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 .
Election/Restriction
Applicant’s election without traverse of Group I (Claims 1-12, 21-29) and (CD19 species) in the reply filed on November 14, 2025 is acknowledged. Claims 15-17, and 20 (Group II) and Species II-III (Claims 16-17) were subsequently canceled by applicants. The non-elected species of Species I are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species of Species Group I, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on November 14, 2025.
Claim Objections
Claims 1-3,11-12,21,29 are objected to because of the following informalities: Claims 1-3,11-12,21, and 29 recite culturing the cells in a “culture media.” Only one medium is used to culture the cells at a time, not several (media). Therefore, culture media (plural) should be changed to medium in the claims. Appropriate correction 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 3,6,8-12 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 3 recites a process in which NK (natural killer) cells undergo expansion at multiple stages in different culture media. It is not clear if the interleukin medium components (IL-2,IL-12, and IL-18) are required in the first expansion step, the 2nd expansion step, or required in all expansion steps. For purposes of examination, the examiner will interpret the claim to mean that at least one expansion step has the medium components required.
Claim 6 is indefinite because it is unclear if the first population, the second population, or both populations of feeder cells are required to be K562 cells. Claim 6 only refers to one feeder cell population.
Claim 8 recites, “wherein the repeated co-culturing increases the cytotoxicity or persistence of the expanded NK cell.” There are two populations of expanded NK cells. The first expanded population is referred to as “the expanded population” which results from the first expansion culturing stage. The second expanded population is referred to in claim 1 as “a further expanded population of NK cells.” Only the second expanded population/”a further expanded population of NK cells” would be exposed to repeated co-culturing not the expanded population of NK cells which only undergoes one expansion culture step.
Claim 9 is indefinite because it is not clear which population of natural killer cells is contacted with a vector encoding a chimeric antigen receptor. Dependent claim 10 fails to further clarify this issue.
Claims 11 and 12 are indefinite because it is unclear which medium is required to possess the interleukin components recited in claims 11-12. One cannot determine if the interleukins are in the first expansion medium, the second expansion medium, or both. For purposes of examination, the examiner will interpret the claims to mean that at least one culture medium must have the interleukins recited in the claims. Claims 11 and 12 are also indefinite because they use the term “less than about.” This term is indefinite because “about” means that the amount can be the stated value, less than the stated value, or greater than the stated value. This conflicts with the term “less than” recited in the claims because “about” means that the amount can be the stated value or more than the stated value.
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 1,4-12,21,23,25-26, and 28 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Trager (US 20220411754)
Trager discloses
A method for enhancing the expansion of natural killer (NK) cells comprising:
Co-culturing, in a culture media, a population of NK cells with a first population of feeder cells for a first period of time, wherein the first feeder cell population comprises cells engineered to express 4-IBBL and membrane-bound interlerukin-15 (mbIL15), wherein the population of NK cells comprise fewer cells than the first population of feeder cells, wherein the culture media comprises interleukin 2 (IL2) and one of interleukin 12 (IL12) and interleukin 18 (IL18), and wherein the co-culturing for the first period of time results in an expanded population of NK cells (Paragraphs 5-6,10-13, and 84 of Trager):
Separating after the first period of time, at least a portion of the expanded population of NK cells from the first population of feeder cells (Paragraph 20,47, and 53); and
Co-culturing, in fresh culture media, the at least a portion of the expanded population of NK cells with a second population of the feeder cells for a second period of time, wherein the at least a portion of the expanded population of NK cells comprise fewer cells than the second population of feeder cells, wherein the culture media comprises interleukin 2 (IL2), interleukin 12 (IL12), and interleukin 18 (IL18), and wherein the co-culturing for the second period of time results in a further expanded population of NK cells (Paragraphs 20-23,87-91 of Trager) as in instant Claim 1.
