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 .
Claims 2, 3, 5, 6, 9, 12, 13, 17, 19, 21, 23, 26-32, 36, 37, 39 have been canceled. Claims 1, 4, 7, 8, 10, 11, 14-16, 18, 20, 22, 24, 25, 33-35, 38, 40, 41 remain pending.
Election/Restrictions
Applicant's elected Group I, claims 1-14, with traverse in the reply filed on 9-30-25.
Claims 15, 16, 18, 20, 22, 24, 25, 33, 38, 40, 41 remain withdrawn.
Claims 1, 4, 7, 8, 10, 11, 14 remain under consideration.
Applicant's arguments filed 4-28-26 have been fully considered but they are not persuasive.
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claim objections
The preamble in claims 4, 7, 8, 10, 11, 14 should be the same as claim 1, i.e. “microbial infection” should be ---coronavirus infection---.
The term “NK” in claim 1 should be spelled out before being abbreviated.
Adding letters or numbers to the steps in claim 1 would help clarify the claims and aid in discussion of the claims.
Claim 1 is missing any therapeutic effect in the body of the claim. The final step is missing any functional language, i.e. administering the NK such that….
Claim 1 is missing a route of administration for the NK cells.
Claim 1 encompasses treating coronavirus infection in any plant, invertebrate, insect, or other “subject”; however, the specification and art are limited to treating humans.
The “increased expression” of KIR2DL2, CD226, 2B4, CD11a, OX40, 41BB, CD223, or ICOS “relative to a control” in claim 1 fails to capture the proper control. Expression of the proteins must be greater after “culturing” as compared to before.
Claim 1 can be simplified by saying ---A method of treating coronavirus infection, the method comprising: a) culturing [human] natural killer (NK) cells in the presence of IL21, IL15, or 41BBL such that expanded NK cells are obtained, wherein the expanded NK cells express an increased amount of KIR2DL2, CD226, 2B4, CD11a, OX40, 41BB, CD223, or ICOS as compared to prior to culturing;
administering the expanded NK cells to a [human that has a coronavirus infection intravenously such that symptoms of the coronavirus infection are ameliorated]---.
Claim 4 can be written more clearly as ---wherein the IL21, IL15, or 41BBL are bound to the surface of a vesicle, exosome, liposome, or feeder cell---. However, this does not make sense. IL21, IL15, 41BBL must be secreted by the vesicle, exosome, liposome, or feeder cell; they are not “bound” as claimed.
Claim 7 can be written more clearly as ---wherein the vesicle, exosome, liposome, or feeder cell is obtained from a peripheral blood mononuclear cell (PBMC) or an RPMI8866, NK-92, NK92-MI, NK-YTS, NK, NKL, KIL, KILC2, NK3.3, NK-YS, HFWT, K562, or EBV-LCL cell---. It is assumed the metes and bounds of RPMI8866, NK-92, NK92-MI, and K562 were well-known because they are established cell lines, and NK cells were well-known as natural killer cells, but the metes and bounds of NK-YTS, NKL, KIL, KILC2, NK3.3, NK-YS, HFWT, and EBV-LCL cannot be determined.
Claim 8 can be written more clearly as ---wherein the NK cell is a primary NK cell, a CAR-NK cell, a memory-like NK cell, or an NK cell line---. However, an “NK cell line” is a plurality of cells, but “the NK cell” is singular – this does not make grammatical sense.
Claim 10 can be written more clearly as --- wherein the expanded NK cells express an increased amount of granzyme B, tumor necrosis factor α (TNFα), interferon γ (INFγ), or perforin as compared to prior to culturing---.
Claim 11 can be written more clearly as ---wherein the expanded NK cells are autologous, haploidentical, or allogeneic---.
Claim Rejections - 35 USC § 112
Written Description
The rejection of claim 6 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, written description, has been withdrawn because the claim has been canceled.
Claim 1, 4, 7, 8, 10, 11, 14 as newly amended are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
The specification lacks written description for treating any coronavirus by i) contacting NK cell with IL21, IL15 or 41BBL such that NK cells with increased expression of KIR2DL2, CD226, 2B4, CD11a, OX40, 41BB, CD223 or ICOS as compared to a control are obtained, and ii) administering the NK cell obtained in step i) to any subject as broadly encompassed by claim 1.
