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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 11/13/2025 has been entered.
Status of the Claims
Claims 1 – 6, 8, 11 – 13, 16, 18 – 27, and 29 were pending. Claims 1 – 6, 8, 11 – 13, 16, 18 – 27, and 29 have been amended; and claims 30 – 33 have been newly added. Claims 1 – 6, 8, 11 – 13, 16, 18 – 27, 29, and 30 – 33 are currently pending and are the subject of this Office Action.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
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.
Previous rejection, withdrawn: claims 1 – 6, 8, 11 – 13, 16, 18 – 24, and 29 were rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for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.
In view of the claim amendments in the reply of 11/13/2025, this rejection is withdrawn.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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.
Previous rejection, withdrawn: claims 1, 3 – 6, 8, 11 – 13, 16, 18, 20, 21, 26, and 27 were rejected under 35 U.S.C. 103 as being unpatentable over WILLIAMS (Williams BA, et al. CD16+NK-92 and anti-CD123 monoclonal antibody prolongs survival in primary human acute myeloid leukemia xenografted mice. Haematologica. 2018 Oct;103(10):1720-1729; an IDS reference submitted 05/18/2021) in view of WU (US 2007/0224201 A1, published 09/27/2007; see PTO-892: Notice of References Cited of 02/12/2025).
In view of the claim amendments of the reply of 11/13/2025, this rejection is withdrawn.
Previous rejection, withdrawn: claims 2 and 22 – 25 were rejected under 35 U.S.C. 103 as being unpatentable over WILLIAMS in view of WU as applied to claims 1, 3 – 6, 8, 11 – 13, 16, 18, 20, 21, 26, and 27 above, and further in view of KLINGEMANN (WO 2018165291 A1, filed 03/07/2018; see PTO-892 of 02/12/2025).
After further consideration, this rejection is withdrawn.
New rejection: claims 1 – 6, 8, 11 – 13, 16, 18, 20 – 27, and 30 are rejected under 35 U.S.C. 103 as being unpatentable over WILLIAMS (Williams BA, et al. CD16+NK-92 and anti-CD123 monoclonal antibody prolongs survival in primary human acute myeloid leukemia xenografted mice. Haematologica. 2018 Oct;103(10):1720-1729; an IDS reference submitted 05/18/2021) in view of WU (US 2007/0224201 A1, published 09/27/2007; see PTO-892: Notice of References Cited of 02/12/2025).
The present application is directed to a population of modified cells expressing CD16 (SEQ ID NO: 1), wherein: (i) the modified cells were derived from an immortalized cytolytic cancer cell line isolated from a non-Hodgkin's lymphoma subject,(ii) the modified cells do not express IL-2, (iii) the population comprises one or more of the modified cells, and (iv) the expression level of CD16 does not decrease or decreases no more than 20% when the modified cells are activated as compared to expression level of CD16 on the modified cells before activation.
According to the present specification, “examples of haNK® cells include IL2 Dependent haNK® cells ("haNK003 cells") and IL2 Dependent haNK® cells the former additionally express recombinant IL-2 and the latter do not. As used herein, the term "NK cells" refer to a) donor derived NK cells, b) NK-92.176V- CD16.ERIL2 cells (i.e., IL2 Independent haNK® cells) and c) NK-92.176V-CD16 cells (i.e., IL2 Dependent haNK® cells)” (p. 10, end of fourth paragraph). Thus, the population of modified cells expressing CD 16 (SEQ ID NO: 1) of the present claims are NK-92.176V-CD16 cells. WILLIAMS discloses gene-modified CD16NK-92 cells (NK-92.176V) (see Introduction, second paragraph). Thus, it is understood that WILLIAMS discloses modified cells similar in structure to the modified cells of the present claims.
WILLIAMS is directed to NK cell lines, NK-92 and CD16+ NK-92, as a treatment for acute myeloid leukemia (AML). CD16+ NK-92 cells express CD16. See abstract. WILLIAMS also discloses “the new haNK platform (CD16+IL-2+NK-92)” implying that CD16+ NK-92 does not express IL-2. See p. 1728, left column. Furthermore, WILLIAMS teaches that “NK-92 which was derived from a patient with an NK-cell lymphoma”. See Introduction, first paragraph.
