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. Status of Claims Claims 1-55 are cancelled. No restriction is being imposed in this case. Claims 56-84 are pending and under examination. Effective Filing Date Applicant's claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) and 365(c) are acknowledged. No foreign priority claims are made. Based on the information given by Applicant and an inspection of the prior applications, the examiner has concluded that the subject matter defined in the instant claims is supported by the disclosure in PCT/EP2022/057824 and provisional application serial no. 63/166,374 . The effective filing date of claims 56-84 is 03/26/2021. Claim Objections Claims 74 and 75 are objected to because of the following informalities: these claims recite a method of treating “an infectious in an individual” and this is interpreted for examination purposes as “an infection in an individual , ” which corresponds to the language of the specification. Appropriate correction is required. Claim 71 is objected to because of the following informalities: the claim recites “which expresses at the polypeptide chains” and this is interpreted for examination purposes as “expresses the polypeptide chains,” which corresponds to the language of the specification. Appropriate correction is required. 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. Claims 56 -84 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. Claim 56 recites an antigen binding domain (ABD) that binds to an antigen of interest. The specification, however, fails to describe the species of antigen that are encompassed by the claim. T here is no evidence in the specification to support that the inventors had possession of the genus contemplated. The written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, reduction to drawings, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus. See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406. See MPEP 2163. In the instant case, the specification discloses only CD20, EGFR, ROR1, and KIR3DL2 . The disclosure fails to describe a representative number of species within the genus claimed. Therefore, the specification fails to reasonably convey to one skilled in the relevant art that the inventor, at the time the application was filed, had possession of the claimed genus. Furthermore, claims 57 -84 require the ABD at issue, and are thus also rejected. Additionally, claims 82-84 recite a method of preventing cancer. The specification, however, demonstrates eliminating tumor cell s and treatment of established tumors, but does not provide evidence or description of preventing cancer. Furthermore , the specification fails to describe the species of cancer that are encompassed by the claim. T here is no evidence in the specification to support that the inventors had possession of the genus contemplated. The written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, reduction to drawings, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus. See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406. See MPEP 2163. In the instant case, the specification discloses only B-cell lymphoma . The disclosure fails to describe a representative number of species within the genus claimed. Therefore, the specification fails to reasonably convey to one skilled in the relevant art that the inventor, at the time the application was filed, had possession of the claimed genus. Therefore, claims 56-84 are rejected under 35 U.S.C. 112(a) for lack of written description. 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. Claim s 56 -84 are rejected under 35 U.S.C. 103 as being unpatentable over Gauthier ( WO2019101695A1 ). Claims 56-69 are drawn to a multispecific protein and various structural variations, claim 70 is drawn to a pharmaceutical composition comprising the protein, claims 71-73 are drawn to cell s expressing the protein and methods of making said cells, claim 81 is drawn to a method of making the protein, and claims 74-80 and 82-84 are drawn to methods of use for the protein and cell compositions. Gauthier discloses multispecific protein s comprising multiple polypeptide chains , including heterodimeric and he te rotrimeric formats (instant claim 67) , that bind an antigen of interest expressed on a target cell and one or more activating NK cell receptors, to include NKp46 and CD16A , and further comprise an Fc domain capable of binding FcRn . Gauthier teaches that such constructs potentiate NK cell mediated cytotoxicity towards target cells expressing the antigen of interest [see Summary of the Invention] (instant claim 56) . Gauthier further teaches that each target antigen and activating receptor may be engaged monovalently, expressly stat ing that engaging antigens monovalently can improve potency [see p. 71, line 10 ] (instant claim 57). Gauthier discloses that antigen binding domains ( ABD ) comprise VH and VL regions containing three CDRs [see p. 6, line 21 ] (instant claim 65) , and that variable regions , binding domains, and/or Fc domains may be connected via peptide linkers [see p. 41, line 19 ] . L inkers may comprise between 2 and 50 residues and may include sequences such as RTVA [see p. 41 , par . 4-6 ] (instant claims 61-63). Gauthier additionally teaches modular fusion of domains at N- and C-termini of polypeptide chains , incorporation of additional binding domains as needed [see p. 25, par . 4-6 ] , and numerous alternative domain arrangements with the disclosure , all demonstrating flexibility in domain ordering and linkage. These teachings provide evidence that rearrangement of domains within the disclosed formats would have been a matter of routine design choice and optimization, motivated by considerations such as preserving binding affinity, improving folding efficiency, reducing misfolding, and optimizing receptor accessibility (instant claims 64 and 66). As discussed above, Gauthier discloses simultaneous binding of multiple NK cell receptors and target antigens. Given the disclosed flexible linkers and modular domain arrangements designed to permit concurrent receptor engagement, the ability of the construct to adopt a membrane planar binding conformation suitable for binding NKp46 and other NK cell surface receptors represents an inherent structural capability of the disclosed multispecific proteins (instant claim 60). Gauthier discloses that the protein may comprise a pharmaceutically acceptable carrier [see claim 40] (instant claim 70) or be expressed in a recombinant cell [see claim 39] (instant claim 71). Gauthier discloses in vitro incubation of NK cells with multispecific proteins in the presence of target cells to enhance NK cell cytotoxicity, resulting in activated NK cell compositions [see p. 52, par . 