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. 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 46- 52, 54-57, 59- 65 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 rejected claims cover an isolated recombinant cell modified to overexpress and/or contain elevated levels of a SLP-76 polypeptide . To satisfy the written-description requirement, the specification must describe every element of the claimed invention in sufficient detail so that one of ordinary skill in the art would recognize that the inventor possessed the claimed invention at the time of filing. Vas-Cat h, 935 F.3d at 1563; see also Lockwood v. American Airlines, Inc ., 107 F.3d 1565, 1572 (Fed. Cir. 1997) (patent specification must describe an invention and do so in sufficient detail that one skilled in the art can clearly conclude that “the inventor invented the claimed invention”); In re Gosteli , 872 F.2d 1008, 1012 (Fed. Cir. 1989) (“the description must clearly allow persons of ordinary skill in the art to recognize that [the inventor] invented what is claimed”). the following applies to the recited genus of SLP-76 polypeptide s and CART cells that contain them : Ariad Pharmaceuticals Inc. v. Eli Lilly & Co., 94 USPQ2d 1161 (Fed. Cir. 2010) states that “...a generic claim may define the boundaries of a vast genus of chemical compounds...the question may still remain whether the specification, including the original claim language, demonstrates that the applicant invented species sufficient to support a claim to a genus”. See page 1171. 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 also Fujikawa v. Wattanasin , 93 F.3d 1559, 1571, 39 USPQ2d 1895, 1905 (Fed. Cir. 1996) (a “laundry list” disclosure of every possible moiety does not constitute a written description of every species in a genus because it would not “reasonably lead” those skilled in the art to any particular species. Amgen, Inc. v. Chugai Pharmaceutical Co., Ltd., 927 F.2d 1200, 1206, 18 USPQ2d 1016, 1021 (Fed. Cir. 1991) states that “it is well established in our law that conception of a chemical compound requires that the inventor be able to define it so as to distinguish it from other materials, and to describe how to obtain it”. A description of a genus may be achieved by means of a recitation of a representative number of species falling within the scope of the genus or structural features common to the members of the genus, which features constitute a substantial portion of the genus, so that one of skill in the art can “visualize or recognize” the members of the genus (Emphasis added). Regents of the University of California v. Eli Lilly & Co., 119 F3d 1559, 1569, 43 USPQ2d 1398, 1406 (Fed. Cir. 1997). A “representative number of species” means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus . The disclosure of only one species encompassed within a genus adequately describes a claim directed to that genus only if the disclosure “indicates that the patentee has invented species sufficient to constitute the gen[us].” See Enzo Biochem , 323 F.3d at 966, 63 USPQ2d at 1615; Noelle v. Lederman, 355 F.3d 1343, 1350, 69 USPQ2d 1508, 1514 (Fed. Cir. 2004) (Fed. Cir. 2004)( “[A] patentee of a biotechnological invention cannot necessarily claim a genus after only describing a limited number of species because there may be unpredictability in the results obtained from species other than those specifically enumerated.”). “A patentee will not be deemed to have invented species sufficient to constitute the genus by virtue of having disclosed a single species when ... the evidence indicates ordinary artisans could not predict the operability in the invention of any species other than the one disclosed.” In re Curtis, 354 F.3d 1347, 1358, 69 USPQ2d 1274, 1282 (Fed. Cir. 2004). In Regents of the University of California v. Eli Lilly (43 USPQ2d 1398-1412), the court held that a generic statement which defines a genus of nucleic acids by only their functional activity does not provide an adequate written description of the genus . The court indicated that, while applicants are not required to disclose every species encompassed by a genus, the description of the genus is achieved by the recitation of a representative number of species falling within the scope of the claimed genus. At section B( i ), the court states, "An adequate written description of a DNA ... requires a precise definition, such as by structure, formula, chemical name, or physical properties, not a mere wish or plan for obtaining the claimed chemical invention." Courts have stated that “[ i ]n claims involving [non-genetic] chemical materials, generic formulae usually indicate with specificity what the generic claims encompas s. One skilled in the art can distinguish such a formula from others and can identify many of the species that the claims encompass. Accordingly, such a formula is normally an adequate description