However WILLIAMS does not expressly disclose the sequence of SEQ ID NO: 1. WU is directed to compositions of matter useful for the diagnosis and treatment of tumor in mammals and to methods of using those compositions. See abstract. WU discloses The primary cells for mediating ADCC, NK cells, express FcγRIII (CD16). See paragraphs 6455 and 6504. Finally, WU discloses the sequence of present SEQ ID NO: 1. See Appendix.
Regarding claim 1, WILLIAMS discloses a population of modified cells expressing CD16, and WU’s SEQ ID NO: 506 is identical to present SEQ ID NO: 1.
Regarding “the expression level of CD16 does not decrease or decreases no more than 20% when the modified cells are activated as compared to expression level of CD 16 on the modified cells before activation” of claim 1 or 6, while WILLIAMS does not expressly state this property, WILLIAMS’ CD16+ NK-92 cells express CD16 which causes the activation of NK-92 cells and thus WILLIAMS’ CD16+ NK-92 cells anticipate this claimed observation. Therefore WILLIAMS’ CD16+ NK-92 cells would inherently achieve an expression level of CD16 that does not decrease or decreases no more than 20% when the modified cells are activated as compared to expression level of CD 16 on the cells before activation. "[T]he 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." Atlas Powder Co. v. IRECO Inc., 190 F.3d 1342, 1347, 51 USPQ2d 1943, 1947 (Fed. Cir. 1999). Thus the claiming of a new use, new function or unknown property which is inherently present in the prior art does not necessarily make the claim patentable. In re Best, 562 F.2d 1252, 1254, 195 USPQ 430, 433 (CCPA 1977). See MPEP 2112(I).
Alternatively, the activation of the modified cells is only suggestive of an intended use of the cells that does not change the structure the modified cells.
Because WILLIAMS discloses CD16+ NK-92 cells that were derived from a patient with lymphoma and are effective at treating tumors and WU discloses a CD16 polypeptide sequence that is effective in activating cytotoxicity for the treatment of tumors, it would have been obvious to one having ordinary skill in the art to produce the population of modified cells expressing CD16 (SEQ ID NO:1) of claim 1 in view of WILLIAMS and WU. There would have been a reasonable expectation of success given that CD16 -expressing modified cells have been shown to successfully treat tumors as evidenced by the applied prior art.
Regarding claim 2, although neither WILLIAMS nor WU discloses the nucleic acid sequence of SEQ ID NO: 2, the sequence of SEQ ID NO: 2 encodes WU’s CD16 polypeptide. See Appendix.
It is noted that the courts have found that the disclosure of the polypeptide makes the nucleic acid encoding the protein obvious as the methods of obtaining the nucleic acids are routine in the art and can be obtained with a reasonable expectation of success. See MPEP 2143(E)(Example 3), Ex parte Kubin, 83 USPQ2d 1410 (Bd. Pat. App. & Int. 2007), and In re Kubin 90 USPQ2d 1417 (U. S. Court of Appeals Fed. Cir. 2009).
Regarding claim 3, WILLIAMS discloses that natural killer cells typically express CD16 and are able to mediate ADCC against antibody-coated targets, enabling both adaptive and innate immune responses. See p. 1721, left column, second paragraph.
Regarding claims 4 – 6, WILLIAMS discloses that CD16 mediate antibody-dependent cell-mediated cytotoxicity (ADCC) (see Introduction, p. 1721, left column) which then destroys cancer cells. Although WILLIAMS does not expressly disclose that the modified cells maintain a steady state of cytotoxicity for at least 5 hours from the initiation of the activation, WILLIAMS discloses a significant survival rate increase in acute myeloid leukemia (AML) xenografted mice. See Figure 7B, p. 1728. Because the CD16+ NK-92 cells of WILLIAMS and WU renders the population of modified cells claim 1 obvious as discussed above, they would inherently maintain a steady state of cytotoxicity as recited in claim 4, express higher levels of CD16 than NK cells from the donor as recited in claim 5, and have a percentage of cells that are positive for CD16 that decreases no more than 20% after the cells are activated as compared to the cells before activation of claim 6.
