Prosecution Insights
Last updated: April 17, 2026
Application No. 16/495,083

METHODS FOR ISOLATING, EXPANDING AND ADMINISTERING CANCER SPECIFIC CD8+ T CELLS

Final Rejection §103
Filed
Sep 17, 2019
Examiner
BELYAVSKYI, MICHAIL A
Art Unit
1644
Tech Center
1600 — Biotechnology & Organic Chemistry
Assignee
National Institutes Of Health (Nih) U S Dept Of Health And Human Services (Dhhs) U S Government
OA Round
7 (Final)
64%
Grant Probability
Moderate
8-9
OA Rounds
3y 1m
To Grant
91%
With Interview

Examiner Intelligence

Grants 64% of resolved cases
64%
Career Allow Rate
697 granted / 1091 resolved
+3.9% vs TC avg
Strong +27% interview lift
Without
With
+27.2%
Interview Lift
resolved cases with interview
Typical timeline
3y 1m
Avg Prosecution
77 currently pending
Career history
1168
Total Applications
across all art units

Statute-Specific Performance

§101
2.3%
-37.7% vs TC avg
§103
29.0%
-11.0% vs TC avg
§102
9.7%
-30.3% vs TC avg
§112
10.9%
-29.1% vs TC avg
Black line = Tech Center average estimate • Based on career data from 1091 resolved cases