Trager further discloses wherein the population of NK cells is present in a an amount between about 5 and about 25 times less than the population of feeder cells at inception of each co-culturing (Paragraph 91 of Trager) as in instant Claim 4. Trager discloses wherein the expanded NK cells are separated from the feeder cells by Fluorescence-activated Cell Sorting (FACS) (Paragraphs 47 and 118 of Trager) as in instant Claim 5. Trager discloses wherein the feeder cell population comprises K562 cells (Paragraphs 11,84,97,110, and 114 of Trager) as in instant Claim 6. Trager discloses wherein the repeated co-culturing increases expression of markers of NK cell activation (Paragraph 31,43-44 of Trager) as in instant Claim 7. Trager discloses wherein the repeated co-culturing increases cytotoxicity or persistence of the expanded NK cells (Paragraph 2 of Trager) as in instant Claim 8. Trager discloses contacting the NK cells with a vector encoding a chimeric antigen receptor (CAR) (Paragraphs 7 and 16) as in instant Claim 9. Trager discloses wherein the CAR binds to one or more CD19,CD123,CD70,BCMA, or a ligand of the natural killer receptor group D (NKG2D) (Paragraph 16 of Trager) as in instant Claim 10. Trager discloses wherein (i) the IL2 is present in the medium at a concentration of less than about 50 units/mL; (ii) if the IL12 is present in the media, the IL12 is at a concentration less than about 30 ng/mL, and (iii) if the IL18 is present in the media, the IL18 is at a concentration of less than about 10 ng/mL (Paragraphs 12-13 and 23 of Trager) as in instant Claim 11. Trager discloses wherein (i) the IL2 is present in the medium at a concentration between about 20 units/mL and about 50 units/mL, (Paragraph 94 of Liu) (ii) if the IL12 is present in the media, the IL12 is at a concentration between about 15 ng/mL and about 30 ng/mL; and (iii) if the IL18 is present in the media, the IL18 is at a concentration of less than about 5 ng/mL (Paragraphs 10-13 and 18-19,21,23 of Trager) as in instant Claim 12.
Trager discloses
The method of enhancing the expansion of natural killer (NK) cells comprising:
Co-culturing, in a culture media, a population of NK cells with a first population of feeder cells for a first period of time, wherein the first feeder cell population comprises cells engineered to express 4-1BBL and membrane-bound interleukin-15 (mbIL15) (Paragraph 11 of Trager), wherein the population of NK cells comprises fewer cells than the first population of feeder cells, wherein the culture media comprises interleukin 2(IL2) and one of interleukin 12, and interleukin 18 (IL18) (Paragraphs 10-13,18-19,21,23,84), wherein the IL2 is present in the media in a concentration between about 0.5 ng/mL and about 6.0 ng/mL (Paragraphs 10-13,18-19,21,23,75), wherein if the IL12 is present in the media, the IL12 is at a concentration between about 10 ng/mL and about 100 ng/mL(Paragraphs 10-13,18-19,21,23 of Trager), and wherein if the IL18 is present in the media, the IL18 is at a concentration between about 0.01 ng/mL and about 30 ng/mL, and wherein the co-culturing for the first period of time results in an expanded population of NK cells (Paragraphs 10-13,18-19,21,23,78,84 of Trager);
Separating, after the first period of time, at least a portion of the expanded population of NK cells from the first population of feeder cells (Paragraphs 47,87-88,118 of Trager); and
Co-culturing in first culture media, the at least a portion of the expanded population of NK cells with a second population of the feeder cells for a second period of time, wherein the at least portion of the expanded population of NK cells comprise fewer cells than the second population of feeder cells, wherein culture media comprises interleukin 2 (IL2), and one of interleukin 12 (IL12), and interleukin 18 (IL18), wherein the co-culturing for the second period of time results in a further expanded population of NK cells (10-13,22, 23,87-90) as in instant Claim 21.
Trager further teaches wherein the population of NK cells is derived from peripheral blood (Paragraph 84) as in instant Claim 23 and 26. Trager further teaches wherein the method results in at least 100,000 fold to 5,000,000 fold expansion of NK cells (Paragraphs 28,35,94,113) as in instant Claims 25 and 28.
The reference anticipates the claim limitations.
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 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 1-12,21-23,25-26,28-29 are rejected under 35 U.S.C. 103 as being unpatentable over Trager (US 20220411754)
Trager applies as above to teach claims 1,4-12,21,23,25-26, and 28. Trager teaches two main expansion steps and does not teach repeating the separating and co-culturing steps a total of 3 times or more using fresh medium containing IL2, IL12, and IL-18. However, expanding the natural killer cells would merely be considered a duplication of steps. In this case, duplicating the expansion steps would be desirable in order to produce more natural killer cells. MPEP 2144.04 (B.Duplication of Parts) In reHarza, 274 F.2d 669, 124 USPQ 378 (CCPA 1960) (Claims at issue were directed to a water-tight masonry structure wherein a water seal of flexible material fills the joints which form between adjacent pours of concrete. The claimed water seal has a “web” which lies in the joint, and a plurality of “ribs” projecting outwardly from each side of the web into one of the adjacent concrete slabs. The prior art disclosed a flexible water stop for preventing passage of water between masses of concrete in the shape of a plus sign (+). Although the reference did not disclose a plurality of ribs, the court held that mere duplication of parts has no patentable significance unless a new and unexpected result is produced.).