Regarding claims 8 and 16, according to the present specification, “CD16 is an Fc receptor which recognizes and binds to the Fc portion of an antibody to activate NK cells for the ADCC effector mechanism. Because they lack CD16 receptors, unmodified NK-92® cells are unable to lyse target cells via the ADCC mechanism” (paragraph [0004]). WILLIAMS discloses that CD16 negative NK-92 parental line was genetically modified to express the high affinity Fc gamma receptor, enabling antibody-dependent cell-mediated cytotoxicity (see abstract), suggesting that the NK-92 cells disclosed by WILLIAMS are activated. When the prior art discloses a product which reasonably appears to be either identical with or only slightly different than a product claimed in a product-by-process claim, a rejection based alternatively on either section 102 or section 103 of the statute is eminently fair and acceptable. See MPEP 2113 (III).
Regarding claim 11, WILLIAMS discloses the modified NK-92 cells are K562 cells. See Methods: Cell lines and primary samples, p. 1721, left column.
Regarding claims 12 and 13, although WILLAIMS does not expressly state that the disclosed CD16+ NK-92 cells results in a CD16 expression that decreases no more than 10% (of claim 12) or 5% (of claim 13) as compared to the modified NK-92 cells before the activation, WILLIAMS’ CD16+ NK-92 cells anticipate this claimed observation and therefore WILLIAMS’ CD16+ NK-92 cells would inherently achieve a CD16 expression that decreases no more than 10% (of claim 12) or 5% (of claim 13) as compared to the modified cells before the activation.
Regarding claim 18, WILLIAMS discloses E:T ratios of 1:1, 5:1, 10:1, and 25:1. See Figure 1, p. 1722.
Regarding claim 20, WILLIAMS discloses NK-92 cytotoxicity of about 80% at an effector to target ratio of 5:1. See Figure 2A.
Regarding claim 21, WILLIAMS discloses that the gene-modified CD16+NK-92 cells disclosed by WILLIAMS demonstrate ADCC. See Introduction, first and second paragraphs, p. 1721, left column. Regarding “wherein the modified NK-92 cells have ADCC activity of at least 40%” of claim 21, although WILLAIMS does not expressly state that the disclosed CD16+ NK-92 cells results in an ADCC activity of at least 40%, WILLIAMS’ CD16+ NK-92 cells anticipate this claimed observation and therefore WILLIAMS’ CD16+ NK-92 cells would inherently achieve a CD16 expression with an ADCC activity of at least 40%.
Regarding claim 22, WILLIAMS discloses a method of producing a population of modified cells which was derived from a patient with an NK-cell lymphoma” (see Introduction, first paragraph) and WU discloses the sequence of CD16. Thus, it would have been obvious to one having ordinary skill in the art to arrive to the method of producing a population of modified cells of present claim 22.
Regarding claim 23, WU teaches that the nucleic acid (e.g., cDNA or genomic DNA) encoding the polypeptide may be inserted into a replicable vector for cloning (amplification of the DNA) or for expression. Various vectors are publicly available. The vector may, for example, be in the form of a plasmid, cosmid, viral particle, or phage. See paragraph 6609. Thus, WU renders the use of the lentiviral infection obvious. Furthermore, WILLIAMS does not teach the use of antibiotics in the cell culture. See Methods: Cell lines and primary samples, p. 1721, left column.
Regarding claim 24 – 25, WU teaches kits and articles of manufacture comprising at least one antibody, oligopeptide or organic molecule. See paragraph 6667.
Regarding claim 26, WU discloses pharmaceutically acceptable excipients. See paragraph 6424. Because WILLIAMS discloses CD16+NK-92 cells that may be administered to subjects and WU discloses pharmaceutically acceptable excipients, it would have been obvious to one having ordinary skill in the art to formulate WILLIAMS’ NK-92 cells with WU’s pharmaceutical excipients.
