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 1-41 are pending.
Election/Restrictions
Applicant's election with traverse of Group I, claims 1-14, in the reply filed on 9-30-25 is acknowledged. The traversal is on the ground(s) that the restriction was improper because it wasn’t done using 37 CFR 1.475. This is not found persuasive because the claims STILL lack unity under 37 CFR 1.475.
As provided in 37 CFR 1.475(a), a national stage application shall relate to one invention only or to a group of inventions so linked as to form a single general inventive concept (“requirement of unity of invention”). Where a group of inventions is claimed in a national stage application, the requirement of unity of invention shall be fulfilled only when there is a technical relationship among those inventions involving one or more of the same or corresponding special technical features. The expression “special technical features” shall mean those technical features that define a contribution which each of the claimed inventions, considered as a whole, makes over the prior art.
The determination whether a group of inventions is so linked as to form a single general inventive concept shall be made without regard to whether the inventions are claimed in separate claims or as alternatives within a single claim. See 37 CFR 1.475(e).
When Claims Are Directed to Multiple Categories of Inventions:
As provided in 37 CFR 1.475 (b), a national stage application containing claims to different categories of invention will be considered to have unity of invention if the claims are drawn only to one of the following combinations of categories:
(1) A product and a process specially adapted for the manufacture of said product; or
(2) A product and a process of use of said product; or
(3) A product, a process specially adapted for the manufacture of the said product, and a use of the said product; or
(4) A process and an apparatus or means specifically designed for carrying out the said process; or
(5) A product, a process specially adapted for the manufacture of the said product, and an apparatus or means specifically designed for carrying out the said process.
Otherwise, unity of invention might not be present. See 37 CFR 1.475 (c).
Restriction is required under 35 U.S.C. 121 and 372.
This application contains the following inventions or groups of inventions which are not so linked as to form a single general inventive concept under PCT Rule 13.1.
In accordance with 37 CFR 1.499, applicant is required, in reply to this action, to elect a single invention to which the claims must be restricted.
Group I, claims 1-14, drawn to a method of treating a microbial infection in a subject by administering expanded natural killer (NK) cells.
Group II, claims 15-32, drawn to a method of generating expanded NK cells that have increased expression of KIR2KL2 using IL21, IL15, and/or 4-IBLL.
Group III, claims 33-41, drawn to a preclinical method of examining an NK cell adoptive immunotherapy for treating a 2019-nCoV infection using expanded NK cells administered to a canine infected with 2019-nCoV.
The groups of inventions listed above do not relate to a single general inventive concept under PCT Rule 13.1 because, under PCT Rule 13.2, they lack the same or corresponding special technical features for the following reasons:
Groups I-II lack unity of invention because the groups do not share the same or corresponding technical feature. The method of treating microbial infection in Group I does not require expanding NK cells in IL21, IL15, and/or 4-IBBL as required in Group II or administering NK cells to a canine infected with 2019-nCoV as required in Group III. The method of expanding NK cells in IL21, IL15, and/or 4-IBBL as required in Group II does not require administering NK cells to a canine infected with 2019-nCoV as required in Group III.
Groups I-III also lack unity of invention because even though the inventions of these groups require the technical feature of expanded NK cells; however, this technical feature is not a special technical feature as it does not make a contribution over the prior art in view of Decot (Exp. Hematol., 2010, Vol. 38, pg 1-12) who taught expanding NK cells in the presence of IL15 such that increased level of KIR2KL2 is observed (pg 1, abstract).
The requirement is still deemed proper and is therefore made FINAL because the result is the same.
Claims 15-41 have been withdrawn.
Claims 1-14 are under consideration.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—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 or joint inventor of carrying out the invention.
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.
Claim 6 is 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.
Claim 6 encompasses administering NK cells that have been expanded in vivo to a subject with a microbial infection. This does not make sense because NK cells cannot be expanded in vivo and administered to a subject at the same time. The specification does not contemplate expanding NK cells in vivo using any means followed by isolating the NK cells and administration to a subject with a microbial infection. Accordingly, the concept lacks written description.