of the claimed genus.” Regents of the University of California v. Eli Lilly & Co ., 119 F.3d 1559, 1568 (Fed. Cir. 1997), cert. denie d, 523 U.S. 1089 (1998). (emphasis added). There is no such specificity here, nor could one skilled in the art identify any particular SLP-76 polypeptides . Specifically, Applicant fails to disclose any other SLP-76 polypeptides , besides those covered by the SEQ ID NO’s in the specification and claims, and in relation to the above, these disclosed species or subgenre do not represent the substantial variety covered by the genus of SLP-76 polypeptides . With regard to the functional definition of SLP-76 polypeptide , t he specification does not clearly allow persons of ordinary skill in the art to recognize that he or she invented what is clai med (see Vas-Cath at page 1116) because t he specification contains almost no information by which a person of ordinary skill in the art would understand that the inventors possessed the all of the recited compounds. At best, it simply indicates that one should test an inordinate number of peptides to see if the peptides can perform the required function . See In re ’318 Patent Infringement Litigation, 583 F.3d 1317, 1327 (Fed. Cir. 2009) (“[A]t the end of the day, the specification, even read in light of the knowledge of those skilled in the art, does no more than state a hypothesis and propose testing to determine the accuracy of that hypothesis. That is not sufficient.”). In this connection, the specification contains no generic structural characteristics of SLP-76 polypeptides . The Examiner acknowledges that a working example or exemplified embodiment is not necessarily a requirement for description. However, where a generic claim term is present in a claim, as in the present application, and defined only by functional characteristics, the specification must convey enough information, e.g., via sufficient representative examples, to indicate invention of species sufficient to constitute the genus. Enzo Biochem , Inc. v. Gen-Probe Inc., 323 F.3d 956, 967 2 (Fed. Cir. 2002). The written description requirement “requires a description of an invention, not an indication of a result that one might achieve if one made that invention.” Regents of the University of California v. Eli Lilly & Co., 119 F.3d 1559, 1568 (Fed. Cir. 1997); see also Novozymes A/S v. DuPont Nutrition Biosciences APS, 723 F.3d 1336, 1350 (Fed. Cir. 2013) (“A patent ...‘ is not a reward for the search, but compensation for its successful conclusion.’ ... For that reason, the written description requirement prohibits a patentee from ‘leaving it to the ... industry to complete an unfinished invention.’” (citations omitted)). Accordingly, the specification lacks adequate written description for the recited SLP-76 polypeptides , or the CART cells that contain them . Claims 53 and 58 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 rejected claims recite percent identities of SLP-76 peptides. A PHOSITA could envision sequences that met the percent identity requirement . Moreover, by using conservative substitutions, a PHOSITA could likely envision sequence s having the same tertiary structure as the SLP-76 peptide. However, there is no teaching that the conservation of structure (whether in the DNA or encoded polypeptide) would be a surrogate for conservation of SLP-76 function . Specifically , there is no teaching as to which residues of the in the recited peptides could be altered while still conserving the function of the encoded polypeptide. The specification demonstrated the recited function for the polypeptide s encoded by SEQ ID NO ’s , but offered no teaching as to what regions of the recited protein were critical for conservation of the recited function and which regions could be modified. Rather, the specification leaves it to others to discover the nature and scope of substitutions, deletions, and insertions that can be made to arrive at the recited sequence identity that additionally allows for SLP-76 activity. A pplicants may attempt to use BLAST homology data to argue that a PHOSITA would be able to address the issue, but the evidence is accorded little weight and characterized as an invitation to experiment. E ven though the DNA/polypeptides that could be envisioned by the PHOSTIA could be easily tested as set forth in the specification for conservation of the recited function, this was not enough to describe the structure so that a PHOSITA could determine beforehand whether or not a particular structure meets the functional requirements. Here , since SLP-76 variant s are claimed by percent identity and function of the expressed protein . However, a PHOSITA cannot determine if the peptides with the recited percent identities produce a protein that accomplished the recited function from the specification itself in order to meet the written description requirement. 