The claim encompasses culturing any species of NK cells in the presence of IL21, IL15 or 41BBL such that NK cells with increased expression of KIR2DL2, CD226, 2B4, CD11a, OX40, 41BB, CD223 or ICOS as compared to any control are obtained. The claim encompasses administering the NK cells obtained to any species of subject including plants, bacteria, viruses, invertebrates, fish, amphibians, reptiles, birds or mammals. The subject may be infected with coronavirus or not.
The specification is limited to contacting human NK cell with IL21, IL15 and 41BBL such that NK cells with increased expression of KIR2DL2, CD226, 2B4, CD11a, OX40, 41BB, CD223 and ICOS as compared to human NK cells not treated with the IL21, IL15 or 41BBL are obtained. The specification does not correlate human NK cells to any plant, bacteria, virus, invertebrate, fish, amphibians, reptiles, bird or non-human mammal cells. The specification is limited to administering the human NK cell obtained in step i) to a human infected with coronavirus intravenously. The specification does not correlate treating humans to treating any plants, bacteria, viruses, invertebrates, fish, amphibians, reptiles, birds or non-human mammals. The specification does not correlate administering the NK cells intravenous to administering the NK cells via intramuscular, intradermal, intranasal, intraocular,… administration. The specification does not correlate NK cells treated with IL21, IL15 and 41BBL that expressed increased amounts of KIR2DL2, CD226, 2B4, CD11a, OX40, 41BB, CD223 and ICOS to using IL21, IL15 or 41BBL as broadly claimed or to obtaining NK cells that express the one, two, three,… of the proteins listed without all of them being increased. The claim encompasses obtaining no effect after administering the NK cells because it does not have any functional effect after administering the NK cells, i.e. ---such that symptoms of coronavirus infection are ameliorated---. The specification does not provide any use for administering the NK cells without a therapeutic effect.
Indefiniteness
Claims 4, 7 remain 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.
The metes and bound of an “engineered” plasma membrane vesicle, exosome, liposome, or feeder cell in claim 4 cannot be determined. The claim requires the items are “engineered to express membrane bound” IL21, IL15, or 4BBL; however, the claim does not require the plasma membrane vesicle, exosome, liposome, or feeder cell is genetically modified with a nucleic acid sequence encoding IL21, IL15, or 4BBL. More importantly vesicles, exosomes and liposomes are not genetically modified, so it’s impossible to determine what you mean. Next, the metes and bounds of a plasma membrane vesicle with a membrane bound IL21, IL15, or 4BBL cannot be determined. Nor can metes and bounds of an exosome or liposome with a membrane bound IL21, IL15, or 4BBL be determined. Accordingly, those of skill would not be able to determine when they were infringing on the claim.
The metes and bounds of when a vesicle, exosome or feeder cell is “derived from PBMC, RPMI8866, NK92, NK92MI…” cannot be determined as required in claim 7. The structures/functions associated with “PBMC, RPMI8866, NK92, NK92MI…” cannot be determined, so the metes and bounds of the starting material are unclear. And it cannot be determined when a vesicle, exosome or feeder cell has been “derived” because it is unclear what structures/functions must remain of the “PBMC, RPMI8866, NK92, NK92MI…” must remain. Therefore, the metes and bounds of the final structure of when a vesicle, exosome or feeder cell has been “derived” from “PBMC, RPMI8866, NK92, NK92MI…” cannot be determined.
Response to arguments
Applicants argue the amendment overcomes the rejection. Applicants’ argument is not persuasive for reasons set forth above.
Claim Rejections - 35 USC § 102
The rejection of claims 1, 4, 7, 8, 10, 11, 14 under 35 U.S.C. 102a1 as being anticipated by Copik (20200061115) has been withdrawn. Copik taught culturing NK cells and administering them to a subject with a viral infection (pg 1, para 4, 6; Fig. 1). The NK cells are placed in culture and contacted with PM21 particles and/or FC21 and optionally stimulated with IL2, IL12, IL18, IL21, 4BBL (claim 8; para 3, 26, 30-32, 36, 37, 39, 44-47, 67, 73, 88, 95, 97). The NK cells are “obtained” and “expanded” as required in claim 1 because they are obtained and then cultured. Copik did not teach the virus was coronavirus as required in claim 1 as newly amended.
