Prosecution Insights
Last updated: April 19, 2026
Application No. 18/296,895

Protein Tyrosine Phosphatase 1B Inhibited Neutrophils, Neutrophil-Dendritic Cell Hybrids and Uses Thereof

Non-Final OA §103§DP
Filed
Apr 06, 2023
Examiner
SHIBUYA, MARK LANCE
Art Unit
1631
Tech Center
1600 — Biotechnology & Organic Chemistry
Assignee
Wisconsin Alumni Research Foundation
OA Round
1 (Non-Final)
32%
Grant Probability
At Risk
1-2
OA Rounds
3y 9m
To Grant
57%
With Interview

Examiner Intelligence

Grants only 32% of cases
32%
Career Allow Rate
51 granted / 158 resolved
-27.7% vs TC avg
Strong +25% interview lift
Without
With
+24.9%
Interview Lift
resolved cases with interview
Typical timeline
3y 9m
Avg Prosecution
28 currently pending
Career history
186
Total Applications
across all art units

Statute-Specific Performance

§101
2.9%
-37.1% vs TC avg
§103
38.2%
-1.8% vs TC avg
§102
18.1%
-21.9% vs TC avg
§112
27.0%
-13.0% vs TC avg
Black line = Tech Center average estimate • Based on career data from 158 resolved cases