Regarding claim 27, WILLIAMS discloses the administration of the NK-92 cells to mice. See Animals, p. 1721, right column.
Regarding claim 30, because the WILLIAMS’ modified cells are similar in structure as that of the claimed modified cells, WILLIAMS’ cells would also exhibit an expression of CD16 on the activated modified cells is no less than 80% of the CD16 expression on the modified cells before the activation as recited on. See MPEP 2112(I).
Response to Arguments
On page 7, second to last paragraph, of the reply of 11/13/2025, Applicant argues that “Williams and Wu, in combination and alone, do not teach or suggest the modified cells of amended claim 1, wherein the "expression level of CD 16 does not decrease or decreases no more than 20% when the modified cells are activated as compared to expression level of CD16 on the modified cells before activation." As discussed previously in the response to Non-Final Office Action filed May 12, 2025, Williams is silent on CD16 expression levels in NK-92 cells before and after cell activation and Wu does not remedy Williams' deficiency in this regard.” Applicant’s argument has been fully considered but not found persuasive because WILLIAMS discloses the structure of the cells of the present claims, and thus WILLIAMS’ cells inherently function as described in the present claims.
Applicant’s argument is not persuasive because the present claim 1 recites an inherent property of a composition known in the art. According to the present specification, “examples of haNK® cells include IL2 Dependent haNK® cells ("haNK003 cells") and IL2 Dependent haNK® cells the former additionally express recombinant IL-2 and the latter do not. As used herein, the term "NK cells" refer to a) donor derived NK cells, b) NK-92.176V- CD16.ERIL2 cells (i.e., IL2 Independent haNK® cells) and c) NK-92.176V-CD16 cells (i.e., IL2 Dependent haNK® cells)” (p. 10, end of fourth paragraph). Thus, the population of modified cells expressing CD16 (SEQ ID NO: 1) of the present claims are understood to be NK-92.176V-CD16 cells. WILLIAMS discloses gene-modified CD16NK-92 cells (NK-92.176V) (see Introduction, second paragraph). Because WILLIAMS’ cells is physically similar to those of present claim 1, WILLAMS’ gene-modified cells would inherently have an expression level of CD 16 that does not decrease or decreases no more than 20% when the cells are activated as compared to expression level of CD 16 on the cells before activation. Alternatively, the activation of the modified cells is only suggestive of an intended use of the cells that does not change the structure the modified cells.
On p. 9, first paragraph, of the reply, Applicant argues that “the actual expression levels of CD16 would be the net effect of both CD16 expression and degradation. William is silent on the actual CD16 expression levels before and after cell activation, and it does not contemplate CD16 degradation at all. One cannot assume that CD16 expression levels will remain high simply because a cell contains a transgene to express it, much less remaining at the claimed level. While it is not impossible that the cells of Williams maintain high CD16 expression levels before and after activation as recited in amended claim 1, such a feature is not necessarily present in the cells of Williams. Accordingly, the Examiner has not met the high standard required for applying an obviousness rejection based on inherency.”
Applicant’s argument is not persuasive because there is no requirement that a person of ordinary skill in the art would have recognized the inherent disclosure at the relevant time, but only that the subject matter is in fact inherent in the prior art reference. See MPEP 2112 (II). Although WILLIAMS may not expressly state the recited properties of the claimed modified cells, the structure of WILLIAMS’ cells is the same as the structure of the claimed modified cells and would thus WILLIAMS’ cells would have the same properties.
On page 9, of the reply, Applicant argues that “the claimed population of NK-92 cells and the claimed methods of producing said population of cells satisfy a long-felt and unmet need for modified cells with the enhanced property of maintaining high CD16 expression level, which enables a high steady state of cytotoxicity against target tumor cells.”