Therefore, multiple expansion processes is merely duplication of parts and does not carry patentable weight. Therefore, repeating the separating and the co-culturing steps at least one additional time using fresh culture media comprising IL2 and one of IL12 and IL18, thereby resulting in additional expansion of the further expanded population of NK cells would have been obvious as in instant Clams 2 and 29. Trager further teaches wherein: (i) the IL2 is present in the media at a concentration between about 10 units/mL and about 100 units/ml: (ii) if the IL12 is present in the media, the IL12 is at a concentration between about 10 ng/ml and about 100 ng/mL; and (iii) if the IL18 is present in the media, the IL18 is at a concentration between about 0.01 ng/mL and about 30 ng/mL, wherein each of the first and second periods of time is about 7 days(Paragraphs 6,10-13,18-19,21-23,36,75-78 of Trager) , and wherein the co-culturing is repeated at least three times (duplication of parts) as in instant Claim 3. Trager teaches wherein each of the first and the second periods of time is about 7 days (Paragraph 35 of Trager), and wherein the co-culturing is repeated at least three times (duplication of parts) as in instant Claim 22.
Trager does not specifically state multiple repeating expansion steps besides two. An artisan would have been motivated to have had multiple expansion steps in order to produce as many natural killer cells as possible. Given the teachings of the cited references and the level of skill of an ordinary skilled artisan at the time of applicant’s invention, it must be considered, absent evidence to the contrary, that the ordinary skilled artisan would have had a reasonable expectation of success in practicing the claimed invention.
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 combinations would have yielded predictable results to one of ordinary skill in the art at the time of the invention (See KSA International Co. v. Teleflex Inc., 82 USPQ2d 1385 (U.S. 2007). People of ordinary skill in the art will be highly educated individuals, possessing advanced degrees, including M.D.s and Ph.D.s. They will be medical doctors, scientists, or engineers. Thus, these people most likely will be knowledgeable and well-read in the relevant literature. These people will have practical knowledge in molecular biology and immunology. Therefore, the level of ordinary skill in the art is high.
Claims 1-12,21-29 are rejected under 35 U.S.C. 103 as being unpatentable over Childs (US 20180057795) in view of Kerbauy (US 20200390816)
Childs teaches a method for enhancing the expansion of natural killer (NK) cells comprising:
Co-culturing, in a culture media, a population of NK cells with a first population of feeder cells for a first period of time, wherein the population of NK cells comprise fewer cells than the first population of feeder cells, wherein the culture media comprises interleukin 2 (IL2) (Paragraphs 6-7,103-104 of Childs) at a IL-2 concentration of 10-2000 IU/ml (Paragraphs 12-14 of Childs), and wherein the co-culturing for the first period of time results in an expanded population of NK cells (Paragraphs 12-14,91-93,103 of Childs). This period of this expansion time can last 1-14 days (Paragraph 103):
Childs teaches that NK cells/NK cell subsets can be successfully isolated using flow sorting/FACS. An artisan would have been motivated to have used such as separation procedure in order to ensure that only NK cells were present in the population of cells. Childs teaches that FACs specifically is used to separate and analyze the NK cells from the other cells present (Paragraphs 12-13, 77; Paragraph 98 of Childs); and
Co-culturing, in fresh culture media, the at least a portion of the expanded population of NK cells with a second population of the feeder cells for a second period of time, wherein the at least a portion of the expanded population of NK cells comprise fewer cells than the second population of feeder cells (Paragraphs 93 and 116-117 of Child), wherein the culture media comprises interleukin 2 (IL2) (Paragraphs 6-7 of Childs) at a concentration of 500 IU/ml (Paragraphs 12-14 of Childs), and wherein the co-culturing for the second period of time results in a further expanded population of NK cells (Paragraphs 20-21 of Childs). Childs teaches an expansion periods that last 1-50 days (Paragraph 90 of Childs). In Childs embodiment, these cells are transduced with a vector that can encode for chimeric antigen receptor (Paragraph 90 of Childs).
Childs does not teach the inclusion of IL-12 or IL-18 in Childs’ culture medium. Kerbauy teaches that medium containing IL-2,IL-12,IL-18 can be used to further expand NK cells (Paragraphs 3,5,8). Kerbauy teaches that the concentration of IL-18 can be at a concentration of 10-100 ng/ml and IL-12 can be at a concentration of 0.1-150 ng/mL (Paragraph 8 of Kerbauy) In paragraph 11 of Kerbauy, the concentration of IL-2 can be present at a concentration of 10-500 U/ml. The expansion stage can last 5-20 days (Paragraph 10 of Kerbauy). It would have been obvious to an artisan of ordinary skill at the time of effective filing to have used these interleukins in an expansion medium to further expand natural killer cells because these cytokines not only assist with NK expansion, they also assist with pre-activating the cells so that they are more cytotoxic against unwanted targets such as tumors (Abstract, Paragraphs 3,5, and 8 of Kerbauy). There would have been a high expectation for success using IL-2, IL-18, AND IL-12 in an expansion medium since Kerbauy teaches that such cytokines promote expansion of natural killer cells (Abstract, Paragraphs 3,5, and 8 of Kerbauy) as in instant Claims 1,3,11-12,21.
