Prosecution Insights
Last updated: April 19, 2026
Application No. 18/170,671

PHARMACEUTICAL COMPOSITION COMPRISING MODIFIED NATURAL KILLER CELLS AND ANTIGEN-SPECIFIC T CELLS, MANUFACTURING METHOD THEREOF, AND METHOD OF USING THE SAME

Non-Final OA §102§112§DP
Filed
Feb 17, 2023
Examiner
GRABER, JAMES J
Art Unit
1631
Tech Center
1600 — Biotechnology & Organic Chemistry
Assignee
National Yang Ming Chiao Tung University
OA Round
1 (Non-Final)
46%
Grant Probability
Moderate
1-2
OA Rounds
3y 9m
To Grant
99%
With Interview

Examiner Intelligence

Grants 46% of resolved cases
46%
Career Allow Rate
84 granted / 181 resolved
-13.6% vs TC avg
Strong +57% interview lift
Without
With
+57.3%
Interview Lift
resolved cases with interview
Typical timeline
3y 9m
Avg Prosecution
40 currently pending
Career history
221
Total Applications
across all art units

Statute-Specific Performance

§101
5.1%
-34.9% vs TC avg
§103
32.3%
-7.7% vs TC avg
§102
15.4%
-24.6% vs TC avg
§112
28.9%
-11.1% vs TC avg
Black line = Tech Center average estimate • Based on career data from 181 resolved cases

