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 the Claims
Claims 1,17-20,23-26,66-70 and new claims 72-77 are currently pending in the Application and are examined on the merits below.
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.
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.
Claims 1, 17, 18, 20, 23-26, 66-70, 72, 73, 75-77 are rejected under 35 U.S.C. 103 as being unpatentable over Thompson (US20180319862A1) and further in view of June (WO2016126608) and Kandalaft (Journal of Translational Medicine (2012 10:157) and Lanitis et al (Cancer Immunology Research; 1(1) July 2013).
The instant claim 1 describes a “CoStAR” fusion protein which has an extracellular binding domain, linked to a transmembrane domain. The CoStAR molecule additionally comprises a CD28 signaling domain and a CD40 signaling domain.
a.) The extracellular binding domain comprises sequence of SEQ ID NO:4 and corresponds to a scFv molecule which is a “mov19” scFv molecule which binds to folate receptor 1 a. This sequence is identical to the SEQ ID NO:96 of June, as a mov19 folate receptor binding scFv molecule.
b.) The intracellular signaling domain derived from CD28 as SEQ ID NO:16. This sequence is identical to the native human CD28 designated intracellular signalling domain of Thompson as SEQ ID NO:8.
c.) The intracellular signaling domain derived from CD40 as SEQ ID NO:23. This sequence is identical to the native human CD40 derived intracellular signaling domain of Thompson as SEQ ID NO: 12.
With respect to claim 1 previously presented disclosure of Thompson describes chimeric receptor molecules which may have antigen binding domains directed to the folate receptor alpha (0021)(claim 1-16, 29) as an antigen expressed by cancer cells (tumor). Significantly with regards to the instant claimed invention the disclosure of Thompson describes chimeric receptor molecules that comprise transmembrane domain derived from the CD28 molecule fused to CD28 intracellular signalling domain , fused to CD40 intracellular signalling domain which provide increased or improved activity, efficacy and/or persistence (abstract)(claims 1-29). The disclosure provides for “conventional” CAR molecules which comprise on the same chain a costimulatory signalling domain and an activating domain derived from for example CD3zeta as in the claim structure (Thompson) that follows claims 5-8-9-16-17-19-29 (also 0137, 0138). The disclosure of Thompson thus specifically in the claim set describes embodiments of the invention which may comprise a FR-alpha binding domain, a CD28 transmembrane domain and intracellular signalling domain and a CD40 intracellular signalling domain, with (conventional) or without an “activating” CD3 zeta intracellular signalling domain (claims p64-66). ). The specification of Thompson also indicates (0009) “in some of any such embodiments the chimeric receptor further contains an activating cytoplasmic signalling domain”. Thus Thompson envisions intracellular signalling domains that comprise both CD40 and CD28 costimulatory molecules and an extracellular antigen binding domain with and without intracellular activating (CD3 zeta) derived signalling components (also 0011, 0012). “Multimeric” chimeric receptor complexes comprising a first and second chimeric receptor are described likewise utilizing TRAF-6 (as CD40) inducing domains (0026-0028)(0137,0138). “Transgenic TCR” and functional “non-TCR” antigen receptor are embodiments of the multimeric composition of the invention of Thompson (0028).
Additionally the disclosure of Thompson describes the mechanisms of action of the TCR/ T cell activation as understood in the art (0123-0125). The disclosure indicates that with regards to the invention of Thompson, the chimeric receptor , such as CAR does not include the co-stimulatory signal, in which case the TRAF-6 inducing (CD40) signaling domain may be provided on a second chimeric receptor such as an additional CAR, expressed in the same cell (0128). Multimeric chimeric receptor complex are described which may comprise (0363) independently a TCR component or a transgenic TCR (0372, 0377). Thus the disclosure of Thompson describes chimeric antigen receptor molecules which may have antigen binding domains directed to the folate receptor alpha (0021) as an antigen expressed by cancer cells (tumor). Thompson describes that the antifolate receptor ligand binding domain may be linked to a spacer which joins to a transmembrane domain (0022) and an intracellular signalling domain which is derived from the signalling domains of CD40 (0006) and additional signalling domain derived from CD28 for example (0012). The intracellular signalling domain may additionally comprise the signaling domain of CD3 zeta, or may not include any additional stimulatory signaling domain in addition to the CD40 and CD28 signaling domains (0011). Thus structurally the disclosure of Thompson describes a chimeric receptor with [folate-ra directed binding domain/CD28 extracellular domain/CD28 transmembrane domain/CD28 intracellular signaling domain/CD40 intracellular signaling domain].
