DETAILED ACTION
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 .
Claim Status
In the reply filed 15 July 2026, Applicant has amended claim 1. Claims 2 and 5 are cancelled. Therefore, 1, 3-4 are herein pending.
Priority
This application was filed 02/20/2024 and is a 371 application of PCT/CN2021/115503 filed on 08/31/2021, which claims benefit to the foreign application CN202110959221.1 filed on 08/20/2021.
In the reply filed 15 July 2026, applicant filled a certified English translation of CN202110959222.1 is acknowledged. Therefore, application is obtained the benefit of foreign priority under 35 U.S.C. 119(a)-(d) prior to declaration of an interference.
Thus, the earliest possible priority for the instant application is 08/20/2021.
Withdrawn of Rejections
Applicant has cancelled the claim 5, therefore, the prior rejection of claim 5 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ) is moot.
Maintained Claim Rejections - 35 USC § 103
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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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.
Claims 1, 3-4 are stand rejected in modified form under 35 U.S.C. 103 as being unpatentable over Chae et al., (Oncotarget. 2018; 9: 4301-17, cited in IDS filed 03/27/2024; hereinafter “Chae”), in view of Yi et al. (Medicine & Public Health, Chinese Selected Doctoral Dissertations and Master's Theses Full-Text Databases (Master's) No. 2., 15 February 2021, cited in “Translation of the ISR” of PCT/CN2021/115503 filed 23.02.2023; hereinafter “Yi”), and Kaseko et al., (US20120088304A1, Pub. Date: Apr. 12, 2012; cited in PTO892; hereinafter “Kaseko”) and Drexler et al. (Leukemia. 1996 Apr;10(4):588-99; cited in IDS filed 08/08/2025; hereinafter “Drexler”). This rejection is maintained for reasons of record and current applicants’ amendments.
Regarding claims 1, 3 and 4, Chae teaches a culture medium for Human acute myeloid leukemia cells (h-AML) culture comprises a 1% glutamine additive, human IL-6 (20 ng/ml), human IL-3 (20 ng/ml), recombinant human FLT3 (100 ng/ml) and human SCF (100 ng/ml). Furthermore, Chae teaches that the culture medium for h-AML further comprising RPMI-1640 and streptomycin/penicillin (p. 4313 “cell culture” ¶ and “Hematopoietic cell colony assays” ¶).
Still, Chae is silent to human macrophage colony-stimulating factor (G-CSF) and IL-7 comprises in h-AML cells culture medium. However, such was known in the prior art.
Yi teaches that glutamic acid (which is a non-essential amino acid) and G-CSF (100ng/ml) can be used in conjunction with Flt-3L (equivalent to FLT3 Ligand), IL-6, and IL3 for primary cell culture of chronic myeloid leukemia cells (see page 5, section 1.2); and primary cells of chronic myeloid leukemia cells and primary cells of acute myeloid leukemia are myeloid primary cells.
Kaseko teaches culture myelogenous leukemia cells (i.e., K-562 cell) with culture medium (RPMil 640, 10% FCS, 10 IU/ml penicillin, 10 pg/ml streptomycin, and 1 mmol/L L-glutamine) and further supplemented with 1% non-essential amino acids, 10 ng/ml of human IL-7 and 100 U/ml of human (IL-2 [0286] of Kaseko).
Furthermore, Drexler discloses that in combinations of FLT3 with G-CSF, GM-CSF, M-CSF, IL-3, SCF with IL-3, IL-6 and/or IL-7 had synergistic or additive mitogenic effects on primary AML and ALL cells proliferation (abstract of Drexler). Therefore, it would also be easy for a person skilled in the art to conceive of using a glutamine additive, a non-essential amino acid, interleukin-7 and a macrophage colony stimulating factor as components of a culture medium for primary human acute myeloid leukemia cells, and selecting a human-derived component or a corresponding recombination factor is merely a conventional selection which can be readily made. Therefore, it would be easy to arrive at the technical solution set forth in claim 1 by combining Chae, Yi and Kaseko teaching.