Office Action

§103
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 APPLICANT’S AMENDMENT 1. Applicant’s amendment filed on 07/17/25 is acknowledged. 2. Claims 1, 14-16, 23, 24, 29, 33-35, 38 are pending. Claims 23 and 24 stand withdrawn from further consideration by the Examiner, 37 C.F.R. § 1.142(b) as being drawn to nonelected inventions. Claims 1, 14-16, 29, 33-35 read on the method to isolate and expand cancer-specific CD8+ T cells are under consideration in the instant application. 3. 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. 4. Claims 1, 14-16, 29, 33-35 stand rejected under 35 U.S.C. 103 as being unpatentable over US Patent Application 20130302278, Adlard et al.,( Inter. J of Cancer, 2014, v.135, pages 820-829), US Patent Application 20180169224 in view of US Patent Application 20180177816, Hayashi et al ( PNAS, 2009, v.106 pages 2764-2769 and newly cited Greisen et al (Frontiers in Immunol, 2017, v.8 page 1-14) for the same reasons set forth in the previous Office Action, mailed on 01/17/25. Applicant’s arguments filed on 10/03/24 have been fully considered but have not been found convincing. Applicant asserts that : (i) as amended the claims now recited that isolated cancer -specific CD8+ T cells are expanded without the use of tumor-specific antigen. None of the prior art references disclosed said feature; (ii) the ability to treat a patient without having to biopsy and characterize/isolate tumor antigens for the use is a significant medical breakthrough that provides an unprecedented utility to oncologist. As initial matter, it is noted that the instant claims are not drawn to a method for treat a patient without having to biopsy and characterize/isolate tumor antigens, but rather to the in vitro method for isolating and expanding cancer specific CD8+ T cells. With regards to Applicant’s statement that “amend claims now recited that isolated cancer -specific CD8+ T cells are expanded without the use of tumor-specific antigen. None of the prior art references disclosed said feature” The instant specification clearly teaches that culturing isolated cancer specific CD8+ T cells in the presence of EVs results clonal expansion cancer specific CD8+ T cells. ( see the instant specification page 2, lines 18-21) Thus it is the Examiners position that co-culturing isolated cancer specific CD8+T cell in the culture medium in the presence of EVs would result in expanding said cancer specific CD8+ T cells without the use of tumor-specific antigen. Mere recognition of latent properties in the prior art does not render nonobvious an otherwise known invention. In re Wiseman, 201 USPQ 658 (CCPA 1979). Granting a patent on the discovery of an unknown but inherent function would remove from the public that which is in the public domain by virtue of its inclusion in, or obviousness from, the prior art. In re Baxter Travenol Labs, 21 USPQ2d 1281 (Fed. Cir. 1991). See M.P.E.P. 2145. As has been stated previously, Greisen et al., et al. explicitly teach that co-culturing lymphocytes in the presence of EVs increased proliferation of lymphocytes. Moreover, as has been stated previously, the presence of extracellular vesicles that can be collected and used for various purposes in the culture medium comprising cancer-specific CD8+ T cells were well known in the art before the effective filing date of the claimed invention as taught by US Patent Application 20180177816 ( see entire document claims and Summary of invention in particular). Thus it would be conventional and within the skill of the art to collect extracellular vesicles ( exosomes) from the culture medium comprising cancer-specific CD8+ T cells and use it in the method taught by US Patent Application’ 278 , Adlard et al., US Patent Application’ 224 with a reasonable expectation of success because the prior art suggests that co-culturing lymphocytes with EVs increase proliferation and thus expansion of lymphocytes. US Patent Application’ 278 teaches a method of isolating cancer-specific CD8+ T cells from the mammalian after administering to said mammalian a composition comprising TLR7 agonist ( see entire document paragraphs 0045, 0092, 0163, 0167, 0184 in particular) Adlard et al., teach a method of isolating cancer-specific CD8+ T cells from the mammalian after administering to said mammalian a composition comprising TLR7 agonist ( see entire document, Abstract in particular). US Patent Application’ 224 teaches a method of isolating cancer-specific CD8+ T cells from the mammalian after administering to said mammalian a composition comprising TLR7 agonist ( see entire document paragraphs 0042, 0055, 0057, 0060, 0073 in particular in particular). Hayashi et al ( PNAS, 2009, v.106 pages 2764-2769) teach the use of synthetic TLR7 agonist, such as SM360320 or 1V136 or 1V270 for administering to mammal was well known to one skilled in the art and routinely used. All the claimed elements were known in the prior art and one skill in the art could have combine the elements as claimed by known methods with no change in their respective function and the combination would have yield predictable results to one of ordinary skill in the art at the time of the invention ( see KSR International Co v Teleflex Inc., 550U.S.-, 82 USPQ2d 1385, 2007). Thus, the Examiner reiterated his position that although , US Patent Application’ 278 , Adlard et al., US Patent Application’ 224 does not explicitly teaches the use of TLR7 agonist comprising 1V270, or SM360320 or 1V136, TLR7 agonists were well know to one skill in the art and thus would be conventional and within the skill of the art to determine the optimum type of TLR7 agonist for administration. Further, it has been held that where the general conditions of a claim are disclosed in the prior art, discovering the optimum or workable ranges involves only routine skill in the art. In re Aller, 220 F2d 454,456,105 USPQ 233; 235 (CCPA 1955). see MPEP § 2144.05 part II A. Claim 5 is include because said functional properties would be an obvious properties of TLR7 agonist because the prior art and the instant claims administered the same compound. If the prior art structure is capable of performing the intended use, then it meets the claim. For example in Atlas Powder Co. V. IRECO, 51 USPQ2d 1943 (Fed. Cir. 1999); the following was noted. “Artisans of ordinary skill may not recognize the inherent characteristics or functioning of the prior art. However, the discovery