The disclosure of Thompson comprehensively describes chimeric receptor molecules that are in embodiments identical to the claimed molecules in claims 1, for instance leaving out the specifically claimed scFv antigen binding domain sequence, but including the particular FolR1a target as a cancer antigen.
The disclosure of June describes a chimeric antigen receptor directed to the Fol-R1a molecule which utilizes the scFv mov19 as an antigen binding domain, which may comprise a first and second intracellular signaling domain derived from CD28 and CD40 molecules (p6, 20-30)(p103,p104) . Likewise the disclosure of Kandalaft describes a proposed phase I clinical trial that utilizes “conventional” CAR-T cells comprising extracellular antigen binding domain directed to the folate receptor alpha molecule for recurrent ovarian cancer (abstract). Folate receptor alpha directed CAR-T cells utilize the mov-19 scFv molecule as a targeting agent (figure 1). One may additionally look to the disclosure of Lanitis which describes Mov-19 scFv derived anti-FRa “costimulatory” CAR molecules that are similar to the claimed “CoStAR” molecules , comprised of MOV19 scFv antigen binding domain, and CD28 transmembrane-intracellular signalling domains (“F-28 CAR”)(figure 1B). Notably the domains are devoid of CD3zeta primary signalling domains, with additional primary signalling (CD3-zeta) provided by additional CAR molecule co-expressing a 1st generational CAR molecule which only comprised a CD3-zeta intracellular signalling domain. The disclosure of Lanitis particularly describes that the scFv molecules utilized for the primary and costimulatory CAR molecules were “prevalidated” (as MOV-19scFv) for example. It would be obvious to utilize the prevalidated mov19 scFv of June and Kandalaft and Lanitis as an antigen binding moiety in the CAR of Thompson for purpose of utilizing a known previously disclosed functional component that has been successfully tested and incorporated into a CAR molecule/costimulatory CAR molecule.
With respect to the claims 17, 18, 20 the disclosure of Thompson and June describe chimeric antigen receptor with identical composition to that of claim 1, in which the antigen binding domain may be linked to the transmembrane domain separated by a linker of 2-10 amino acids (0146) or alternatively may include a spacer between the scFv and transmembrane domain which functionally provides for improved responsiveness of a cell comprising the receptor after engagement of the chimeric antigen receptor upon binding of cognate antigen (0155). The disclosure goes on to describe suitable spacer lengths as 10-229 amino acids and provides examples of requisite spacers and reference sources of other variants. It would be obvious to thus provide a chimeric receptor which comprises a spacer between the scFv and C terminal functional components for the purposes of optimizing effector cell – target cell interaction parameters such as distance which correlates to optimal receptor engagement and target cell killing.
In regards to the claims 23 and 24 the disclosure of Thompson describes that spacer may comprise a domain as SEQ ID NO: 1 for example (an IgG4 hinge) which is identical to the N terminal 12 amino acid of the instant SEQ ID NO: 13.
With regards to the claims 25 and 26 and the elected species of CD28/SEQ ID NO:11 “transmembrane domain sequence of” the disclosure of Thompson describes that the transmembrane domain may comprise the CD28 transmembrane domain as SEQ ID NO: 6 p42 as identical to “the transmembrane domain sequence of” instant SEQ ID NO:11 (CD28).
The instant claims 66 and 67 describe a cell which comprises a “CoStAR” of claim 1. The cell expresses the CoStAR on “a surface of the cell”. The claims 68-70 go on to more specifically describe the cell of interest as a T cell for instance, more specifically a TIL (tumor infiltrating lymphocyte) and wherein the cell co-expresses a CAR or a “TCR”.