MPEP § 2144.05 (II) states “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 reAller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) (Claimed process which was performed at a temperature between 40°C and 80°C and an acid concentration between 25% and 70% was held to be prima facie obvious over a reference process which differed from the claims only in that the reference process was performed at a temperature of 100°C and an acid concentration of 10%.); see also Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382 (“The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages.”); In reHoeschele, 406 F.2d 1403, 160 USPQ 809 (CCPA 1969) (Claimed elastomeric polyurethanes which fell within the broad scope of the references were held to be unpatentable thereover because, among other reasons, there was no evidence of the criticality of the claimed ranges of molecular weight or molar proportions.). For more recent cases applying this principle, see Merck & Co. Inc.v.Biocraft Lab. Inc., 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir.), cert. denied, 493 U.S. 975 (1989); In reKulling, 897 F.2d 1147, 14 USPQ2d 1056 (Fed. Cir. 1990); and In re Geisler, 116 F.3d 1465, 43 USPQ2d 1362 (Fed. Cir. 1997); Smith v. Nichols, 88 U.S. 112, 118-19 (1874) (a change in form, proportions, or degree “will not sustain a patent”); In re Williams, 36 F.2d 436, 438 (CCPA 1929) (“It is a settled principle of law that a mere carrying forward of an original patented conception involving only change of form, proportions, or degree, or the substitution of equivalents doing the same thing as the original invention, by substantially the same means, is not such an invention as will sustain a patent, even though the changes of the kind may produce better results than prior inventions.”). See also KSR Int' l Co. v. Teleflex Inc., 550 U.S. 398, 416 (2007) (identifying “the need for caution in granting a patent based on the combination of elements found in the prior art.”)”
A review of the specification failed to provide evidence that the claimed concentrations are critical. Absent such evidence, it would have been obvious to an artisan of ordinary skill at the time of effectively filing Kerbauy to try a finite number of possible concentrations of IL-2,IL-12, and IL-18 to predictably arrive at the claimed concentration of interleukins through routine optimization. An artisan would have a reasonable expectation of success in optimizing the concentrations because determining preferred concentrations of each interleukin to add to the medium was long established in the art as demonstrated by Kerbauy. Thus, Kerbauy renders the instantly claimed concentration above as in instant Claims 3, 11-12,21.
Furthermore, artisan would have been motivated to have carried out further expansion steps in order to produce more NK cells. MPEP 2144.04 (B.Duplication of Parts states the following: “In reHarza, 274 F.2d 669, 124 USPQ 378 (CCPA 1960) (Claims at issue were directed to a water-tight masonry structure wherein a water seal of flexible material fills the joints which form between adjacent pours of concrete. The claimed water seal has a “web” which lies in the joint, and a plurality of “ribs” projecting outwardly from each side of the web into one of the adjacent concrete slabs. The prior art disclosed a flexible water stop for preventing passage of water between masses of concrete in the shape of a plus sign (+). Although the reference did not disclose a plurality of ribs, the court held that mere duplication of parts has no patentable significance unless a new and unexpected result is produced.).” Therefore, multiple expansion processes is merely duplication of parts and does not carry patentable weight as in instant Claims 2-3,22,29. Furthermore, duplicating the number of expansion processes for the natural killer cells would result in at least a 100,000 fold to 5,000,000 fold expansion of NK cells as in instant Clams 25 and 28.
Dependent Claims taught by Childs
Childs teaches that the NK cells are activated, transduced, and expanded in the presence of feeder cells wherein the ratio of feeder cells: NK cells is at least 2:1,5:1; 10:1, 15:1, 20:1 (Paragraph 92 of Childs) as in instant Claim 4. Childs teaches wherein the expanded NK cells are separated from feeder cells by Fluorescence-activated Cell Sorting (FACS) (Paragraphs 20-21 of Childs) as in instant Claim 5. Childs teaches wherein the feeder cell population comprises K562 cells (Paragraph 117 of Childs) as in instant Claim 6. Childs teaches wherein the repeated co-culturing increases expression of markers of NK cell activation (Paragraphs 118 and 120 of Child) as in instant Claim 7. Childs teaches wherein the repeated co-culturing increases cytotoxicity or persistence of the expanded NK cells (Paragraphs 118 and 120 of Child) as in instant Claim 8. Childs teaches contacting the NK cells with a vector encoding a chimeric antigen receptor (CAR) (Paragraphs 122-123 of Child) as in instant Claim 9. Childs teaches wherein the CAR binds to CD19 (Paragraph 123 of Child) as in instant Claim 10. Childs teaches wherein the population of NK cells is derived from peripheral blood (Paragraphs 138 and 169 of Childs) as in instant Claims 23 and 26.