Indefiniteness
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 1-14 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.
It is unclear whether the term “expanded” is an attempt to invoke product-by-process language for the NK cells used in the method of treatment or whether applicants are attempting to set forth a clear, positive step of “expanding” NK cells prior to administering them to the subject. Burying a product-by-process in the method of treatment in claim 1 without clearly setting forth the active step of “expanding” makes the claim unclear because the limitation does not distinguish the structure/function of “expanded” NK cells from any well-known NK cells.
Claim 2 is indefinite because NK cells cannot be “expanded” and “nonexpanded” at the same time. Therefore, the limitation of “nonexpanded” NK cells in claim 2 cannot further limit the “expanded” NK cells in claim 1. Claim 2 is also unclear because it is further limiting the product-by-process language for reasons set forth above. Claim 2 fails to clearly set forth a positive step of contacting NK cells with IL21, IL15 or 4BBL such that the number of NK cells increases followed by administering the NK cells to the subject. Finally, claim 2 is indefinite because the metes and bounds of when an NK cell is ”nonactivated” cannot be determined. The structures/functions that define when an NK cell is “nonactivated are not taught in the specification or the art at the time of filing. It is especially confusing when applicants appear to be saying the NK cells have been “expanded” and are, therefore, “activated”. NK cells cannot be expanding and “nonactivated” at the same time as claimed.
It is unclear how the term “soluble” further limits IL21, IL15 or 4BBL in claim 3 because any IL21, IL15 or 4BBL in a solution or culture medium is “soluble”, i.e. dissolved in solution.
The term 41BBL in claims 3 and 4 lacks antecedent basis.
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.
Claims 5-14 are objected to under 37 CFR 1.75(c) as being in improper form because they are multiple dependent claims. See MPEP § 608.01(n).
Claim 5 and 6 are indefinite because NK cells cannot be “expanded” and “nonexpanded” at the same time. Therefore, the limitation of “nonexpanded” NK cells in claim 5 and 6 cannot further limit the “expanded” NK cells in claim 2-4. Claims 5 and 6 are also unclear because they further limit the product-by-process language for reasons set forth above. Claim 5 and 6 fail to clearly set forth a positive step of expanding NK cells in vivo or in vitro followed by administering the NK cells to the subject.
Claims 5 and 6 are indefinite for reasons set forth above in claim 2 regarding the term “nonactivated”.
Claim 6 is indefinite because NK cells cannot be expanded in vivo and administered to a subject at the same time. Therefore, “expansion of the [ ] NK cells” cannot be in vivo as required in claim 6.
The metes and bounds of when a vesicle, exosome or feeder cell is “derived from PBMC, RPMI8866, NK92, NK92MI…” 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.
Claim 8 is indefinite because NK cells cannot be “expanded” and “nonexpanded” at the same time for reasons set forth above.
Claim 8 is indefinite for reasons set forth above in claim 2 regarding the term “nonactivated”.
The Markush Group in claim 9 is improper because the list is not limited to “NK cell receptors”. For example 41BB is found on T-cells and is not an NK cell receptor. CD226 is found on NK cells, T-cells and platelets and is not specific to NK cells. Therefore, the use of “NK cell receptors” to describe the Markush group is improper.
Claim Rejections - 35 USC § 102
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 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 1-14 are rejected under 35 U.S.C. 102a1 as being anticipated by Copik (20200061115).
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 “expanded” as required in claim 1 because they are cultured first. This is equivalent to claim 1.
In an alternative interpretation, the term “expanded” appears to be an attempt to invoke product-by-process language for the NK cells used in the method of treatment. However, claim 1 lacks any active step of culturing and expanding NK cells prior to administering them to the subject. Burying a product-by-process in the method of treatment in claim 1 without clearly setting forth the active step of “expanding” does not bear patentable weight because it does not distinguish the structure/function of “expanded” NK cells from any well-known NK cells. Therefore, the NK cells placed in culture and contacted with PM21 particles and/or FC21 and optionally stimulated with IL2, IL12, IL18, IL21, 4BBL described by Copik are “expanded” because they have the same structure/function as those described by applicants.