MPEP 2143 (A) states that combining prior art elements according to known methods to yield predictable results. The rationale to support a conclusion that the claim would have been obvious is that all the claimed elements were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combination yielded nothing more than predictable results to one of ordinary skill in the art. KSR, 550 U.S. at 416, 82 USPQ2d at 1395. Accordingly, it would have been obvious to practice the culture medium of Chae and include a glutamine additive, a non-essential amino acid, interleukin-7 and a macrophage colony stimulating factor as components of a culture medium for primary human acute myeloid leukemia cells as taught by Yi and Kaseko with a reasonable expectation of success. The POSITA would have been motivated at the time of filing to do so as taught by Yi and Kaseko because Drexler teaches that combinations of FLT3 with G-CSF, GM-CSF, M-CSF, IL-3, SCF with IL-3, IL-6 and/or IL-7 had synergistic or additive mitogenic effects on primary AML and ALL cells proliferation (abstract of Drexler). The POSITA would have had a reasonable expectation of success in combining the teachings of Chae and Yi and Kaseko because each of these teachings both successfully generated culture medium for h-AML cells. Therefore, the products and method as taught by Chae et al. in view of Yi and Kaseko et al. would have been prima facie obvious over the products and method of the instant application. In regard to the reasonable expectation of success in doing so, IL-7 and G-CSF the culture medium of Chae had a reasonable expectation of success since the steps thereof required no more than pipetting the appropriate concentration of each component (factors) and cell culture technology.
Regarding amended claim 1, the concentration of a glutamine additive, non-essential amino acid(s), human interleukin-6, human interleukin-7, human interleukin-3, recombinant human FLT3 Ligand, recombinant human macrophage colony-stimulating factor, and human stem cell factor in the culture medium over Chae, in view of Yi and Kaseko does not particularly teach the limitation. However, it would have been obvious to a person skilled in the art to use a sufficient amount of factors in the culture medium as taught by Chae, in view of Yi and Kaseko to stimulate the AML and ALL cells proliferation in order to obtain desired yield of the AML with a reasonable expectation of success. MPEP 2144.05 II (A) states that Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). In here, the amount of factor is merely a conventional wide range selection in the culture medium and would be routinely optimizable. Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical (see the response to argument below).
Hence, the claimed invention as a whole was prima facie obvious in the absence of evidence to the contrary.
RESPONSE TO ARGUMENTS
Applicant's arguments and declaration under 37 CFR §1.132 filed on 15 July 2026 are acknowledged.
Applicant argues that the art cited does not teach the factors of canceled claim 2, now Claim 1. Perforce, this same art does not and cannot "recognize" these factors as ones to be optimized. See remark p. 7 4th ¶.
Applicants’ arguments have been fully considered but they are not persuasive.
MPEP 2145 states 35 U.S.C. § 103(a) based test for obviousness is not whether the features of a secondary reference may be bodily incorporated into the structure of the primary reference; nor is it that the claimed invention must be expressly suggested in any one or all of the references. Rather, the test is what the combined teachings of the references would have suggested to those of ordinary skill in the art. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981).
In here, as discussed above, Chae et al. in view of Yi and Kaseko et al teaches the recited factors of claim 1 for culturing the h-AML cells. Therefore, a person of ordinary skill in the art would have had a reasonable expectation of success in combining the teachings of Chae and Yi and Kaseko because each of these teachings both successfully preparation and/or use of culture medium for culturing h-AML cells. Therefore, the claimed product e.g., the culture medium comprising all the factors recited in amended claim 1 for culturing h-AML cells would have been prima facie obvious over Chae et al. in view of Yi and Kaseko et al, particularly, in the absence of persuasive evidence demonstrating that the combined medium factors would not be optimizable. Therefore, the evidence of record does not establish that the claimed culture medium factors produces an unexpected or surprising h-AML cells relative to what would have been reasonably expected from the combined teaching of Chae, Yi and Kaseko.
In particular, incorporating the additionally recited culture-medium factors at a suitable concentration would have involved no more than routine cell culture techniques such as combining known media components and adjusting their concentration through ordinary experimentation. POSITA therefore would have had a reasonable expectation that the resulting culture medium would be suitable for culturing recited h-AML cells.
Applicant remark that in his Declaration, co-inventor Yu Ying He prepared, and then compared, the culture mediums of Chae et al. (Comparative Example 1) and Fei Yiwen (Comparative Example 2) as against that which is claimed. As evidenced in the Declaration, the culture medium claimed had unexpectedly superior proliferation, higher heterogeneity, and a higher level of success rate of cultivation than that obtained with the cited prior art (see Figs. 2A, 2B). This evidence is clearly demonstrative of non-obviousness which, when taken alone or in concert with the defective rejection against the subject matter of Claim 2, is now incorporated into Claim 1. See remark p. 7 and declaration 4-7¶.