Dependent Claims taught by Kerbauy
Kerbauy teaches that the cells can be derived from peripheral blood (Paragraph 53 of Kerbauy) as in instant Claims 23 and 26. Kerbauy teaches that the cells can be derived from umbilical cord blood (Paragraph 53 of Kerbauy) as in instant Claims 24 and 27.
Childs teaches a process involving two expansion phases that successfully produces large quantities of natural killer cells. Although Childs teaches the use of IL-2 in Childs’ expansion protocol, Childs does not further include IL12 or IL18 in the expansion medium. However, an artisan would have been motivated to have included such cytokines since Kerbauy teaches that such cytokines can also successfully promote expansion of natural killer cells. Given the teachings of the cited references and the level of skill of an ordinary skilled artisan at the time of applicant’s invention, it must be considered, absent evidence to the contrary, that the ordinary skilled artisan would have had a reasonable expectation of success in practicing the claimed invention.
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 combinations would have yielded predictable results to one of ordinary skill in the art at the time of the invention (See KSA International Co. v. Teleflex Inc., 82 USPQ2d 1385 (U.S. 2007). People of ordinary skill in the art will be highly educated individuals, possessing advanced degrees, including M.D.s and Ph.D.s. They will be medical doctors, scientists, or engineers. Thus, these people most likely will be knowledgeable and well-read in the relevant literature. These people will have practical knowledge in molecular biology and immunology. Therefore, the level of ordinary skill in the art is high.
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 1-3,6,10-12,21, and 29 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 69,75-76,95, and 99 of copending Application No. 17/628,105 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of 17/628,105 are species of Application 18/024,012. The main difference between the claim 69 of 17/628,105 and claim 1 Application 18/024,012 (the instant application) is that claim 1 of Application 18/024,012 does not require contacting the NK cells with a vector encoding a chimeric antigen receptor (CAR) (Claim 69 of Application 17/628,105). Claim 75 of Application 17/628,105 corresponds to instant claim 6. Claim 76 of Application 17/628,105 corresponds to instant claim 10. Claim 95 of Application 17/628,105 corresponds to instant claims 3 and 11-12,21. Claim 99 of Application 17/628,105 corresponds to instant claims 1-3,11-12, and 21,29.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1,3-4,10-12,21,23-24,26-27 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 60-65,68,71,73-74 of copending Application No. 18,291,826 (reference application) in view of Kerbauy (US 20200390816). Although the claims at issue are not identical, they are not patentably distinct from each other because claims 60 of Application 18/291,826 expands NK cells by placing the NK cells with feeder cells capable of expressing 4-1BBL and membrane bound interleukin-15 in a culture medium that includes IL12 and IL18. Independent claim 60 does not teach the inclusion of IL-2; however, IL-2 is briefly mentioned in dependent claim 65. Furthermore, Kerbauy teaches that IL-2 can be used in the expansion of NK cells and provides preferred concentration ranges of IL-2. Thus, the limitations for instant claims 1 and 21 are disclosed. An artisan would have been motivated to have included the recited concentrations of IL-2 taught by Kerbauy since such concentrations can successfully result in expansion of NK cells. Claims 61-62 of Application 18/291,826 corresponds to instant claim 4. Claims 63-65 of Application 18/291,826 corresponds to instant claims 3,11-12,21. Claim 64 corresponds to instant claims 3,11-12,21. Claim 65 corresponds to instant clams 3,11-12, and 21. Claims 68 and 71 of Application 18/291,826 corresponds instant claim 10. Claim 73 (peripheral blood source) of Application 18,291,826 corresponds to instant claim 23 and 26. Claim 74 (cord blood) of Application 18,291,826 correspond to claims 24 and 27. This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
All claims stand rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to LAUREN K VAN BUREN whose telephone number is (571)270-1025. The examiner can normally be reached M-F:9:30am-5:40pm; 9:00-10:00pm.
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LAUREN K. VAN BUREN
Examiner
Art Unit 1638
/Tracy Vivlemore/Supervisory Primary Examiner, Art Unit 1638