With regards to the instant claims 66-70, for example both Thompson and June recognize tumor infiltrating lymphocytes as population of T cells in which CAR/Costimulatory CAR of the invention may be expressed in (June p160, 10-15)(Thompson, 0180). Thus the CAR/Costar molecules of June utilizing the Mov19scFv molecule as a targeting moiety is expressed as a vector (nucleic acid) for the purpose of expressing the protein molecule in a cell (p6, 1-30). Additionally the mov19 targeted CAR molecules were found to target tumors when incorporated into T cells in mouse cancer models, therefore these T cells comprising the CAR molecules qualify as “TILs” tumor infiltrating lymphocytes, as by definition to reduce the tumor size, the cells must physically “infiltrate” the tumor. T cells are lymphocytes. Thus in both instances it would be obvious to utilize TIL as a T cell type in which disclosed CAR/Costimulatory CAR of the invention may be expressed for the purposes of conferring enhanced tumor targeted cell homing and killing. It is additionally noted that conventional “TIL” as a T cell derived entity also express naturally occurring rearranged TCR on their surface. It is noted that in embodiments of the invention as claimed instantly in 70 for example the Applicant envisions utilizing the targeted “Costar” molecule, which comprises at least CD40 and CD28 intracellular signalling components, in conjunction with at least a minimal “TCR” or “CAR” molecule. Thus none of Applicant’s cellular claims are limited to “single component” exogenously introduced systems, with an additional CAR molecule or TCR providing the primary activation signal required (primarily CD3zeta mediated) to fully activate re-directed T cells.
Regarding the new claim 72 as indicated above the CAR molecules of Thompson in embodiments may or may not include a stimulatory/activating intracellular signalling moiety such as CD3-zeta for example.
Regarding the new claim 73 the disclosure of Thompson provides that CAR molecules of the invention may additionally comprise a signal peptide/signal sequence as part of for example a nucleotide sequence which encodes the CAR molecule thereby providing a protein which comprises the signal peptide-CAR protein sequence. It would thus be obvious to provide the instant claimed co-stimulatory CAR molecule with a signal peptide for the purpose of providing appropriate cellular targeting of the translated protein.
Regarding the new claim 75 and the incorporation of SEQ ID NO: 13, the sequence provided is the entire sequence of IgG4 hinge Fc domain fused at the C terminus to the transmembrane region of the CD28 molecule. As previously provided the disclosure of Thompson provides extracellular spacer molecules for CAR constructs which comprise for example IgG4 (SEQ ID NO:4 of Thompson see alignment below with SEQ ID NO:13). The disclosure of Thompson further provides that “In some embodiments , the spacer has a sequence of amino acids that exhibits at least 85 % , 86 % , 87 % , 88 % , 89 % , 90 % , 91 % 92 % , 93 % , 94 % , 95 % , 96 % , 97 % , 98 % , 99 % or more sequence identity to any of SEQ ID NOs : 1 - 5 .” (0156). Furthermore the remaining sequence of the instant SEQ ID NO:13 is derived as the transmembrane domain of CD28 molecule (FWVLVVVGGVLACYSLLVTVAFIIFWV, Uniprot PID= 10747.1). Thompson clearly indicates use of this domain in a chimeric receptor of the invention (0154). It would therefore be obvious to provide the combined sequences which is instantly claimed , as an extracellular spacer-transmembrane sequences previously disclosed by Thompson as useful and viable combinations.
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Therefore as indicated above regarding claims 76 and 77 and the use of the transmembrane domain of CD28 as SEQ ID NO: 15 the disclosure of Thompson clearly indicates that CD28 is a preferred source of transmembrane domain for chimeric receptor of the invention (PID= 10747.1, Thompson 0154) and disclosed as SEQ ID NO:6. It would be obvious to provide the selected sequence as a known transmembrane domain previously successfully utilized in CAR molecules as disclosed by Thompson.
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Claim 19 is rejected under 35 U.S.C. 103 as being unpatentable over Thompson and June and Kandalaft and Lanitis as applied to claim 17 above, and further in view of Lee (Immunity 2015 August 18; 43(2): 227-239. Doi:10.1016).The disclosures of T do not describe the exact sequence of SEQ ID NO: 8 (AAAGSGGSG), 9 amino acids as an appropriate linker to utilize between the antigen binding domain and downstream functional components (extracellular-transmembrane-cytoplasmic) in a Costar molecule for example or as a linker that may be used between components of a scFv such as between a VH and VL fragment. The disclosure of Lee is concerned with determination of the mechanical switch mechanism which is engaged upon TCR binding to cognate ligands. The disclosure of Lee describes flexible linker sequences utilized to separate functional components of fusion proteins involved in signalling of the TCR complex (p5). One such linker utilized is identical to the sequence of SEQ ID NO:8 (supplemental contents, figure 2B) and it would be obvious to utilize known functional linker sequences as described by Lee for the purpose of separating components of the antigen binding molecule from the downstream components and providing optimal distance between the engaged fusion receptor and the target cell antigen.
Claim 74 is rejected under 35 U.S.C. 103 as being unpatentable over Thompson, June Kandalaft and Lanitis and as applied to claim 1 above, and further in view of Burger (US7507412B2).