Office Action

§102 §112 §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 . Detailed Action This action is in response to the papers filed January 14, 2026. Election/Restrictions Applicant’s reply filed 01/14/2026 to the Requirement for Restriction/Election mailed 11/17/2025 is acknowledged. Applicant elected without traverse Invention 1, claims 1-6, drawn to a method of manufacturing a pharmaceutical composition. Claim 7-13 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.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 01/14/2026. On page 5 of the Requirement for Restriction/Election mailed 11/17/2025, the examiner required election of a specific species of cancer. Applicant’s reply filed 01/14/2026 is nonresponsive to the species election requirement. However, since the cancer type is not particularly pertinent to elected Invention I (method of making), as claimed, the examiner is withdrawing the species election requirement in an effort to expediate prosecution. Claim Listing The instant claims are the original claims filed on 02/17/2023. Claims 1-13 are pending. Claims 7-13 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention. Claims 1-6 are under examination. Effective Filing Date The instant application 18/170,671 was filed on 02/17/2023. No earlier priority claims have been made. Therefore, the effective filing date of the claims is 02/17/2023. Information Disclosure Statement The information disclosure statement (IDS) submitted on 03/26/2025 has been considered. The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, or by applicant in an information disclosure statement (IDS), they have not been considered. Claim Objections Claim 1 is objected to because of the following informalities: The phrase “a negative selection of CD3-CD19-CD14- is not performed” in claim 1 should be “a negative selection of CD3-CD19-CD14- cells is not performed” instead. Appropriate action is required. Claim Rejections - 35 USC § 112 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 1-6 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. Claim 1 recites the negative limitation of “wherein a negative selection of CD3-CD19-CD14- is not performed on the mononuclear cells prior to the contact step.” However, the claim previously recites two distinct “contacting” steps: (1) a first contact step of “contacting the mononuclear cells with a first culturing medium comprising IL-15, IL-12 and IL-18 for about 1-6 day(s) to obtain a cultured cell population” and (2) a second contact step of “contacting the cultured cell population with a second culturing medium comprising IL-15 and IL-12 for about 1-6 day(s) after contacting with the first culturing medium.” Therefore, the limitation “the contact step” in the negative limitation lacks sufficient antecedent basis because it is unclear whether the limitation refers to (1) the first contact step or (2) the second contact step. For these reasons, one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. Dependent claims 2-6 are included in the basis of the rejection because they do not correct the deficiencies of the claim upon which they depend. Claim 4 is 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 4 contains the trademark/trade name AIM-V™ (U.S. Registration No. 1,481,343; Serial No. 73,659,594). Where a trademark or trade name is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph. See Ex parte Simpson, 218 USPQ 1020 (Bd. App. 1982). The claim scope is uncertain since the trademark or trade name cannot be used properly to identify any particular material or product. A trademark or trade name is used to identify a source of goods, and not the goods themselves. Thus, a trademark or trade name does not identify or describe the goods associated with the trademark or trade name. In the present case, the trademark/trade name is used to identify/describe a hematopoietic cell culture medium, and, accordingly, the identification/description is indefinite. For these reasons, one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. Claim 6 is 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 6 recites “the serum protein comprises a human platelet lysate.” The recitation is indefinite because “human platelet lysate” is not a “serum protein,” as claimed. Serum proteins are proteins found in blood serum; whereas, human platelet lysate is a composition produced by inducing lysis of human platelets, thereby releasing growth factors and other cellular components from the platelets. Therefore, claim that the “serum protein comprises a human platelet lysate,” as in claim 6, lacks technical sense because human platelet lysate is not a species of serum proteins. For these reasons, one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. Claim Rejections - 35 USC § 102 The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action: A person shall be entitled to a patent unless – (a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention. Claims 1-6 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by US 2021/0260115 A1 to Lee et al. Lee discloses a method, comprising: obtaining mononuclear cells from a subject; contacting the mononuclear cells with a first culturing medium comprising IL-15, IL-12 and IL-18 for about 1-6 day(s) to obtain a cultured cell population; and contacting the cultured cell population with a second culturing medium comprising IL-15 and IL-12 for about 1-6 day(s) after contacting with the first culturing medium. See, e.g., Abstract; Figure 7; paragraphs 14-15, 20-21, 24; claims 8, 14, 15, and 20. Claim 1 further recites that the method is performed to manufacture a pharmaceutical composition for treating cancer, and the mononuclear cells are obtained from a subject with cancer. Lee discloses the disclosed process is performed to manufacture a pharmaceutical composition for treating cancer (par. 4-5, 8, 49, 62), and the mononuclear cells are obtained from a subject with cancer (par. 10, 44, 59; claim 5). Claim 1 further recites that a negative selection of CD3-CD19-CD14- is not performed on the mononuclear cells prior to the contact step. This limitation is anticipated by Lee for at least the following reasons: MPEP 2173.05(i) instructs: Any negative limitation or exclusionary proviso must have basis in the original disclosure. If alternative elements are positively recited in the specification, they may be explicitly excluded in the claims. See In re Johnson, 558 F.2d 1008, 1019, 194 USPQ 187, 196 (CCPA 1977) ("[the] specification, having described the whole, necessarily described the part remaining."). See also Ex parte Grasselli, 231 USPQ 393 (Bd. App. 1983), aff’d mem., 738 F.2d 453 (Fed. Cir. 1984). In describing alternative features, the applicant need not articulate advantages or disadvantages of each feature in order to later exclude the alternative features. See Inphi Corporation v. Netlist, Inc., 805 F.3d 1350, 1356-57, 116 USPQ2d 2006, 2010-11 (Fed. Cir. 2015). The mere absence of a positive recitation is not basis for an exclusion. However, a lack of literal basis in the specification for a negative limitation may not be sufficient to establish a prima facie case for lack of descriptive support. Ex parte Parks, 30 USPQ2d 1234, 1236 (Bd. Pat. App. & Inter. 