The Applicant's arguments have been fully considered, but is not persuasive because
in the 7th ¶ of declaration, the Applicant has prepared “medium of invention” using the culture medium comprising Basal medium (10% (v/v) fetal bovine serum + 100 ng/mL Primocin), 0.5 mM glutamine additive, 9 ng/mL human SCF, 5.67 ng/mL human IL-6, 51 ng/mL hIL-3, 27ng/ml hFLT3L, 50uM non-essential amino acids, 17 ng/mL human IL-7, and 27 ng/mL h-CSF. Therefore, the factors of medium of invention are very specific that has been compared with the culture medium disclosed in Chae et al (example 1) and culture medium for primary disclosed in Fei (example 2). The factors of amended claim 1 culture medium are wide range such as human SCF in the culture medium is 1 ng/mL to 81 ng/mL. Therefore, the specific factors that are used in medium of invention are not commensurate in scope.
in the 4-7th ¶ of declaration the “medium of invention” (with a very specific factors) has been compared with the culture medium disclosed in Chae et al (example 1) and culture medium for primary disclosed in Fei (example 2). However, the based test for obviousness is not whether the features of a secondary reference may be bodily incorporated into the structure of the primary reference; nor is it that the claimed invention must be expressly suggested in any one or all of the references. Rather, the test is what the combined teachings of the references would have suggested to those of ordinary skill in the art. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981). In here, as discussed above, a person of ordinary skill in the art would have had a reasonable expectation of success in combining the teachings of Chae and Yi and Kaseko because each reference teaches the successful preparation and/or use of culture medium for culturing h-AML cells. Therefore, a POSITA would have reasonably expected that a culture medium combining the factors taught in example 1 and 2 of the Declaration would provide cell proliferation comparable to that obtained with the “medium of invention” as reflected in Fig. 2A and 2B of the Declaration, particularly, in the absence of persuasive evidence demonstrating that the combined medium would produce materially different proliferation. Therefore, the evidence of record does not establish that the claimed culture medium produces an unexpected or surprising proliferative effect relative to what would have been reasonably expected from the combined teaching of Chae, Yi and Kaseko.
Applicant further has compared the proliferation result of “medium of invention” with individually example 1 and example 2. Therefore, Applicant did not compare the results to the closest prior art, which would be a combination of the prior art references of Chae, Yi and Kaseko. Instead, Applicant compared their results to the individual prior art references.
MEPE 716.02(e) states “Showing unexpected results over one of two equally close prior art references will not rebut prima facie obviousness unless the teachings of the prior art references are sufficiently similar to each other that the testing of one showing unexpected results would provide the same information as to the other. In re Johnson, 747 F.2d 1456, 1461, 223 USPQ 1260, 1264 (Fed. Cir. 1984) (Claimed compounds differed from the prior art either by the presence of a trifluoromethyl group instead of a chloride radical, or by the presence of an unsaturated ester group instead of a saturated ester group. Although applicant compared the claimed invention with the prior art compound containing a chloride radical, the court found this evidence insufficient to rebut the prima facie case of obviousness because the evidence did not show relative effectiveness over all compounds of the closest prior art. An applicant does not have to test all the compounds taught by each reference, "[h]owever, where an applicant tests less than all cited compounds, the test must be sufficient to permit a conclusion respecting the relative effectiveness of applicant’s claimed compounds and the compounds of the closest prior art." Id. (quoting In re Payne, 606 F.2d 303, 316, 203 USPQ 245, 256 (CCPA 1979)) (emphasis in original).).”
Accordingly, the claimed culture medium has not been shown an unexpected or superior proliferative effect relative to what would have been reasonably expected from combined teaching of Chae, Yi and Kaseko.
Conclusion
Applicants’ amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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 date of this final action.
No claims are allowed.
Examiner Contact Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MASUDUR RAHMAN whose telephone number is (571)272-0196. The examiner can normally be reached M-F 8-5 (EST).
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/MASUDUR RAHMAN/ Patent Examiner, Art Unit 1633
/JEREMY C FLINDERS/ Primary Examiner, Art Unit 1684
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