Applicant’s argument is not persuasive because WILLIAMS teaches that NK-92 cell line lacks the Fc gamma receptor IIIA (CD16), typically expressed by NK cells and, therefore, cannot mediate antibody-dependent cell-mediated cytotoxicity (ADCC); however, gene-modified CD16NK-92 cells (NK-92.176V and NK-92.176V.GFP) demonstrate ADCC. See Introduction, first and second paragraphs. Thus, WILLIAMS teaches modified NK cells expressing CD16 that exhibit cytotoxicity. Because WILLIAMS’ gene-modified CD16NK-92 cells (NK-92.176V) is similar to the claimed modified cells of the present claims, WILLIAMS’ cells satisfy a long-felt and unmet need for modified cells with the enhanced property of maintaining high CD16 expression level, which enables a high steady state of cytotoxicity against target tumor cells.
On p. 10, second paragraph, of the reply, Applicant argues that “[i]n contrast, the modified cells of the current claims are ready for direct use in cancer patients. The cells provide the benefit of maintaining CD16 in patients without the additional method steps or the extra costs of additional reagents. Prior to administration to patients, the cells do not need modification with a mutant CD16 transgene that can't be cleaved by ADAM17. Further, after the cells are administered to patients, there is no need to additionally administer ADAM17 inhibitors to patients.
Applicant’s argument is not persuasive because it is not commensurate in scope with present claims. The present claims do not recite limitations that distinguish the structure of the modified cells from those of the cited references. Thus, the cited references render the present claims obvious.
On page 11, last paragraph – p. 12, first paragraph, of the reply, Applicant argues that “[t]he combination of Williams and Wu does not teach or suggest a method of producing a population of modified cells as recited in amended claim 22, wherein ‘the expression of CD16 on the activated modified cells is no less than 50% of the CD16 expression on the modified cells before the activation.’ Klingemann does not remedy this deficiency”
The rejection over WILLIAMS in view of WU and in further view of KLINGEMANN has been withdrawn. Claims 2 and 22 – 25 are presently rejected over WILLIAMS in view of WU for the reasons discussed under the 103 rejection above.
Previous rejection; maintained in modified form: claims 19, 29, 32 – 33 are rejected under 35 U.S.C. 103 as being unpatentable over WILLIAMS in view of WU as applied to claims 1, 3 – 6, 8, 11 – 13, 16, 18, 20, 21, 26, and 27 above, and further in view of MA (US 2018/0187149 A1, published 07/05/2018; see PTO-892 of 02/12/2025).
The teachings of WILLIAMS and WU with regard to claim 1, from which claim 19 and 29, either directly or indirectly depend, are discussed above and are fully incorporated here.
Although WILLIAMS and WU render the population of modified cells expressing CD16 (SEQ ID NO: 1) of present claim 1 obvious as discussed above, and WU discloses the amino acid sequence of SEQ ID NO: 1, neither WILLIAMS nor WU discloses that the modified NK-92 cells additionally express a chimeric antigen receptor (CAR) and/or a suicide gene.
However, MA discloses NK-92 cells that express a CAR and/or a suicide gene. MA is directed to an engineered cell comprising a first CAR and a second CAR wherein the engineered cells is an NK-92 cell. See claims 1 and 12.
Regarding claims 19, 29, and 32 – 33, MA discloses that the engineered cell includes an inducible suicide gene (“safety switch”) which greatly increases safety profile and limits on-target or off-tumor toxicities of the compound CARs. The “safety switch” may be an inducible suicide gene, such as, without limiting, caspase 9 gene, thymidine kinase, cytosine deaminase (CD) or cytochrome P450. See paragraph 0134.
Because WILLIAMS discloses CD16+ NK-92 cells which express CD16 but not IL-2 that are effective at treating tumors and WU discloses a CD16 polypeptide sequence that is effective in activating cytotoxicity for the treatment of tumors, and MA discloses that the NK-92 cells may further include a CAR and suicide gene for improved efficacy and safety for the subject, it would have been obvious to one having ordinary skill in the art to modify WILLIAMS and WU’s CD16+ NK-92 cells with MA’s CAR and suicide gene.