1993). "Rather, as with positive limitations, the disclosure must only 'reasonably convey[] to those skilled in the art that the inventor had possession of the claimed subject matter as of the filing date.' ... While silence will not generally suffice to support a negative claim limitation, there may be circumstances in which it can be established that a skilled artisan would understand a negative limitation to necessarily be present in a disclosure." Novartis Pharms. Corp. v. Accord Healthcare, Inc., 38 F.4th 1013, 2022 USPQ2d 569 (Fed. Cir. 2022) (quoting Ariad Pharm. Inc. v. Eli Lilly & Co., 589 F.3d 1336, 1351, 94 USPQ2d 1161, 1172). In this case, Lee teaches a step of negative selection of CD3-CD14-CD19- cells may be performed prior to contacting with the first culturing medium. See, e.g., paragraphs 25, 75; claim 21. Lee does not explicitly disclose the negative limitation recited by claim 1: “wherein a negative selection of CD3-CD19-CD14- is not performed on the mononuclear cells prior to the contact step.” However, since Lee describes that the negative selection of CD3-CD19-CD14- cells may be performed prior to contacting with the first culturing medium in one embodiment of the disclosed invention, the disclosure reasonably conveys to ordinary skill in the art that such a step of negative selection is optional and may be excluded from the disclosed process. Therefore, one of ordinary skill in the art would have understood that the negative limitation of claim 1 is necessarily present in the Lee disclosure. For these reasons, the Lee disclosure is found to anticipate the negative limitation of claim 1, prior to the effective filing date of the instantly claimed invention. Accordingly, claim 1 is anticipated by the prior art. Regarding dependent claim 2, Lee teaches the mononuclear cells are derived from peripheral blood, cord blood or bone marrow. See, e.g., paragraphs 11, 17; claim 9. Regarding dependent claim 3, Lee teaches the first and second culturing medium comprises a hematopoietic cell medium. See, e.g., paragraphs 18, 22; claims 10, 16. Regarding dependent claim 4, Lee teaches the hematopoietic cell medium comprises AIM-V™ medium. See, e.g., paragraphs 18, 22; claims 11, 17. Regarding dependent claim 5, Lee teaches the first culturing medium comprises a serum protein. See, e.g., paragraphs 19, 23; claims 12, 18. Regarding dependent claim 6, Lee teaches the first culturing medium comprises human platelet lysate. See, e.g., paragraphs 19, 23; claim 13, 19. 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. Claims 1-6 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-12 of U.S. Patent No. 12,195,759 B2. Although the claims at issue are not identical, they are not patentably distinct from each other because the patent claims anticipate the instant claims. The reference claims recite a method, comprising obtaining mononuclear cells from a subject; contacting the mononuclear cells with a first culturing medium comprising IL-15, IL-12 and IL-18 for about 3-6 days to obtain a cultured cell population; and contacting the cultured cell population with a second culturing medium comprising IL-15 and IL-12 for about 3-6 days after contacting with the first culturing medium. See reference claims 1, 8. The reference claims further cite the process produces a pharmaceutical composition for treating cancer (claims 2-3), and the mononuclear cells are obtained from a subject with cancer (claim 5). Instant claim 1 further recites that a negative selection of CD3-CD19-CD14- is not performed on the mononuclear cells prior to the contact step. This limitation is anticipated by the reference claims for at least the following reasons: MPEP 2173.05(i) instructs: Any negative limitation or exclusionary proviso must have basis in the original disclosure. If alternative elements are positively recited in the specification, they may be explicitly excluded in the claims. See In re Johnson, 558 F.2d 1008, 1019, 194 USPQ 187, 196 (CCPA 1977) ("[the] specification, having described the whole, necessarily described the part remaining."). See also Ex parte Grasselli, 231 USPQ 393 (Bd. App. 1983), aff’d mem., 738 F.2d 453 (Fed. Cir. 1984). In describing alternative features, the applicant need not articulate advantages or disadvantages of each feature in order to later exclude the alternative features. See Inphi Corporation v. Netlist, Inc., 805 F.3d 1350, 1356-57, 116 USPQ2d 2006, 2010-11 (Fed. Cir. 2015). The mere absence of a positive recitation is not basis for an exclusion. However, a lack of literal basis in the specification for a negative limitation may not be sufficient to establish a prima facie case for lack of descriptive support. Ex parte Parks, 30 USPQ2d 1234, 1236 (Bd. Pat. App. & Inter. 1993). "Rather, as with positive limitations, the disclosure must only 'reasonably convey[] to those skilled in the art that the inventor had possession of the claimed subject matter as of the filing date.' ... While silence will not generally suffice to support a negative claim limitation, there may be circumstances in which it can be established that a skilled artisan would understand a negative limitation to necessarily be present in a disclosure." Novartis Pharms. Corp. v. Accord Healthcare, Inc., 38 F.4th 1013, 2022 USPQ2d 569 (Fed. Cir. 2022) (quoting Ariad Pharm. Inc. v. Eli Lilly & Co., 589 F.3d 1336, 1351, 94 USPQ2d 1161, 1172). In this case, the reference claims do not explicitly recite the negative limitation recited by instant claim 1: “wherein a negative selection of CD3-CD19-CD14- is not performed on the mononuclear cells prior to the contact step.” However, only dependent reference claim 12 recites a step of negative selection of CD3-CD14-CD19- cells is performed prior to contacting with the first culturing medium. Therefore, since reference claim 12 is dependent upon and necessarily limiting the method of reference claim 8, one of ordinary skill in the art would have understood that the negative selection step is not required by reference claim 8, and, therefore, the negative selection step may be excluded from the method according to reference claim 8. Accordingly, the reference claims would have reasonably conveyed to one of ordinary skill in the art that the negative limitation of instant claim 1 is necessarily present in at least reference claim 8. For these reasons, the reference claims are found to anticipate the negative limitation of instant claim 1. Therefore, instant claim 1 is anticipated by the reference claims. Regarding instant claim 2, the patent claims recite the mononuclear cells are derived from peripheral blood, cord blood or bone marrow. See claims 6, 9. Regarding instant claim 3, the patent claims recite the first and second culturing medium comprises a hematopoietic cell medium. See claims 1, 8. Regarding instant claim 4, the claim recites the hematopoietic cell medium comprises AIM-V™ medium. As set forth above under 35 U.S.C. 112(b), the scope of claim 4 is indefinite for reciting the trademark AIM-V™. For the sake of compact prosecution, a hematopoietic cell culture medium comprising at least IL-15 and IL-12, as found in the reference claims, will be treated as reading on the limitations of instant claim 4. Regarding instant claim 5, the patent claims recite the first culturing medium comprises a serum protein. See claims 1, 8. Regarding instant claim 6, the patent claim recite the first culturing medium comprises human platelet lysate. See claims 10-11. Conclusion Any inquiry concerning this communication or earlier communications from the examiner should be directed to JAMES J GRABER whose telephone number is (571)270-3988. The examiner can normally be reached Monday-Thursday: 9:00 am - 4:00 pm. 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 D 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. /JAMES JOSEPH GRABER/Examiner, Art Unit 1631
Read full office action

Prosecution Timeline

Feb 17, 2023
Application Filed
Feb 27, 2026
Non-Final Rejection — §102, §112, §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
46%
Grant Probability
99%
With Interview (+57.3%)
3y 9m
Median Time to Grant
Low
PTA Risk
Based on 181 resolved cases by this examiner. Grant probability derived from career allow rate.

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