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
1. Claims 40-58 are pending.
Claims 40-58 read on a method for manufacturing T cells are under consideration in the instant application.
2. 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.
3. Claims 40-58 stand rejected under 35 U.S.C. 103 as being unpatentable over US Patent Application 20170216356 , US Patent Application 20200407681, US Patent Application 20200085929 , US Patent Application 20210268083 , US Patent Application 20210106655, US Patent Application 20180326032 and US Patent Application 20180333434 in view of US Patent Application 20170037369 , US Patent Application 20160158359 ,US Patent Application 20160122782, US Patent Application 20220152100 and US Patent Application 20020064874 for the same reasons set forth in the previous Office Action, mailed on 09/04/25.
Applicant’s arguments filed on 03/4/26 have been fully considered but have not been found convincing.
Applicant asserts that : (i) most of the prior art references suggest culturing a T cells in the culture medium in the presence of IL-2 and IL-7: (ii) none of the prior art references teaches or suggests any benefits in specially excluding exogenously added IL-2 and IL-7 and inclusion IL-15. (iii) Applicant have demonstrated unexpected results that shows that culturing T cells in the presence of IL-15 without exogenously added Il-2 reduces expression of exhaustion markers (example 6 of the present Specification).
Contrary to Applicant’s assertion it is noted that it has been recently stated that KSR forecloses the argument that a specific teaching, suggestion, or motivation are required to support a finding of obviousness See Board decision ( see KSR International Co v Teleflex Inc., 550U.S.-, 82 USPQ2d 1385, 2007).
Moreover, the Examiner disagrees with Applicant’s interpretation of the prior art references.
The question whether a reference ‘teaches away’ from the invention is inapplicable to an obviousness analysis. In this regard it is noted that according to MPEP § 2123, “[d]isclosed examples and preferred embodiments do not constitute a teaching away from a broader disclosure or nonpreferred embodiments. In re Susi, 440 F.2d 442, 169 USPQ 423 (CCPA 1971). ‘A known or obvious composition does not become patentable simply because it has been described as somewhat inferior to some other product for the same use.' In re Gurley, 27 F.3d 551, 554, 31 USPQ2d 1130, 1132 (Fed. Cir. 1994)…”
It is the Examiner’s position that none of the prior art references teach or suggest absolute requirement of the presence of IL-2 and IL-7 in the culture medium for culturing T cells.
Moreover, as is evidence from the teaching of US Patent 20180371057 and US Patent Application 20110300179 at the time the invention was made one skill in the art would know that culturing T cell in the culture medium with various combinations of cytokines including without IL-2 and /or IL-7 and in the presence of IL-15 can effect the properties of the cells including increase of the persistence , stability and improving immunotherapy ( see US Patent Application’057 paragraph 0045 and US Patent Application’ 179 paragraph 0027 in particular).
With regards to Applicant’s statement of unexpected results.
Evidence of unexpected results must be weight against evidence supporting prima facie obviousness in making a final determination of the obviousness of the claimed invention. In re May, 574 F.2D 1082 197 USPQ 601 (CCPA 1978). When the unexpected properties of the claimed invention are not shown to have a significance equal to or greater than the expected properties, the evidence of unexpected properties may not be sufficient to rebut the evidence of obviousness. In re Nolan, 553 F.2D 1261,1267,193,USPQ 641,645 (CCPA, 1977) ( see MPEP 716.02( c ).
The data shown in Example 6 only shows that culturing in the presence of IL-15 reduces expression of exhausting markers during long term ex-vivo culturing compare to expansion in the presence of IL-2.
However, said results are not unexpected as the prior art teach that T cells can be cultured in the culture medium without adding IL-2 and/or IL-7 ( see above and below ).
As has been stated previously, US Patent Application ‘356 teaches a method of expanding T cells comprising culturing said cells for at least 5 days in the culture medium comprising IL-15. US Patent Application ‘356 teaches that said culture medium might also comprise IL-2, IL-7 and IL-21. US Patent Application ‘356 teaches that prior to expanding T cells are culturing in the culture medium comprising anti-CD3 and anti-CD28 antibody ( see entire document, paragraphs 0104 0240 and claims in particular).
US Patent Application ‘681 teaches a method of expanding T cells including CD45RA+ comprising culturing said cells for at least 5 days in the culture medium comprising IL-15. US Patent Application ‘681 teaches that said culture medium might also comprise IL-2, IL-7 and IL-21. US Patent Application ‘681 teaches that prior to expanding T cells are culturing in the culture medium comprising anti-CD3 and anti-CD28 antibody ( see entire document, paragraphs 0012, 0018, 0052, 0057 in particular).
US Patent Application ‘929 teaches a method of expanding T cells , comprising culturing said cells for at least 5 days in the culture medium comprising IL-15. US Patent Application ‘681 teaches that said culture medium can also comprise IL-2, IL-7 and IL-21. US Patent Application ‘681 teaches that prior to expanding T cells are culturing in the culture medium comprising anti-CD3 and anti-CD28 antibody ( see entire document, paragraphs 0081, 0123 in particular).
US Patent Application ‘083 teaches a method of expanding T cells , comprising culturing said cells for at least 5 days in the culture medium comprising IL-15. US Patent Application ‘681 teaches that said culture medium can also comprise IL-2, IL-7 and IL-21. US Patent Application ‘681 teaches that prior to expanding T cells are culturing in the culture medium comprising anti-CD3 and anti-CD28 antibody ( see entire document, paragraphs 0017, 0132, 0133, 0135 in particular).