3 ] (instant claims 72 and 73). Gauthier further discloses administration of the multispecific proteins to patients with cancer, which potentiates NK cell activity and cytotoxicity [see p.56, line 25] (instant claims 74 and 76). Of note, instant claim 76 requires the immune cells be NKp46 positive and CD16 positive and/or NKp46 positive CD16 negative, which encompasses the totality of NK cells. Further, a ctivation of NK cells through engagement of activating receptors, as taught by Gauthier, inherently enhances NK cell proliferation, survival, recruitment, and tumor infiltration . Similarly, engagement of NK cells at the tumor site inherently promotes accumulation of NK cells , which are NKp46 expressing cells, within the tumor microenvironment (instant claims 77 and 78). Further , selectively activating NK cells using the disclosed multispecific protein rather than broad immune stimulation would inherently potentiate NK cells over CD25 expressing lymphocytes (instant claim 79). Finally, Gauthier discloses a method of making a heteromultimeric protein comprising co-expression of the polypeptide chains and purification via Fc-binding supports , such as Protein A, corresponding to the claimed methods of the instant application [see claim 44] (instant claim 81). Gauthier does not expressly disclose a multispecific construct comprising both an NKp46-binding moiety and a cytokine receptor binding moiety within the same protein. Gauthier also does not expressly disclose administration of a population of cells or a diagnostic step prior to an administration step , such as detecting tumor antigen expression, NK cell levels, or CD16 status. However, Gauthier explicitly teaches that cytokine receptors are suitable for activating NK cell receptors [see p. 20, par. 4] . Gauthier further teaches that additional ABDs can be positioned at the N- or C-termini of the polypeptide chains and that such domains can be linked via CH1/CK domains and/or peptide linkers to Fc domain s [see p. 36, par. 2] . Given cytokine receptors and NKp46 receptors share the functional role of activating NK cell cytotoxicity, and in view of Gauthier’s teachings of modular incorporation of multiple activating receptor binding domains, it would have been obvious to incorporate an additional NK activating moiety, such as cytokine receptor binding domain, into a construct already comprising an NKp46 binding domain, to further enhance NK cell activation and cytotoxicity. Furthermore, it would have been obvious to attach the cytokine receptor binding domain via a peptide linker , as Gauthier teaches that link er s can be placed as needed and discloses routine use of linkers between variable domains and Fc domains to preserve folding and binding function [see p. 25, par. 3] (instant claim 58). The specific selection of linker length within the ranges taught by Gauthier above represents routine optimization (instant claims 61-63). Regarding the specific constructions of the multispecific protein, s electing a configuration comprising only a single antigen-binding domain per target antigen and a single Fc domain dimer likewise represents an obvious design choice given the disclosed multispecific formats , motivated by predictable effects on size, manufacturability, and receptor engage men t efficiency (instant claim 57). Similarly , Gauthier discloses heterodimeric and heterotrimeric protein formats in which VH and VL domains may be split across chains that associate to form functional ABDs, as well as single chains comprising scFV arrangements [see p. 17, par. 3] . Given Gauthier’s disclos ure of modular domain assembly, CH1/CL pairing, and flexible linker placement, constructing either a multispecific protein with an NKp46 ABD and a cytokine receptor binding domain comprising two chains (instant claim 68) or a multispecific protein consisting of a single polypeptide chain comprising an NKp46 A B D and a cytokine receptor binding domain (instant claim 69) represent s routine design choice of the disclosed modular protein . Regarding claim 59, for the purposes of examination, “in series” is understood in the art to describe a topological limitation and not a sequence order, requiring only that the components be arranged linearly along the polypeptide chain. As discussed above, Gauthier repeatedly describes linear domain arrangements in which function domains are fused sequentially along a single polypeptide chain. Such linear fusions necessarily position the domains in series relative to the N- and C- termini. Given this, arranging an NKp46-binding moiety, an Fc domain, and a cytokine receptor binding moiety sequentially along a polypeptide chain represents an obvious and predictable variation of the disclosed protein. Regarding administration , although Gauthier does not expressly teach administering the pre-activated NK cell composition to a patient, transfer of immune effector cells was well established in the art, and it would have been obvious and routine to administer such activated NK cells to achieve the same therapeutic objective as direct protein administration (instant claim 75). Furthermore, incorporat ing a cytokine receptor binding moiety into a multispecific construct to be administered would be obvious as it would predictably isolate cytokine activity to NK cells and/or tumor sites, thereby delivering cytokine stimulation in a targeted manner with reduced cytotoxicity (instant claim 80) . Finally, a lthough Gauthier does not specifically disclose a detecting step in the administration of the multispecific protein, it would have been obvious to detect the presence of the target antigen in a patient sample prior to administration, as detection of tumor antigens to g ui de targeted therapies was routine in the art at the time (instant claim 82). Similarly, detecting NK cells or DC16 expression in a tumor sample from a patient to determine suitability for treatment was equally routine and predictable in immunotherapy (instant s claim 83 and 84 ). Therefore, claims 56-84 are rejected under 35 U.S.C. 103 . Conclusion No claims are allowed. Any inquiry concerning this communication or earlier communications from the examiner should be directed to FILLIN "Examiner name" \* MERGEFORMAT Tirone D Johnson whose telephone number is FILLIN "Phone number" \* MERGEFORMAT (571)272-1256 . The examiner can normally be reached FILLIN "Work Schedule?" \* MERGEFORMAT M-F, 9-5 ET . Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice. If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, FILLIN "SPE Name?" \* MERGEFORMAT Jeffrey Stucker can be reached at FILLIN "SPE Phone?" \* MERGEFORMAT (571)272-0911 . The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300. 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