IL15, IL21, or 4BBL can be added in vitro (para 3, 26, 30-32, 36, 37, 39, 44-47, 67, 73, 88, 95, 97) which is equivalent to claim 2.
The IL15 or IL21 inherently MUST be soluble as required in claim 3 because it is used in culture.
Claim 4 requires the IL15 or IL21 are “expressed 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, FC21 cells described by Copik are feeder cells expressing IL21 (para 32) as required in claim 4.
The NK cells are in culture which is “ex vivo” as required in claim 5.
The NK cells cannot be “expanded” in vivo as required in claim 6; therefore, claim 6 has been included because it is indefinite. It has also been included because the claims never clearly set forth an active step of “expanding” NK, so “the expansion” lacks antecedent basis.
The FC21 cells used by Copik are equivalent to PBMCs, RPMI8866, NK92, NK92MI, NK-YTS, NK, NKL, KIL, KIL C.2, NK-YS, HFWT, K562 or EBV-LCL cells as required in claim 7 because the names listed are meaningless and do not have any structures/functions associated with them. The FC21 cells of Copik could easily be called RPMI8866, NK92, NK92MI, NK-YTS, NK, NKL, KIL, KIL C.2, NK-YS, HFWT, K562 or EBV-LCL cells which makes them equivalent to those in claim 7. Copik taught K562 cells in para 72 et al and PBMC, RPMI8866, K562 SKOV3 and EBV-LCL cells in para 39.
The NK cells of Copik 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 FC21 cells of Copik 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 express CD112 (para 30, 46, 47), 2B4 (30, 32, 46, 47) 41BB (67), NKp46 (72, 86), NKG2D (72, 86), KIR2DAPC (72), NKp44 (72, 86) as required in claim 9.
The NK cells of Copik 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 39, 48, 75, 79, 91, 94) or haploidentical (para 48) as required in claim 11.
The infection is viral (para 4, 6) as required in claim 12.
The virus may be herpesvirus (para 42) as required in claim 13.
Claim 14 has been included because it further limits the coronavirus of claim 13 without limiting the claim to treating a subject infected with a coronavirus. Claim 14 still encompasses treating herpesvirus which is taught by Copik. This is all that is needed to meet the breadth of claim 14.
Claims 1-14 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 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 first. This is equivalent to claim 1.
In an alternative interpretation, the term “expanded” appears to be an attempt to invoke product-by-process language for the NK cells used in the method of treatment. However, claim 1 lacks any active step of culturing and expanding NK cells prior to administering them to the subject. Burying a product-by-process in the method of treatment in claim 1 without clearly setting forth the active step of “expanding” does not bear patentable weight because it does not distinguish the structure/function of “expanded” NK cells from any well-known NK cells. Therefore, the NK cells placed in culture and contacted with IL2, IL12, IL18, IL21, 4BBL described by Ji are “expanded” because they have the same structure/function as those described by applicants.
IL15, IL21, or 4BBL can be added in vitro (para 15, 61, 73, 75, claims 6, 32, 52) which is equivalent to claim 2.
The IL15 or IL21 inherently MUST be soluble as required in claim 3 because it is used in culture.
Claim 4 requires the IL15 or IL21 are “expressed 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 NK cells are in culture which is “ex vivo” as required in claim 5.
The NK cells cannot be “expanded” in vivo as required in claim 6; therefore, claim 6 has been included because it is indefinite. It has also been included because the claims never clearly set forth an active step of “expanding” NK, so “the expansion” lacks antecedent basis.
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 express NKp46 (39, 61), NKG2D (7, 56), NKp44 (56), NKp30 (61) as required in claim 9.
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.
The infection is viral as required in claim 12.
The virus may be coronavirus (title; claims) as required in claim 13.
Ji taught the coronavirus was SARS-CoV or MERS (para 4, 6; claims 9, 35, 55).
Conclusion
No claim is allowed.
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Michael C. Wilson
/MICHAEL C WILSON/
Primary Examiner, Art Unit 1638