Response to Arguments
On page 12, last paragraph, of the reply, Applicant argues that “the combination of Williams and Wu does not teach or suggest a population of modified cells as recited in amended claim 1, wherein ‘the expression level of CD16 does not decrease or decreases no more than 20% when the modified cells are activated as compared to expression level of CD16 on the modified cells before activation.’ Also as discussed above, the inherency allegation regarding Williams is unfounded. Further as discussed above, the combination of Williams and Wu does not teach or suggest a population of modified cells as recited in amended claim 22, wherein ‘the expression of CD16 on the activated modified cells is no less than 50% of the CD16 expression on the cells before the activation.’ Ma does not remedy these deficiencies.”
Applicant’s argument is not persuasive because WILLIAMS in view of WU renders a population of modified cells expressing CD 16 (SEQ ID NO: 1) of present claim 1 obvious as discussed above, and MA discloses NK-92 cells that express a CAR and/or a suicide gene. Thus, it would have been obvious to one having ordinary skill in the art to add a CAR and/or a suicide gene, which MA teaches, to WILLIAMS and WU’s modified NK-92 cells.
New rejection: claim 31 is rejected under 35 U.S.C. 103 as being unpatentable over WILLIAMS in view of WU as applied to claims 1 – 6, 8, 11 – 13, 16, 18, 20 – 27, and 30 and further in view of SHADPOUR (Shadpour H, et al. Enrichment and expansion of cells using antibody-coated micropallet arrays. Cytometry A. 2009 Jul;75(7):609-18; see PTO-892 submitted with this Office Action).
According to the present specification, “V176-CD16 expressing cells were enriched using a purified anti-human CD16 Antibody (BioLegend, catalog #302002) and anti-mouse IgG MicroBeads from Miltenyi (catalog #130-048-401) following manufacturer's instructions.”
SHADPOUR is directed to the use of an antibody that specifically bind a cell surface receptor for the positive selection of specific cells. See Abstract: Methods. SHADPOUR teaches that antibody-based pre-enrichment in combination with micropallet-based cell selection will be a valuable tool for isolation and expansion of rare cells from small heterogeneous populations. See Abstract: Conclusions. Thus, it would have been obvious to one having ordinary skill in the art to enrich for the modified cells after the introduction of the nucleic acid encoding CD16 in order to isolate the CD16-expressing cells as SHADPOUR teaches.
Regarding part (ii) of claim 31, WILLIAMS discloses the contacting of the modified cells comprising CD16 with IL-2. See Methods: Cell lines and primary samples, p. 1721, left column.
Because WILLIAMS teaches CD16+ NK-92 cells that are effective at treating tumors, WU discloses a CD16 polypeptide sequence that is effective in activating cytotoxicity for the treatment of tumors, and SHADPOUR teaches how to enrich a population of modified cells in culture for better isolation of the modified cells, it would have been obvious to one having ordinary skill in the art to modify the method of culturing WILLIAMS and WU’s CD16+ NK-92 cells with SHADPOUR’s enrichment step to arrive to the invention of present claim 31. There would have been a reasonable expectation of success considering that cultured CD16+ NK-92 cells are known to successfully treat tumors as evidenced by the applied art.
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.
Previous rejection, maintained: claims 1 – 6, 8, 11 – 13, 16, 18 – 27, and 29 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 – 7, 12 – 16, and 19 - 21 of copending Application No. 17/115,360 (reference application).
Although the claims at issue are not identical, they are not patentably distinct from each other because copending claim 1 recites a method for generating a clonal population of transfected NK-92 cells, comprising: transfecting NK-92 cells with a multi-cistronic nucleic acid vector comprising a positive selection marker and at least one transgene, wherein the positive selection marker is endoplasmic-reticulum IL2 (ER-IL2) having the sequence recited in SEQ ID NO: 1, or endoplasmic-reticulum IL 15 (ER-IL15) having the sequence recited in SEQ ID NO: 2; culturing the transfected NK-92 cells in a cell culture medium in absence of IL-2; diluting the cultured NK-92 cells by clonal dilution, in absence of IL-2, . . ..
Copending claim 4 recites wherein the at least one transgene encodes an Fc Receptor . . .
