In its currently drafted form, the limitation “the separation between sample components on the separation column is not increased by addition of the small molecules additive in the mobile phase” is interpreted as an intended result of a process step positively recited (i.e. adding small molecule additive to the mobile phase). In method claims, it is the overall method steps that are given patentable weight not the intended result thereof because the intended result does not materially alter the overall method. In method claims, the intended result is not given patentable weight when it simply expresses the intended result of a process step positively recited (MPEP § 2111.04). As such, when considering the limitation regarding the separation between samples components on the column is not increased as an intended result, the subject matter of claim 1 of the current application is not patentably distinct from claim 5 of the ‘854. As such the non-statutory double patenting rejection is maintained. 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. Claim(s) 1, 4, 10, 16-17, 21, 25, 30, and 32 is/are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim(s) 5, 6, 6, 16-17, 20, 24, 30, and 32 of copending Application No. 18/203,854 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because: Regarding claim 1, claim 5 of the reference application discloses all the limitation of pending application. Claim 5 of the reference application disclose “first or second small molecule additive” instead of an embodiment of using 1mM-2mM of first and second small molecule additive. It would have been obvious to one of ordinary skill in the art to select an embodiment of using 1mM-2MM for both first and second small molecule additive (“first or second” includes an embodiment of “first and second”). Regarding claim 4, claim 6 of the reference application discloses the small molecule additive is a glycine. Regarding claim 10, claim 6 of the reference application discloses the small molecule additive in the second mobile phase is also glycine (i.e. “first or second” small molecule additive). Regarding claim 16-17, claims 16-17 of the reference application disclose identical limitation. Regarding claim 21 (incorporating parent claim 20), claims 20 of the reference application discloses the identical limitation. Regarding claim 25, claim 24 of the reference application discloses the identical limitation. Regarding claim 30, claim 30 of the reference application discloses the identical limitation. Regarding claim 32, claim 32 of the reference application discloses the identical limitation. Allowable Subject Matter The following is a statement of reasons for the indication of allowable subject matter: Claims 1, 4, 10, 16-17, 21, 25, 30, and 32 would be allowable if rewritten or amended to overcome the rejection(s) set forth in this Office action. Claims 14, 18, 20, 23, and 27-29 are 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. The closest prior art, Shou et al. (“Simple means to alleviate sensitivity loss by trifluoroacetic acid (TFA) mobile phases in the hydrophilic interaction chromatography-electrospray tandem mass spectrometric (HILIC-ESI/MS/MS) bioanalysis of basic compounds”, 2005; hereinafter Shou) as cited in IDS, discloses a mean to alleviate sensitivity loss (reads on instantly claimed method of enhancing a mass spectral signal) in mass spectrometry, comprising: subjecting a prepared sample of human plasma in a liquid chromatography column to perform separation at ambient temperature so the components of interest enter the stationary phase (interpreted as contacting a sample to a separation column under conditions that permit sample components to bind the substrate) (2.2 Sample Preparation- 2.3. LC-MS/MS method); applying an aqueous mobile phase (reads on instantly claimed first mobile phase gradient) comprising of TFA in water (interpreted as a small molecule additive) in a Betasil silica column (3. Results and discussion, Pg. 189, Column 2 – Page 191, Column 1); applying acetonitrile directly to the aqueous mobile phase (referred to as organic mobile phase in prior art) (interpreted as second mobile phase gradient) in the Betasil silica column (3. Results and discussion, Pg. 189, Column 2-Page 191, Column 1); conducting mass spectrometric analysis on eluted sample components (2.2 Sample preparation-2.3. LC-MS/MS method). However, Shou does not disclose small molecule additive selected from a group of amino acids comprising glycine, alanine, or serine. The second closest art, Goklen et al. (US 7,241,866 B2; hereinafter Goklen) discloses that amine or amino acids selected from L-proline, D-proline, trans-4-hydroxy-L-proline, trans-4-hydroxy-D-proline, glycine, L-threonine, D-threonine, L-lysine, D-lysince, L-methionine, D-valine, L-valine and esters of the aforementioned L- and D-amino acids help improve the resolution or productivity of peptide and lipopetitide purification in a liquid chromatography (Abstract and claim 3). However, Goklen discloses that improvements work with solvent comprising of water, methanol, and ethyl acetate and does not disclose TFA, formic acid, acetic acid, nor acetonitrile. Furthermore, Goklen does not suggest nor anticipate that the disclosure will work in a LC-MS system. Shou is directed to minimizing the suppression of ESI signals of analytes in LC-MS due to TFA forming gas-phase ion pairs with positively charged analyte ions; the problem Goklen is attempting to solve is the co-elution of a peptide or lipopeptide compound with its impurities at the same time or nearly the same time from a LC column, where the peptide or lipopeptide compound and its impurities are analyzed using UV detection rather than mass spectrometry. Furthermore, since Shou teaches that the MS signal detection can be improved (i.e. with the addition of either acetic or propionic acid) without increased LC separation (i.e. with keeping the same elution order and retention times of the eight basic compounds), it does not appear that one of ordinary skill in the art would be motivated or enabled to use 1 mM-2mM of the claimed proteins to resolve the problem in Shou. Conclusion THIS ACTION IS MADE FINAL. 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. Any inquiry concerning this communication or earlier communications from the examiner should be directed to MICKEY HUANG whose telephone number is (571)272-7690. The examiner can normally be reached M-F 9:30-5:30 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, Maris Kessel can be reached at 5712707698. 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. /M.H./ Examiner, Art Unit 1758 /LYLE ALEXANDER/ Supervisory Patent Examiner, Art Unit 1797
Read full office action

Prosecution Timeline

Jan 07, 2021
Application Filed
Feb 09, 2023
Examiner Interview (Telephonic)
Feb 09, 2023
Examiner Interview Summary
Feb 21, 2023
Examiner Interview (Telephonic)
Mar 07, 2023
Response after Non-Final Action
Aug 13, 2023
Non-Final Rejection — §DP
Nov 21, 2023
Response Filed
Jan 23, 2024
Final Rejection — §DP
Apr 11, 2024
Interview Requested
Apr 18, 2024
Applicant Interview (Telephonic)
Apr 25, 2024
Examiner Interview Summary
May 22, 2024
Notice of Allowance
Aug 21, 2024
Response after Non-Final Action
Sep 02, 2024
Response after Non-Final Action
Oct 17, 2024
Response after Non-Final Action
Dec 19, 2024
Response after Non-Final Action
Dec 19, 2024
Response after Non-Final Action
Dec 21, 2024
Response after Non-Final Action
Dec 23, 2024
Response after Non-Final Action
Dec 26, 2024
Response after Non-Final Action
Jul 30, 2025
Response after Non-Final Action
Jul 31, 2025
Response after Non-Final Action
Aug 06, 2025
Response after Non-Final Action
Sep 26, 2025
Request for Continued Examination
Sep 29, 2025
Response after Non-Final Action
Oct 24, 2025
Non-Final Rejection — §DP
Jan 29, 2026
Response Filed
Feb 26, 2026
Final Rejection — §DP (current)

Precedent Cases

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Study what changed to get past this examiner. Based on 5 most recent grants.

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Prosecution Projections

5-6
Expected OA Rounds
63%
Grant Probability
99%
With Interview (+55.8%)
3y 4m
Median Time to Grant
High
PTA Risk
Based on 92 resolved cases by this examiner. Grant probability derived from career allow rate.

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