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 .
Application Status
Applicant’s remarks and amendments to the claims filed October 7, 2025 are acknowledged. Claims 1, 7, and 67 were amended. Claims 1, 6-7, 12, 67-69, and 71-76 are pending and under examination herein.
Withdrawn Rejections
Applicant’s amendments to claims 1, 7, and 67 to strike all previously recited membrane targeting amino acid sequences, with the exception of “KRas4A-C22 (SEQ ID NO: 16),” overcome the § 103 rejections raised in the prior action over Huang, Ahmadian, GenPept, Walker, and Mori. None of the cited prior art appears to teach or suggest the instantly recited membrane targeting amino acid sequence, i.e., KRas4A-C22 corresponding to SEQ ID NO: 16). The aforementioned rejections are withdrawn, accordingly.
Applicant’s remarks and amendments have been thoroughly reviewed, but are not persuasive to place the claims in condition for allowance for the reasons that follow. Any rejection or objection not reiterated herein has been overcome by amendment.
Priority
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. Applicant has not complied with one or more conditions for receiving the benefit of an earlier filing date under 35 U.S.C. 119(e) as follows:
The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of 35 U.S.C. 112(a) or the first paragraph of pre-AIA 35 U.S.C. 112, except for the best mode requirement. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994).
The disclosure of the prior-filed provisional application, Application No. 62/751,968, filed October 29, 2018, fails to provide adequate support or enablement in the manner provided by 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph for one or more claims of this application. Specifically, Application No. 62/751,968 fails to disclose the membrane targeting amino acid sequence recited in claims 1, 7, and 67. The first disclosure of the membrane targeting amino acid sequence recited in claims 1, 7, and 67 is in Application No. PCT/US2019/058447, filed October 29, 2019 (pg. 53, line 31). Because the subject matter of all claims under examination is first disclosed in Application No. PCT/US2019/058447, all claims have an effective filing date of October 29, 2019.
Notice to Joint Inventors
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.
Claim Rejections - 35 USC § 103 – Huang in view Ahmadian, GenPept, Walker, Cox, and Laporte
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.
Claims 1, 6-7, 12, 67-69, and 71-72 are rejected under 35 U.S.C. 103 as being unpatentable over Huang (Huang et al., 1993, Molecular and Cellular Biology, 13(4), p. 2420-2431; of record) in view of Ahmadian (Ahmadian et al., 1996, The Journal of Biological Chemistry, 271(27), p. 16409-16415; of record), GenPept (Accession: NP_000258.1; neurofibromin isoform 2 [Homo sapiens]; updated 21 October 2018; of record), Walker (Walker and Upadhyaya, 7 May 2018, Vol. 22, No. 5, pg. 419-437; of record), Cox (Cox et al., 15 April 2015, CCR Focus, 21(8), pg. 1819-1827), and Laporte (Laporte et al., WO 2016/041093 A1, published 24 March 2016). The rejections that follow are new and necessitated by Applicant’s amendments to the claims.
Regarding claim 1, Huang teaches that activating mutations in ras, and thus, aberrant ras signaling, are among the most common correlates of human malignancy (pg. 2420, left col.). Huang teaches that “elucidation of the ras signalling pathway is therefore of considerable interest” (pg. 2420, left col.). Huang teaches that ras GAP accelerates ras intrinsic GTPase activity and promotes formation of inactive ras (pg. 2427, right col.). Huang teaches that ras (“p21ras”) is associated with the plasma membrane, whereas ras GAPs, including NF1, do not appear to localize to the plasma membrane (pg. 2420, right col.; pg. 2427, right col.). Huang teaches that ras GAP must be localized to the plasma membrane in order to interact with ras and exert GAP effects (pg. 2420, right col.).
Huang teaches a recombinant polypeptide comprising an NF1-GRD fused to a KRas membrane targeting amino acid sequence (“NF1GRRA” or “NF1GRRK”, FIG. 7A, pg. 2428). Huang teaches the KRas membrane targeting amino acid sequence consists of the C-terminal sequences of KRasB (FIG. 7A, Key: … “-SKDGKKKKKKSKTKCVIM (K-ras(B) tail)”). Huang teaches that the “19 C-terminal amino acids of K-ras(B), containing the CAAX motif and the polybasic domain, are sufficient to target” the NF1-GRD to the plasma membrane (pg. 2421, left col.). Huang demonstrates that the recombinant polypeptide prohibits cellular growth by negatively regulating RAS signaling, and furthermore, that the recombinant polypeptide was even “more inhibitory than the targeted C-terminal catalytic domain of ras GAP” (FIG. 7; “When targeted to the plasma membrane, NF1GRD is also growth inhibitory”, pg. 2427-2428; “Plasma membrane targeted ras GAP is growth inhibitory to NIH 3T3 fibroblasts and COS cells. This growth inhibition correlates with GAP catalytic activity, since the plasma membrane-targeted C-terminal catalytic domain or the GAP-related domain of neurofibromin is inhibitory, whereas the similarly targeted N-terminal domain is not.”, Abstract).