Office Action

§103 §DP
DETAILED ACTION Notice of Pre-AIA or AIA Status The present application, 18296895, US 20230323301, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA . Claims 1-24 are pending. Claims 12-19 and 21-24 are withdrawn. Claims 1-11 and 20 are examined. Priority The filing receipt, mailed 6/1/23, states that this application, 18296895, filed 4/6/2023, claims benefit of 63/327,888, filed 04/06/2022 and claims benefit of 63/429,886, filed 12/02/2022. Information Disclosure Statement The information disclosure statement (IDS) submitted on 5/8/2024 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner. 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. The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows: 1. Determining the scope and contents of the prior art. 2. Ascertaining the differences between the prior art and the claims at issue. 3. Resolving the level of ordinary skill in the pertinent art. 4. Considering objective evidence present in the application indicating obviousness or nonobviousness. 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. 1. Claim(s) 1-11 and 20 is/are rejected under 35 U.S.C. 103 as being unpatentable over Slukvin, US 20200385676, Klemm, 2021, “Investigating mechanisms of directed neutrophil migration in vitro,” PhD. Dissertation, (Molecular and Cellular Pharmacology), University of Wisconsin-Madison, Morishima, 2014, Haematologica, vol 99, pages 19 to 27,and Massena, 2015, BLOOD, vol 126, pages 2016 to 2026. Slukvin, US 20200385676, teaches throughout the publication and abstract, and at para [0004], [0012] method of producing modified, mature neutrophils from pluripotent stem cells, the method comprising: transiently introducing exogenous ETV2 mRNA in human pluripotent cells. Slukvin, US 20200385676, teaches, at para [0014], culturing the ETV2- pluripotent stem cells in serum-free culture medium fibroblast growth factor 2 (FGF2), to produce a population of ETV2-hemogenic endothelial cells (ETV2-HECs); culturing the ETV2-HECs in serum-free and xeno-free culture medium (b) comprising granulocyte-macrophage colony-stimulating factor (GM-CSF) and FGF2 for a sufficient time to produce myeloid progenitors; culturing the myeloid progenitors in serum-free and xeno-free culture medium (c) comprising granulocyte - colony stimulating factor (G-CSF) and retinoic acid receptor agonist for a time sufficient to differentiate the myeloid progenitors into a population of modified mature neutrophils; and at para [0012]-[0013], teaches and fairly suggests (d) selecting mature neutrophils from the population of modified mature neutrophils. Slukvin, US 20200385676, e.g., at reference [0012], [0130], teaches UM171, as in instant claim 2; Am580, as in instant claim 6; at para [0077], teaches CD16 and CD15, as in instant claim 9. Slukvin, US 20200385676, does not teach stem cells having (a) inhibited expression of protein tyrosine phosphatase 1B (PTP1b). Slukvin, does not teach media comprising vascular endothelial growth factor-165 (VEGF-165). Klemm, throughout the publication and abstract, at pp. 7-10, teaches PTP1B, as in instant claim 3; at pp. 64-65, teaches CRISPR/Cas9-mediated knockout of PTP1B in human bone marrow-derived iPSC cells (Figure 3-5), as in instant claims 3-5. Klemm, at p. 78, teaches CRISPR/Cas9-mediated knockout of PTP1B increases motility in iPSC-derived neutrophils (Figure 3-6). Morishima, at p. 20, left column, para 5, teaches neutrophil differentiation of induced pluripotent stem (iPS) cells treated with vascular endothelial growth factor (VEGF) 165 (40 ng/ml, on Day 4, and replaced on day 6. Massena, throughout the publication and abstract, teaches Vascular endothelial growth factor A (VEGF-A) recruits neutrophils. Massena, at p. 2017, left column, last paragraph, at pp. 2017-2018, bridging paragraph, teaches recombinant murine VEGF-A165, which, is taken to read on both VEGF-165, as in the instant claims, and VEGF-A, as in Massena. Massena teaches It would have been prima facie obvious before the filing date of the instant application for one of ordinary skill in the art to have combined stem cells having (a) inhibited expression of protein tyrosine phosphatase 1B (PTP1b) and media comprising vascular endothelial growth factor-165 (VEGF-165), as taught by Klemm and Morishima, respectively in methods of producing modified, mature neutrophils from pluripotent stems cells, as described by Slukvin. One of ordinary skill in the art would have motivated to have combined stem cells having (a) inhibited expression of protein tyrosine phosphatase 1B (PTP1b) in the method of Slukvin, US 20200385676, in order increase motility in iPSC-derived neutrophils, as taught by Klemm. One of ordinary skill in the art would have motivated to use media comprising vascular endothelial growth factor-165 (VEGF-165), as exemplified by Morishima, because Vascular endothelial growth factor A (VEGF-A) recruits neutrophils, as taught by Massena. 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. 1. Claims 1-11 and 20 are rejected on the ground of nonstatutory double patenting as being unpatentable over reference claims 1-3, 6 of Slukvin, U.S. Patent No. 12,410,401, in view of Slukvin, US 20200385676, Klemm, 2021, “Investigating mechanisms of directed neutrophil migration in vitro,” PhD. Dissertation, (Molecular and Cellular Pharmacology), University of Wisconsin-Madison, Morishima, 2014, Haematologica, vol 99, pages 19 to 27,and Massena, 2015, BLOOD, vol 126, pages 2016 to 2026. Slukvin, U.S. Patent No. 12,410,401, (US ‘401, Patent), in reference claims 1-6, claims methods of producing in vitro derived CD 16+ CD neutrophils from pluripotent stem cells, the method comprising: introducing exogenous ETV2 mRNA in human pluripotent cells. Slukvin, (US ‘401, Patent), does not claim method comprising mature neutrophil cells having (a) inhibited expression of protein tyrosine phosphatase 1B (PTP1b), ETV2-HEC, GM-CSF, FGF2. Slukvin, does not teach media comprising vascular endothelial growth factor-165 (VEGF-165). Slukvin, does not teach stem cells having (a) inhibited expression of protein tyrosine phosphatase 1B (PTP1b). Slukvin, does not teach media comprising vascular endothelial growth factor-165 (VEGF-165). Slukvin, US 20200385676, teaches, at para [0014], culturing the ETV2- pluripotent stem cells in serum-free culture medium fibroblast growth factor 2 (FGF2), to produce a population of ETV2-hemogenic endothelial cells (ETV2-HECs); culturing the ETV2-HECs in serum-free and xeno-free culture medium (b) comprising granulocyte-macrophage colony-stimulating factor (GM-CSF) and FGF2 for a sufficient time to produce myeloid progenitors; culturing the myeloid progenitors in serum-free and xeno-free culture medium (c) comprising granulocyte - colony stimulating factor (G-CSF) and retinoic acid receptor agonist for a time sufficient to differentiate the myeloid progenitors into a population of modified mature neutrophils; and at para [0012]-[0013], teaches and fairly suggests (d) selecting mature neutrophils from the population of modified mature neutrophils. Slukvin, , US 20200385676 e.g., at reference [0012], [0130], teaches UM171, as in instant claim 2; Am580, as in instant claim 6; at para [0077], teaches CD16 and CD15, as in instant claim 9. Klemm, throughout the publication and abstract, at pp. 7-10, teaches PTP1B, as in instant claim 3; at pp. 64-65, teaches CRISPR/Cas9-mediated knockout of PTP1B in human bone marrow-derived iPSC cells (Figure 3-5), as in instant claims 3-5. Klemm, at p. 78, teaches CRISPR/Cas9-mediated knockout of PTP1B increases motility in iPSC-derived neutrophils (Figure 3-6). Morishima, at p. 20, left column, para 5, teaches neutrophil differentiation of induced pluripotent stem (iPS) cells treated with vascular endothelial growth factor (VEGF) 165 (40 ng/ml, on Day 4, and replaced on day 6. Massena, throughout the publication and abstract, teaches Vascular endothelial growth factor A (VEGF-A) recruits neutrophils. Massena, at p. 2017, left column, last paragraph, at pp. 2017-2018, bridging paragraph, teaches recombinant murine VEGF-A165, which, is taken to read on both VEGF-165, as in the instant claims, and VEGF-A, as in Massena. Massena teaches It would have been prima facie obvious before the filing date of the instant application for one of ordinary skill in the art to have combined stem cells having (a) inhibited expression of protein tyrosine phosphatase 1B (PTP1b) and media comprising vascular endothelial growth factor-165 (VEGF-165), as taught by Klemm and Morishima, respectively in methods of producing modified, mature neutrophils from pluripotent stems cells, as claimed by Slukvin, (US ‘401, Patent). One of ordinary skill in the art would have motivated to have combined stem cells having (a) inhibited expression of protein tyrosine phosphatase 1B (PTP1b) in the method of Slukvin, US 20200385676, in order increase motility in iPSC-derived neutrophils, as taught by Klemm. One of ordinary skill in the art would have motivated to use media comprising vascular endothelial growth factor-165 (VEGF-165), as exemplified by Morishima, because Vascular endothelial growth factor A (VEGF-A) recruits neutrophils, as taught by Massena. Conclusion 1. Claims 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. Claims 1-11 and 20 are rejected. 2. Any inquiry concerning this communication or earlier communications from the examiner should be directed to Mark L Shibuya whose telephone number is (571)272-0806. The examiner can normally be reached M-F, 9AM-4:30PM. 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, James (Doug) Schultz, can be reached at (571) 272-0763. 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. MARK L. SHIBUYA Primary Patent Examiner Art Unit 1631 /MARK L SHIBUYA/Primary Patent Examiner, Art Unit 1631
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Prosecution Timeline

Apr 06, 2023
Application Filed
Feb 05, 2026
Non-Final Rejection — §103, §DP (current)

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

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Prosecution Projections

1-2
Expected OA Rounds
32%
Grant Probability
57%
With Interview (+24.9%)
3y 9m
Median Time to Grant
Low
PTA Risk
Based on 158 resolved cases by this examiner. Grant probability derived from career allow rate.

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