Copending claim 5 recites that the Fc Receptor is CD 16.
Thus, the present claims are anticipated by the copending claims.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
Claims 1 – 6, 8, 11 – 13, 16, 18 – 27, 29, and 30 – 33 are rejected.
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/ESTELLA M. GUSTILO/Examiner, Art Unit 1646
/PETER J REDDIG/Primary Examiner, Art Unit 1646
APPENDIX
Alignment with SEQ ID NO: 1
US-10-529-351A-506
Filing date in PALM: 2006-05-24
Sequence 506, US/10529351A
Publication No. US20070224201A1
GENERAL INFORMATION
APPLICANT: THOMAS D. WU
APPLICANT: ZEMIN ZHANG
TITLE OF INVENTION: COMPOSITIONS AND METHODS FOR THE DIAGNOSIS AND
TITLE OF INVENTION: TREATMENT OF TUMOR
FILE REFERENCE: P5101R1-US
CURRENT APPLICATION NUMBER: US/10/529,351A
CURRENT FILING DATE: 2005-03-25
PRIOR APPLICATION NUMBER: PCT/US03/28547
PRIOR FILING DATE: 2003-09-29
PRIOR APPLICATION NUMBER: US 60/414,971
PRIOR FILING DATE: 2002-10-02
NUMBER OF SEQ ID NOS: 6355
SEQ ID NO 506
LENGTH: 254
TYPE: PRT
ORGANISM: Homo sapiens
ALIGNMENT:
Query Match 100.0%; Score 1359; Length 254;
Best Local Similarity 100.0%;
Matches 254; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 MWQLLLPTALLLLVSAGMRTEDLPKAVVFLEPQWYRVLEKDSVTLKCQGAYSPEDNSTQW 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 MWQLLLPTALLLLVSAGMRTEDLPKAVVFLEPQWYRVLEKDSVTLKCQGAYSPEDNSTQW 60
Qy 61 FHNESLISSQASSYFIDAATVDDSGEYRCQTNLSTLSDPVQLEVHIGWLLLQAPRWVFKE 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 FHNESLISSQASSYFIDAATVDDSGEYRCQTNLSTLSDPVQLEVHIGWLLLQAPRWVFKE 120
Qy 121 EDPIHLRCHSWKNTALHKVTYLQNGKGRKYFHHNSDFYIPKATLKDSGSYFCRGLVGSKN 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 EDPIHLRCHSWKNTALHKVTYLQNGKGRKYFHHNSDFYIPKATLKDSGSYFCRGLVGSKN 180
Qy 181 VSSETVNITITQGLAVSTISSFFPPGYQVSFCLVMVLLFAVDTGLYFSVKTNIRSSTRDW 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 VSSETVNITITQGLAVSTISSFFPPGYQVSFCLVMVLLFAVDTGLYFSVKTNIRSSTRDW 240
Qy 241 KDHKFKWRKDPQDK 254
||||||||||||||
Db 241 KDHKFKWRKDPQDK 254
Alignment with polypeptide encoded by nucleic acid of SEQ ID NO: 2 US-10-529-351A-506
Filing date in PALM: 2006-05-24
Sequence 506, US/10529351A
Publication No. US20070224201A1
GENERAL INFORMATION
APPLICANT: THOMAS D. WU
APPLICANT: ZEMIN ZHANG
TITLE OF INVENTION: COMPOSITIONS AND METHODS FOR THE DIAGNOSIS AND
TITLE OF INVENTION: TREATMENT OF TUMOR
FILE REFERENCE: P5101R1-US
CURRENT APPLICATION NUMBER: US/10/529,351A
CURRENT FILING DATE: 2005-03-25
PRIOR APPLICATION NUMBER: PCT/US03/28547
PRIOR FILING DATE: 2003-09-29
PRIOR APPLICATION NUMBER: US 60/414,971
PRIOR FILING DATE: 2002-10-02
NUMBER OF SEQ ID NOS: 6355
SEQ ID NO 506
LENGTH: 254
TYPE: PRT
ORGANISM: Homo sapiens