Huang does not teach the sequence of the NF1-GRD in the recombinant polypeptide.
Ahmadian teaches that the “true minimal domain[]” of the neurofibromin GAP-related domain (GRD) corresponds to amino acids 1248-1477 of neurofibromin (“NF1-230”, Abstract; pg. 16412-16413; Fig. 1). Ahmadian teaches that the minimal domain (“NF1-230”) retains enzymatic properties similar to larger portions of the NF1-GRD (“NF1-333”) and full-length neurofibromin (pg. 16412, right col.; pg. 16413, left col.; Table 1; Fig. 1). The amino acid sequences taught by Ahmadian for the minimal domain (“NF1-230”, amino acids 1248-1477) and NF1-333 (amino acids 1198-1530) are aligned in Figure A below with the known sequence of NF1 taught by GenPept, and instant SEQ ID NO: 2. The instantly claimed ranges of SEQ ID NO: 2 each I) have 100% identity to the known sequence of NF1 taught by GenPept (NP_000258.1), and II) have 100% identity to the minimal domain taught by Ahmadian (“Ahmadian_NF1_230”). Furthermore, the instantly claimed range of amino acids 1200-1532 is shifted only two residues relative to NF1-333 taught by Ahmadian (“Ahmadian_NF1_333”), which Ahmadian teaches has “100%” of wild-type GAP properties (Table 1). Taken together, Ahmadian and GenPept provide predictability for, and the sequences to prepare, a functional NF1-GRD selected from any range of amino acids in NF1 encompassing at least the known, minimal domain of the NF1-GRD taught by Ahmadian, i.e., amino acids 1248-1477.
FIGURE A
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Regarding the NF1-GRD, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have substituted the NF1-GRD of Huang, for an NF1-GRD selected from a range of known amino acids in NF1 encompassing the known NF1-GRD and true minimal domain thereof taught by Ahmadian. It would have amounted to selecting an NF1-GRD from a range of known amino acids encompassing the NF1-GRD, and which contains the residues known to be required for the NF1-GRD’s ras GAP function, by known means, to yield predictable results. Together, Ahmadian and GenPept provide predictability for preparing a functional recombinant polypeptide by selecting any range of amino acids encompassing at least the known, minimal domain of the NF1-GRD (i.e., amino acids 1248-1477). The skilled artisan would have had a reasonable expectation of success in substituting Huang’s NF1-GRD, with one of amino acids 1200 to 1532 of SEQ ID NO: 2 or amino acids 1222 to 1503 of SEQ ID NO: 2, and retaining ras GAP function because I) the complete sequence of NF1 was known as evidenced by GenPept, II) the sequences of the complete NF1-GRD (i.e., amino acids 1198-1530) and minimal domain of NF1-GRD that retains ras GAP function (i.e., amino acids 1248-1477) were known as evidenced by Ahmadian, and III) the instantly claimed ranges are 100% identical to the known NF1 sequences and fully encompass the minimal domain taught by Ahmadian. A skilled artisan, seeking to prepare the polypeptide of Huang for the purposes of “elucidation of the ras signalling pathway” or developing a potent inhibitor of cellular growth, would have been motivated to substitute the elements because Huang was silent as to the sequence of the NF1-GRD in the recombinant polypeptide used to inactivate ras and prohibit cellular growth, and GenPept and Ahmadian provide the sequences.
Huang teaches that the recombinant polypeptide comprises a myc tag (Fig. 7A), and does not teach that the recombinant polypeptide consists of an NF1-GRD fused directly to a KRas membrane targeting amino acid sequence.