Claims 1, 4, 7, 8, 10, 11, 14 as newly amended are rejected under 35 U.S.C. 102a1 as being anticipated by Ji (20230071405).
The effective filing date of ‘405 is 1-28-20, the filing date of provisional application 62/966934, which is prior to applicants effective filing date of 3-11-20.
Ji taught culturing/expanding NK cells and administering them to a subject with a coronaviral infection (title, examples, claims). The NK cells are placed in culture and contacted with IL2, IL12, IL18, IL21, 41BBL (para 15, 61, 73, 75, claims 6, 32, 52). The NK cells are “expanded” as required in claim 1 because they are cultured in the presence of growth factors. The cells inherently MUST exhibit an increased amount of KIR2DL2, CD226, 2B4, CD11a, OX40, 41BB, CD223, or ICOS as compared to prior to culturing as encompassed by claim 1 because they were made by the exact same method claimed and because they were made by a method described by applicants as being part of the invention, i.e. culturing/expanding NK cells in IL21 and/or 41BBL. This is equivalent to claim 1.
Claim 4 requires the IL15 or IL21 are “on the surface of an engineered membrane vesicle, engineered exosome, engineered liposome, or engineered feeder cell”; however, this is a product-by-process limitation further limiting the IL15 or IL21 without clearly setting forth an active step of culturing NK cells in the presence of an “engineered membrane vesicle, engineered exosome, engineered liposome, or engineered feeder cell”. Regardless, K562 cells described by Ji are feeder cells (para 29, 85) as required in claim 4.
The K562 cells used by Ji are equivalent to K562 as required in claim 7.
The NK cells of Ji are a primary NK cell, CAR-NK cell, memory-like NK, or NK cell line as required in claim 8 because the metes and bounds of the terms cannot be determined and do not have any structures/functions associated with them. The K562 cells of Ji could easily be called primary NK cells, CAR-NK cells, memory-like NK cells, or an NK cell line which makes them equivalent to those in claim 8.
The NK cells of Ji inherently MUST express increased granzyme B, TNFα, IFNγ or perforin as required in claim 10 because they were made using a method described by applicants as being part of the invention.
The NK cells are autologous or allogeneic (para 8, 10, 11, 13, 14, 37, 38, 41, 58, 62) as required in claim 11.
Ji taught the coronavirus was SARS-CoV or MERS as required in claim 14 (para 4, 6; claims 9, 35, 55).
Response to arguments
Applicants argue Ji did not teach the expression pattern claimed. Applicants’ argument is not persuasive. The cells inherently MUST exhibit an increased amount of KIR2DL2, CD226, 2B4, CD11a, OX40, 41BB, CD223, or ICOS as compared to prior to culturing as encompassed by claim 1 because they were made by the exact same method claimed and because they were made by a method described by applicants as being part of the invention, i.e. culturing/expanding NK cells in IL21 and/or 41BBL. This is equivalent to claim 1.
Conclusion
No claim is allowed. Applicant's 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 nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Inquiry concerning this communication or earlier communications from the examiner should be directed to Michael C. Wilson who can normally be reached at the office on Monday through Friday from 9:30 am to 6:00 pm at 571-272-0738.
Patent applicants with problems or questions regarding electronic images that can be viewed in the Patent Application Information Retrieval system (PAIR) can now contact the USPTO’s Patent Electronic Business Center (Patent EBC) for assistance. Representatives are available to answer your questions daily from 6 am to midnight (EST). The toll free number is (866) 217-9197. When calling please have your application serial or patent number, the type of document you are having an image problem with, the number of pages and the specific nature of the problem. The Patent Electronic Business Center will notify applicants of the resolution of the problem within 5-7 business days. Applicants can also check PAIR to confirm that the problem has been corrected. The USPTO’s Patent Electronic Business Center is a complete service center supporting all patent business on the Internet. The USPTO’s PAIR system provides Internet-based access to patent application status and history information. It also enables applicants to view the scanned images of their own application file folder(s) as well as general patent information available to the public.
For all other customer support, please call the USPTO Call Center (UCC) at 800-786-9199.
If attempts to reach the examiner are unsuccessful, the examiner's supervisor, Tracy Vivlemore, can be reached on 571-272-2914.
The official fax number for this Group is (571) 273-8300.
Michael C. Wilson
/MICHAEL C WILSON/
Primary Examiner, Art Unit 1638
Prosecution Insights