ALIGNMENT:
Length: 254
Score: 1359.00 Matches: 254
Percent Similarity: 100.0% Conservative: 0
Best Local Similarity: 100.0% Mismatches: 0
Query Match: 94.2% Indels: 0
Gaps: 0
US-17-295-010-2 (1-765) x US-10-409-608A-8 (1-254)
Qy 1 ATGTGGCAGCTGCTGCTGCCTACAGCTCTCCTGCTGCTGGTGTCCGCCGGCATGAGAACC 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 MetTrpGlnLeuLeuLeuProThrAlaLeuLeuLeuLeuValSerAlaGlyMetArgThr 20
Qy 61 GAGGATCTGCCTAAGGCCGTGGTGTTCCTGGAACCCCAGTGGTACAGAGTGCTGGAAAAG 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 21 GluAspLeuProLysAlaValValPheLeuGluProGlnTrpTyrArgValLeuGluLys 40
Qy 121 GACAGCGTGACCCTGAAGTGCCAGGGCGCCTACAGCCCCGAGGACAATAGCACCCAGTGG 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 41 AspSerValThrLeuLysCysGlnGlyAlaTyrSerProGluAspAsnSerThrGlnTrp 60
Qy 181 TTCCACAACGAGAGCCTGATCAGCAGCCAGGCCAGCAGCTACTTCATCGACGCCGCCACC 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 PheHisAsnGluSerLeuIleSerSerGlnAlaSerSerTyrPheIleAspAlaAlaThr 80
Qy 241 GTGGACGACAGCGGCGAGTATAGATGCCAGACCAACCTGAGCACCCTGAGCGACCCCGTG 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 81 ValAspAspSerGlyGluTyrArgCysGlnThrAsnLeuSerThrLeuSerAspProVal 100
Qy 301 CAGCTGGAAGTGCACATCGGATGGCTGCTGCTGCAGGCCCCCAGATGGGTGTTCAAAGAA 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 101 GlnLeuGluValHisIleGlyTrpLeuLeuLeuGlnAlaProArgTrpValPheLysGlu 120
Qy 361 GAGGACCCCATCCACCTGAGATGCCACTCTTGGAAGAACACCGCCCTGCACAAAGTGACC 420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 GluAspProIleHisLeuArgCysHisSerTrpLysAsnThrAlaLeuHisLysValThr 140
Qy 421 TACCTGCAGAACGGCAAGGGCAGAAAGTACTTCCACCACAACAGCGACTTCTACATCCCC 480
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 141 TyrLeuGlnAsnGlyLysGlyArgLysTyrPheHisHisAsnSerAspPheTyrIlePro 160
Qy 481 AAGGCCACCCTGAAGGACTCCGGCTCCTACTTCTGCAGAGGCCTCGTGGGCAGCAAGAAC 540
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 161 LysAlaThrLeuLysAspSerGlySerTyrPheCysArgGlyLeuValGlySerLysAsn 180
Qy 541 GTGTCCAGCGAGACAGTGAACATCACCATCACCCAGGGCCTGGCCGTGTCTACCATCAGC 600
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 ValSerSerGluThrValAsnIleThrIleThrGlnGlyLeuAlaValSerThrIleSer 200
Qy 601 AGCTTTTTCCCACCCGGCTACCAGGTGTCCTTCTGCCTCGTGATGGTGCTGCTGTTCGCC 660
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 201 SerPhePheProProGlyTyrGlnValSerPheCysLeuValMetValLeuLeuPheAla 220
Qy 661 GTGGACACCGGCCTGTACTTCAGCGTGAAAACAAACATCAGAAGCAGCACCCGGGACTGG 720
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 221 ValAspThrGlyLeuTyrPheSerValLysThrAsnIleArgSerSerThrArgAspTrp 240
Qy 721 AAGGACCACAAGTTCAAGTGGCGGAAGGACCCCCAGGACAAG 762
||||||||||||||||||||||||||||||||||||||||||
Db 241 LysAspHisLysPheLysTrpArgLysAspProGlnAspLys 254
Prosecution Insights