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 appl icant regards as his invention. Claim s 46-65 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. Terms criteria of the terms “overexpress” or “elevated” with regard to levels of SLP-76, or “target antigen expressed at a low density” or “low density CAR polypeptide” are undefined. Specifically, these terms are relative term s which renders the claim indefinite. The terms are not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. The following is a quotation of 35 U.S.C. 112(d): (d) REFERENCE IN DEPENDENT FORMS.— Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers. The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph: Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers. Claim 57 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. Claim 57 recites a method of enhancing activation of the isolated recombinant cell of claim 46 , but claim 46 recites a composition comprising an isolated recombinant cell. Therefore, method claim 57 does not further limit the composition of claim 46. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements. Claim Rejections - 35 USC § 103 The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action: A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made. Claim s 46-65 are rejected under 35 U.S.C. 103 as being unpatentable over Shim et al., J lmmunol, 1 March 2011, Vol 186 No 5 Pages 2926-2935 ( Shim ) , in view of Linder et al., Sci Adv. 20 May 2020, Vol 6, No 21, (pp 1-8) ( Linder ) and WO 2020190771 ( WO 771 ) Shim teaches the r ole of SLP-76 and LAT in the PI3K signaling pathway in activated T cells . Shim examines the role of the association of these two molecules on the activation of PI3K signaling cascade. Experiments were done to determine the role of SLP-76, either wild-type, tyrosine mutants, or membrane-targeted forms of various SLP-76 constructs, on the membrane localization and phosphorylation of Akt, which is an event downstream of PI3K activation. Reconstitution studies with these various SLP-76 constructs in a Jurkat variant cell line that lacks SLP-76 or linker for activation of T cells (LAT) show that the activation of PI3K pathway following TCR ligation requires both SLP-76 and LAT adaptor proteins. The results suggest that SLP-76 associates with p85 after T cell activation and that LAT recruits this complex to the membrane, leading to Akt activation. Specifically, Shim discloses a composition comprising an isolated recombinant cell modified to overexpress and/or contain elevated levels of a SLP-76 polypeptide ( pg 2930 col 2 para 3; "To examine whether SLP-76 association with LAT or membrane targeting of SLP-76 is required for the Pl3K signaling after TCR ligation, SLP-76--deficient J14 cells were reconstituted with SLP-G2 (Gads binding domain mutant of SLP-76; consequently not associated with LAT) or TM-SLP-G2 (SLPG2 fused to LAT TM; consequently membrane-targeted). Expression of SLP-76 Wt and TM-SLP-G2 constructs, but not the SLP-G2 construct alone, reconstituted the TCR- and TCR/CD28-induced PI3K signaling pathways in J14 cells"; pg 2927 col 1 para 3; 'The plasmids carrying Wt SLP-76 and its various tyrosine mutants cloned into a modified pEF -Bos vector with an N-terminal sequence encoding the flag epitope were provided"), wherein the recombinant cell is capable of being activated by a target antigen expressed at a low density (Pg 2927 col 1 para 1; "Results from the study not only show that TCR-induced Pl3K/Akt activation is dependent on membrane translocation and tyrosine phosphorylation of SLP-76, but that LAT is also required for the localization of SLP-76 to the membrane. Collectively, these results suggest distinct roles of two adaptor molecules in the activation of Pl3K signaling pathway following TCR ligation: SLP-76 for membrane translocation of p85 and LAT for membrane translocation of SLP-76"). Shim discloses that recombinant cell modified to overexpress and/or contain elevated levels of a SLP-76 polypeptide ( pg 2930 col 2 para 3). Shim does not explicitly disclose the isolated recombinant cell further comprises a T cell receptor (TCR) polypeptide wherein the TCR polypeptide has a binding affinity for the target antigen . However, Lindner discloses that the isolated recombinant cell further comprises a T cell receptor (TCR) polypeptide wherein the TCR polypeptide has a binding affinity for the target antigen ( pg 2 col 2 para 2; "Endogenous TCRs recognize peptide:major histocompatibility complex (MHC) antigen through a highly complex and interconnected process involving receptor components a s well as intracellular kinases, substrates, and coreceptors"). Lindner further discloses that isolated recombinant cell comprises a TCR polypeptide, and wherein the target antigen is expressed by a target cell and presented to the TCR polypeptide by an antigen-presenting cell (APC) ( pg 2 col 2 para 2). Lindner