The combined disclosure of Thompson, June, Kandalaft and Lanitis do not provide a human Oncostatin-M leader sequence. Thompson does however, as described above indicate chimeric receptors may comprise leader sequences. The disclosure of Burger provides fusion protein expression constructs which comprise leader sequences derived from the human oncostatin M DNA/protein sequences. (Example 2, Col 16)(SEQ ID NO:12). It would be obvious to utilize a known leader sequence when wanting to produce a fusion protein for the purposes of successfully targeting and ultimately providing for appropriate amounts of the desired protein. One of ordinary skill in the art would utilize known sequences from previously described leader sequences in the art for the purposes of successfully producing such a fusion protein as the applicant has thus done.
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.
Claims 1 ,17-20,23-26 and 66-70, 72-77 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1-17, 21-35 of copending Application No. 17361621 (reference application) and further in view of Thompson, June, Lanitis, Kandalaft and Lee and Burger. Although the claims at issue are not identical, they are not patentably distinct from each other. The reference patent claims for example claim 1 describes CoStar molecules which comprise an antigen binding domain directed to a tumour associated antigen and a first and second costimulatory signalling domain. The Costar may be comprised of for example CD28 or CD40 (claim 4). Claim 6 indicates that the folate receptor may be targeted by a single chain antigen binding domain directed to a tumour antigen.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claim 1 ,17-20,23-26 and 66-70, 72-77 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 44-70, 72 of copending Application No. 17936102 (reference application) further in view of Thompson, June, Lanitis, Kandalaft and Lee and Burger. Although the claims at issue are not identical, they are not patentably distinct from each other. The claims of the reference Application describe Costar molecules significantly identical to the instant Costar molecules , with only the extracellular antigen binding domain different. It would be obvious to utilize instead a FolR1 binding Mov19 scFv antigen binding domain as described by June, Kandalaft and Lanitis for example.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claim 1 ,17-20,23-26 and 66-70, 72-77 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1-14 of U.S. Patent No. 11945876 further in view of Thompson, June, Lanitis, Kandalaft and Lee and Burger. Although the claims at issue are not identical, they are not patentably distinct from each other. The reference patent claims describe Costar molecule which comprise a different antigen binding domain directed to CEA as well as transmembrane-intracellular signalling domain (1) derived from ICOS. The CD40 costimulatory domain is included as a second intracellular signalling domain. The combined disclosure of the additional references makes obvious the instantly claimed Costar structure as indicated above.
Claim 1 ,17-20,23-26 and 66-70, 72-77 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1-13 of U.S. Patent No.12187778 further in view of Thompson, June, Lanitis, Kandalaft and Lee and Burger. Although the claims at issue are not identical, they are not patentably distinct from each other. The claims of the reference Application describe Costar molecules significantly identical to the instant Costar molecules , with only the extracellular antigen binding domain different. It would be obvious to utilize instead a FolR1 binding Mov19 scFv antigen binding domain as described by June, Kandalaft and Lanitis for example.
Response to Arguments- Claim Rejections - 35 USC § 112
Applicant’s amendments to the claims have obviated the previously applied rejection for lack of antecedent basis and therefore this rejection is removed.
Response to Arguments- Claim Rejections - 35 USC § 103
In reply to previously Applied rejections of record Applicant traverses. In initial arguments Applicant provides that the cited references do not provide expectancy for the unexpected properties of that the Applicant’s constructs exhibit. In support Applicant argues that the disclosure of June provides the instantly claimed costimulatory domains of CD40 and CD28 in a long list of 120 other costimulatory domains. Applicant further describes that the disclosure of Thompson “places no emphasis on CD28 combined with CD40” and does not disclose combining multiple costimulatory domains. The reference of June is not the primary reference regarding utilization of the claimed CD28-CD40 intracellular signalling domain, this is Thomson which emphasizes the exact combination that Applicant instantly claims as a combination selected from (4-1BB, ICOS, CD28) + CD40. Particularly as previously described the CD28-CD40 construct is claimed in the claim-set construction of Thomson. Therefore looking from Thomson to June (both of which disclose FOLR1 as a targetable cancer antigen), One would select FOLR1 and particularly MOV19 scFv as the targeting moiety with a reasonable expectation of success.