US Patent Application ‘655 teaches a method of expanding memory T cells comprising culturing said cells in the culture medium comprising only IL-15. US Patent Application ‘655 teaches that IL-15 alone can significantly stimulate proliferation of memory T cells. ( emphases added, see entire document paragraph 0006 in particular). US Patent Application ‘655 teaches that IL-15/15Ra complex was more effective than IL-15 alone in stimulating memory T cell maintaining and survival. It is the Examiner’s position that one skill in the art would understand that though the complex of IL15/15Ra was better , US Patent Application ‘655 does teach the use of IL-15 alone as well.
US Patent Application ‘032 teaches a method of expanding genetically modified memory T cells in the culture medium comprising IL-15.( see entire document paragraphs 0042, 0057 and 0059 in particular).
US Patent Application ‘434 teaches a method of expanding genetically modified memory T cells in the culture medium comprising IL-15 or IL-7. US Patent Application ‘434 that IL-15 provided anti-apoptotic activity with a consistent effect in promoting the proliferation of naïve and memory T. US Patent Application ‘434 teaches that T cells can be cultured in the culture medium in the absence of IL-2 or IL-7 ( emphases added see entire document paragraphs 0003, 0005, 0015, 0017 and 0077 in particular).
The instant Specification clearly stated that T cells can be expanded in vitro in the culture medium with or without exogenously added IL-2 and or IL-7 ( see the Instant Specification, paragraphs 8-11)
Thus, it is the Examiner’s position that it would be conventional and within the skill of the art to determine an optimal culturing medium with or without IL2 and/or IL-7 for expanding memory T cells. 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).
US Patent Application 20170216356 , US Patent Application 20200407681, US Patent Application 20200085929 , US Patent Application 20210268083 , US Patent Application 20210106655, US Patent Application 20180326032 and US Patent Application 20180333434 do not explicitly teach depleting cells expressing CD14 , CD25 and enrich for the cells expressing CD62L
US Patent Application ‘369 teaches a method comprising a step of depleting a cells expressing CD14 and enriching for cells expressing CD62L. US Patent Application ‘369 teaches that obtained central memory T cells can be CAR- expressing and to be used for adoptive cell therapy. US Patent Application ‘369 teaches that said central memory T cell can be expanded in the culture medium comprising IL-15 alone in the presence of anti-CD3 and anti-CD28 antibodies. US Patent Application ‘369 teaches that said central memory T cell are CD4+ and some also are CD45RA+ ( see entire document, paragraphs 0004, 0022, 0044, 0045, 0117, 0236, 0300, 0304, 0307, 0308, 0331 in particular).
US Patent Application ‘359 teaches a method comprising a step of depleting a cells expressing CD14 and enriching for cells expressing CD62L. US Patent Application ‘369 teaches that obtained memory T cells can be CAR-expressing to be used for adoptive cell therapy. US Patent Application ‘359 teaches that said central memory T cell can be expanded in the culture medium comprising IL-15 alone in the presence of anti-CD3 and anti-CD28 antibodies. US Patent Application ‘359 teaches that some of said central memory T cell are CD4+ and some are CD45RA+ (see entire document, paragraphs 005,0025, 0082,0111,0115 in particular).
US Patent Application ‘782 teaches a method comprising a step of depleting a cells expressing CD14 and enriching for cells expressing CD62L. US Patent Application ‘782 teaches that obtained memory T cells can be CAR-expressing to be used for adoptive cell therapy. US Patent Application ‘782 teaches that said central memory T cell can be expanded in the culture medium comprising IL-15 alone in the presence of anti-CD3 and anti-CD28 antibodies. US Patent Application ‘782 teaches that said central memory T cell are CD4+ and some are CD45RA+ (see entire document, paragraphs 0051, 0095, 0285, 0286,0305 in particular).
US Patent Application’100 teaches a method of obtaining a population of T cells for adoptive immunotherapy, comprising selectively depleting CD25 -expressing cells. US Patent Application’00 teaches that selective depletion of CD25+ cells results in obtaining a T cells enhanced the immunological competence of the final T cell product ( see entire document, paragraphs 0420, 0423, 0453 in particular).
US Patent Application’874 teaches a method of obtaining a population of T cells for adoptive immunotherapy, comprising selectively depleting CD25 -expressing cells. US Patent Application’874 teaches that selective depletion of CD25+ cells results in obtaining a T cells with enhanced T cell function and increased immunogenic power suitable for adoptive immunotherapy ( see entire document, paragraphs 0050, 0055, 0075 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 to one of ordinary skill in the art before the effective filing date of the claimed invention to treat the sample comprising PBMC to deplete cell expressing CD14, CD25 and enriching for cells expressing CD62L with a reasonable expectation of success because the prior art teach that depleting cell expressing CD14 , CD25 and enriching for cells expressing CD62L results in obtaining T cells with increased functionality and immunogenic power for adoptive cell therapy.
Claims 45- 58 are included because it would be conventional and within the skill of the art to : (i) determine the presence/absence and effective amount of each individual cytokine in the culture medium ; or (ii) determine the optimum means of isolating and duration for culturing T cells, or (iii) optimal percentage of enriched population of CD4 and CD8 cells 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 teachings of the references, it was 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.
"The test of obviousness is not express suggestion of the claimed invention in any or all of the references but rather what the references taken collectively would suggest to those of ordinary skill in the art presumed to be familiar with them." See In re Rosselet, 146 USPQ 183, 186 (CCPA 1965).
6. No claim is allowed.
7. THIS ACTION IS MADE FINAL even though it is a first action in this case. See MPEP § 706.07(b). 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, however, event will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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, Gregory Emch can be reached on 571/ 272-8149
The fax number for the organization where this application or proceeding is assigned is 571/273-8300
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/MICHAIL A BELYAVSKYI/Primary Examiner, Art Unit 1644
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