further discloses that the isolated recombinant cell comprises an endogenous TCR polypeptide ( pg 2 col 2 para 2; "Endogenous TCRs recognize peptide:major histocompatibility complex (MHC) antigen"). Lindner further discloses that the isolated recombinant cell comprises a CAR polypeptide, and wherein the target antigen is expressed by a target cell ( pg 1 col 1 para 1; "solid tumor-targeted CART cells"). Lindner further discloses that the target cell is a cell correlated to a proliferative disease, a hematological malignancy ( pg 1 col 1 para 1; "hematologic malignancy-targeted CART cells"). Lindner further discloses that the target cell is a cancer cell ( pg 1 col 1 para 1; "solid tumor-targeted CART cells"). An artisan of ordinary skill in the art would have recognized that target antigen-MHC complex interaction with endogenous TCRS were the standard means by which a TCR recognized an antigen. Consequently, it would have been obvious for one of ordinary skill in the art to combine intracellular signaling pathway components, such as SLP-76, as disclosed by Shim, with the isolated recombinant cell further comprises a T cell receptor (TCR) polypeptide wherein the TCR polypeptide has a binding affinity for the target antigen, as disclosed by Lindner, because it would have enabled an antigen-dependent pathway of TCR stimulation and intracellular signaling. See also WO 771 teaching SLP-76 containing CART cells. WO 771 teaches chimeric polypeptides including (a) an extracellular targeting domain; (b) a transmembrane domain; (c) an intracellular linker for activation of T cells (LAT) domain or SLP-76 domain; and (d) an intracellular ZAP70 domain, wherein (a)-(d) are in N-terminal to C-terminal order are provided. Chimeric polypeptides including (a) an extracellular targeting domain; (b) a transmembrane domain; and (c) an intracellular ZAP70 domain, wherein (a)-(c) are in N-terminal to C-terminal order are also provided. In some embodiments, the chimeric polypeptide further includes a hinge domain and/or a signal sequence domain. WO 771 also teaches nucleic acid molecules encoding the chimeric polypeptides and expression vectors including the nucleic acids. Isolated cells (such as T cells or natural killer cells) expressing the chimeric polypeptides and methods of treating a subject with cancer with the isolated cells are taught. In this way, those of ordinary skill could have applied an intracellular signaling pathway components, such as SLP-76, as disclosed by Shim, with the isolated recombinant cell further comprises a CAR in the manner required and in a predictable fashion for the purposes of obtaining the instant recombinant cells . As outlined above , Shim teaches the role of SLP-76 in signaling pathway in activated T cells . The secondary references are added for the proposition that CART cells are applicable to this process of SLP-76 mediate T cell activation . Specifically, the secondary references teach that the particular known technique of antigen-dependent pathway of T cell stimulation and intracellular signaling was recognized as part of the ordinary capabilities of one skilled in the art . In this manner , those of ordinary skill would have recognized that applying the known technique to SLP-76 mediate T cell activation , as taught by Shim, would have yielded predictable results. Accordingly, using SLP-76 intracellular signaling pathway components with a n isolated recombinant cell further compris ing a CAR would have been prima facie obvious. It is noted that SEQ ID NO:1 represents native SLP-76, as contemplated by the references. The claims also recite effects of SLP-76 overexpression or recombinant cell activation, e.g., claims 50, 55, or enhancing activation of the isolated recombinant cell (claim 57) , or enhancing activity of at least one T cell (claim 64). However, these effects would have been an invariable aspect of the SLP-76 expressing CAR cells as disclosed by the combination of references, see MPEP 2112.01 ( “ Products of identical chemical composition can not have mutually exclusive properties.” In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present. Id. ”). Conclusion Any inquiry concerning this communication or earlier communications from the examiner should be directed to KARL J PUTTLITZ whose telephone number is (571)272-0645 . The examiner can normally be reached on Monday to Friday from 9 a.m. to 5 p.m. If attempts to reach the examiner by telephone are unsuccessful, the examiner's acting supervisor, Gregory Emch , can be reached at telephone number 571-272-8149. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300. Information regarding the status of an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only. For more information about the PAIR system, see http://pair-direct.uspto.gov. Should you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). /KARL J PUTTLITZ/ Primary Examiner, Art Unit 1646