Applicant appears to claim unexpected results regarding the figure 8 and mov-19 binding moiety. Significantly the ability of the Mov-19 binding scFv to provide adequate signalling in the context of both conventional CAR molecules (June) and in Costimulatory CAR molecules (Lanitis, figures 1B and Figure2) was well established in the prior art and as previously presented in reply to arguments and Office Action of 02-11-2025. The suitability of the Mov19 antigen binding moiety is argued in response to arguments of final office action 06-02-2023. It is therefore obvious to utilize this known antigen binding domain in a CAR/Costimulatory CAR, and one would do so with a reasonable expectation of success. The “unexpected” result that the Mov-19 based CAR functions to properly activate T cells to for example proliferate in the presence of proper TCR-based stimulation (OKT3) is an expected result. It would in fact be unexpected that it would not work properly in the experimental context of figure 8.
Moving on, Applicant claims unexpected results regarding the combination of CD28 and CD40 costimulatory domains, particularly regarding the information presented in Figure 25. Significantly the arguments presented have previously addressed in response to arguments of 06-02-2023. As previously presented, the disclosure of Thomson clearly envisions the use of all three (CD28, 4-1BB or ICOS) as intracellular signalling domains in combination with at least CD40. Regarding the purported unexpected results with respect to figure 25 briefly as previously presented the constructs of the figure are targeting a mesothelin antigen and do not therefore comprise the MOV19 antigen binding domain. Thus the CTP190 and CTP192 are comparable in composition of the CAR to each other but are not what is instantly claimed. It is additionally noted that the CTP192 (4-1BB-CD40) data appears to include no error bars, making comparison between different conditions difficult. As MPEP 716.02(d) indicates “objective evidence of nonobviousness must be commensurate in scope with the claims which the evidence is offered to support. Furthermore even if the disclosed figure indicates that CD28-CD40 provides superior proliferative results compared to for example 4-1BB-CD40 constructs, explanations for the differences exist. The 4-1BB and CD40 intracellular signalling domains are both known to recruit TRAF proteins to the receptor interface. CD28 on the other hand is unrelated to the TNSFR superfamily molecules and recruits a separate entourage of intracellular signalling accessory molecules to the receptor intracellular interface, ultimately activating separate and unique T cell activation cascades. Therefore one may in fact expect that the synergistic effect of the CD28-CD40-CD3zeta T cell activation cascade would be superior to that of a 4-1BB-CD40-CD3zeta T cell activation cascade in which marginally 4-1BB and CD40 activate the same downstream signals, and potentially compete for limited TRAF molecules at the receptor interface.
Applicant further indicates that the particular linker provided in the construction of claim 17 AAAGSGGSG for example disclosed by the reference of Lee as an intracellular membrane proximal spacer/linker is not reasonably expected to be utilized as an extracellular spacer domain with a reasonable expectation of success. Applicant appears to thereby describe that the invention is ultimately involved with this short linker sequence which is inserted in various constructs C terminal to the scFv binding moiety of the costimulatory receptor construct. Applicant’s arguments have been fully considered but are not found convincing. The Applicant has utilized the exact same biological sequence intended to perform the same function “linker” or “spacer” as in the cited reference. A prima facie case of obviousness may be made when chemical compounds have very close structural similarities and similar utilities. "An obviousness rejection based on similarity in chemical structure and function entails the motivation of one skilled in the art to make a claimed compound, in the expectation that compounds similar in structure will have similar properties." In re Payne, 606 F.2d 303, 313, 203 USPQ 245, 254 (CCPA 1979). See In re Papesch, 315 F.2d 381, 137 USPQ 43 (CCPA 1963) (discussed in more detail below) and In re Dillon, 919 F.2d 688, 16 USPQ2d 1897 (Fed. Cir. 1990) (discussed below and in MPEP § 2144) for an extensive review of the case law pertaining to obviousness based on close structural similarity of chemical compounds. MPEP 2144.09 I. See also MPEP § 2144.08, subsection II.A.4.(c). In the instant case, Applicant claims the exact amino acid sequence (structure) that is utilized in the reference of Lee. The fact that the spacer is utilized extracellularly does not appear to the Examiner to impart any further characteristics and at worst the intracellular spacer configuration would be expected to be at least be reasonably “similar” functionally when compared to the same sequence expressed extracellularly , and as Applicant admits in the claim , the intended function is that of a linker/spacer.
Applicant further provides new claims 72-77 and describes that said claims are not made obvious by the cited references. The claims are rejected above with rationale provided.
Conclusion
Summary: NO claims are 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.
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/BRIAN HARTNETT/ Examiner, Art Unit 1644
/JANET L ANDRES/ Supervisory Patent Examiner, Art Unit 1671