of a previously unappreciated property of a prior art composition, or of a scientific explanation for the prior art’s functioning, does not render the old composition patentably new to the discoverer. “ The Court further held that “this same reasoning holds true when it is not a property but an ingredient which is inherently contained in the prior art”. See MPEP 2112.02. Also, see Bristol-Myers Squibb Co. v. Ben Venue Laboratories, Inc. 58 USPQ2d 1508 (CA FC 2001); Ex parte Novitski 26 USPQ 1389 (BPAI 1993); Mehl/Biophile International Corp. V. Milgraum, 52 USPQ2d 1303 (Fed. Cir. 1999); Atlas Powder Co. V. IRECO, 51 USPQ2d 1943 (Fed. Cir. 1999). Claims 15 and 16 are included because it would be conventional and within the skill of the art to determine the optimum means of administration. Further, it has been held that where the general conditions of a claim are disclosed in the prior art, discovering the optimum or workable ranges involves only routine skill in the art. In re Aller, 220 F2d 454,456,105 USPQ 233; 235 (CCPA 1955). see MPEP § 2144.05 part II A. It is well settled that "discovery of an optimum value of a result effective variable in a known process is ordinarily within the skill of the art." In re Boesch, 617 F.2d 272, 276, 205 USPQ 215, 219 (CCPA 1980). See also Merck & Co. v. Biocraft Labs. Inc., 874 F.2d 804, 809, 10 USPQ2d 1843, 1847-48 (Fed. Cir. 1989) (determination of suitable dosage amounts in diuretic compositions considered a matter of routine experimentation and therefore obvious). From the combined teaching of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary. 5. Claims 1, 38 stand rejected under 35 U.S.C. 103 as being unpatentable over US Patent Application 20130302278, Adlard et al.,( Inter. J of Cancer, 2014, v.135, pages 820-829), US Patent Application 20180169224 in view of US Patent Application 20180177816, , Hayashi et al ( PNAS, 2009, v.106 pages 2764-2769 and Greisen et al (Frontiers in Immunol, 2017, v.8 page 1-14) as applied to claims 1, 14-16, 29, 33-35 and further in view of US Patent Application 20170266297 and US Patent Application 20130202629. The teaching of US Patent Application 20130302278, Adlard et al., US Patent Application 20180169224 , US Patent Application 20180177816, , Hayashi et al and Greisen et al ., has been discussed supra. The teaching of US Patent Application 20130302278, Adlard et al., US Patent Application 20180169224 , US Patent Application 20180177816, , Hayashi et al and Greisen et al., do not explicitly teach TLR7 agonist conjugated to phospholipid moiety. US Patent Application’ 297 teaches a conjugate comprising TLR7 agonist attached to phospholipid moiety. US Patent Application’ 297 teaches that said conjugate enhance the therapeutic properties of TLR7 agonist ( see entire document, paragraph 0516 in particular) US Patent Application’ 629 teaches a conjugate comprising TLR7 agonist attached to phospholipid moiety. US Patent Application 629 teaches that said conjugate enhance the therapeutic properties of TLR7 agonist ( see entire document, paragraphs 0005, 0020, 0110, 0119 in particular) All the claimed elements were known in the prior art and one skill in the art could have combine the elements as claimed by known methods with no change in their respective function and the combination would have yield predictable results to one of ordinary skill in the art at the time of the invention ( see KSR International Co v Teleflex Inc., 550U.S.-, 82 USPQ2d 1385, 2007). Thus it would have been obvious to one of the ordinary skill in the art at the time the invention was made to use conjugate comprising TLR7 agonist attaches to phospholipid moiety in the method of isolating and expanding cancer-specific CD8+ T cells taught by US Patent Application 20130302278, Adlard et al., US Patent Application 20180169224 , US Patent Application 20180177816, , Hayashi et al and Greisen et al with a reasonable expectation of success because the prior art suggests that attachment of phospholipid to enhance the therapeutic properties of TLR7 agonist. From the combined teaching of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary. 6. THIS ACTION IS MADE FINAL. See MPEP § 609(B)(2)(i). 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 extension fee 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. 7. No claim is allowed. 8. Any inquiry concerning this communication or earlier communications from the examiner should be directed to Michail Belyavskyi whose telephone number is 571/272-0840. The examiner can normally be reached Monday through Friday from 9:00 AM to 5:30 PM. A message may be left on the examiner's voice mail service. If attempts to reach the examiner by telephone are unsuccessful, the examiner's supervisor, Daniel Kolker can be reached on 571/ 272-3181 The fax number for the organization where this application or proceeding is assigned is 571/273-8300 Information regarding the status of an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only. For more information about the PAIR system, see http://pair-direct.uspto.gov. Should you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). /MICHAIL A BELYAVSKYI/Primary Examiner, Art Unit 1644
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Prosecution Timeline

Sep 17, 2019
Application Filed
Jun 24, 2022
Non-Final Rejection — §103
Aug 16, 2022
Response Filed
Sep 12, 2022
Final Rejection — §103
Dec 08, 2022
Response after Non-Final Action
Jan 19, 2023
Request for Continued Examination
Jan 29, 2023
Response after Non-Final Action
May 10, 2023
Final Rejection — §103
Jul 17, 2023
Response after Non-Final Action
Aug 16, 2023
Request for Continued Examination
Aug 20, 2023
Response after Non-Final Action
Sep 11, 2023
Non-Final Rejection — §103
Mar 15, 2024
Response Filed
Apr 01, 2024
Final Rejection — §103
Oct 03, 2024
Request for Continued Examination
Oct 07, 2024
Response after Non-Final Action
Jan 13, 2025
Non-Final Rejection — §103
Jul 17, 2025
Response Filed
Aug 04, 2025
Final Rejection — §103
Apr 06, 2026
Response after Non-Final Action

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

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Prosecution Projections

8-9
Expected OA Rounds
64%
Grant Probability
91%
With Interview (+27.2%)
3y 1m
Median Time to Grant
High
PTA Risk
Based on 1091 resolved cases by this examiner. Grant probability derived from career allow rate.

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