Walker teaches that Neurofibromatosis type 1 (NF1) is an inherited multisystem disorder with “[n]o effective therapy” (pg. 419; “2. NF1 – a multisystem disorder”, pg. 420). Walker teaches that the root cause of NF1 pathology is neurofibromin deficiency that leads to increased ras signaling (pg. 419, right col.). Walker teaches that “the only well-established function of neurofibromin is the downregulation of RAS as a RAS-GAP;” an activity that Walker teaches is contained within the highly conserved GAP-related domain (pg. 422-423). Walker teaches that “even a modest decrease in RAS signaling could be beneficial for NF1 patients” (pg. 423, right col.). Walker describes therapeutic approaches designed to restore NF1 function and decrease ras signaling (“5. Possible therapeutic approaches for NF1”, pg. 423-431), including a gene therapy approach to deliver “a truncated version of the NF1 gene retaining an appropriate level of function” (“5.1.3. Gene therapy”, pg. 427). Walker teaches that delivery of a truncated NF1 gene would circumvent the need to increase cargo capacities of available vectors or develop novel delivery systems, which would otherwise be required to deliver the large, full-length NF1 cDNA (“5.1.3. Gene therapy”, pg. 427). Walker teaches that the approach will “replace mutant alleles and thereby restore neurofibromin levels and function” (“5.1.3. Gene therapy”, pg. 427).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have fused the NF1-GRD rendered obvious in paragraph 10 above, directly to the KRas membrane targeting amino acid sequence, in an effort to prepare a truncated NF1 retaining ras GAP function, with membrane localization effective to decrease ras signaling, and small enough to be delivered in existing vectors as taught by Walker. It would have amounted to removing an intervening myc tag from an obvious recombinant polypeptide, by known means to yield predictable results. The skilled artisan would have had a reasonable expectation of success of retaining the resultant recombinant polypeptide’s ras GAP function and plasma membrane targeting because the NF1-GRD and KRas membrane targeting amino acid sequence have such functions separately, and as evidenced by Huang, they also retain such functions when combined in the same polypeptide. The skilled artisan, familiar with the teachings of Walker, would have recognized the therapeutic potential of the recombinant polypeptide of Huang for the disorder taught by Walker, but would also have recognized that the size limits of readily available vectors require streamlining of the cDNA encoding the recombinant polypeptide. Thus, the skilled artisan would have been motivated to prepare a recombinant polypeptide in which the NF1-GRD was fused directly to the KRas membrane targeting amino acid sequence, thereby reducing the overall size of the recombinant polypeptide, and circumventing the need to increase cargo capacities of available vectors or develop novel delivery systems, which would otherwise be necessary to deliver larger NF1 gene therapy constructs.
As stated above, the KRas membrane targeting amino acid sequence of Huang is from KRasB. Thus, Huang also does not teach a KRas4A membrane targeting amino acid sequence consisting of SEQ ID NO: 16 (i.e., LKKISKEEKTPGCVKIKKCIIM).
Cox teaches the C-terminal membrane targeting sequence of both KRas4A and KRas4B (Fig. 1). Cox’s KRas4B membrane targeting sequence comprises 100% identity to the KRasB membrane targeting sequence of Huang (“KHKEKMSKDGKKKKKKSKTKCVIM,” Fig. 1), and as shown in Fig. B below, Cox’s KRas4A membrane targeting sequence comprises 100% identity to instant SEQ ID NO: 16. Cox teaches that “RAS association with the plasma membrane and with other membrane compartments upon which signaling occurs… is promoted by a well-described series of posttranslational modifications at RAS C-terminal CAAX motifs” (pg. 1820). Cox teaches that the KRas4A membrane targeting motif consists of “both a palmitoylated cysteine and two short polybasic regions flanking that acylated cysteine,” pg. 1822-1833, Fig. 1). These features are highlighted in Cox’s Fig. 1, and preserved in Fig. B below.
Laporte teaches a fusion polypeptide comprising a protein to be targeted to the plasma membrane (“Renilla GFP or Renilla Luc”), and a plasma membrane targeting sequence (“plasma membrane targeting moiety”), wherein the plasma membrane targeting sequence may be the hypervariable region (HVR) of KRas4A or KRas4B (“the PM targeting moiety comprises a CAAX motif… The last C-terminal residues of… KRAS4A or KRAS4b… are depicted below…”)(pg. 27, line 28 to pg. 29, line 2). Laporte teaches the “putative minimal plasma membrane targeting region” within the HVR of KRas4A, which is italicized in Fig. B below (pg. 28, line 34-37).
FIGURE B
QYRLKKISKEEKTPGCVKIKKCIIM Cox et al., C-terminal KRas4A sequence
KISKEEKTPGCVKIKKCIIM Laporte et al., C-terminal KRas4A sequence
LKKISKEEKTPGCVKIKKCIIM SEQ ID NO: 16
Regarding the membrane targeting amino acid sequence, it would have been obvious to one skilled in the art before the effective filing date of the claimed invention to have prepared a KRas4A membrane targeting sequence consisting of SEQ ID NO: 16 based on the teachings of Cox and Laporte, and to have substituted Huang’s KRas membrane targeting sequence in the recombinant polypeptide rendered obvious above in paragraph 12 with the prepared KRas4A membrane targeting sequence. It would have amounted to substituting a known KRas membrane targeting sequence for a KRas membrane targeting sequence with motifs sufficient to fulfil the same purpose, by known means to yield predictable results. The C-terminal motifs through which KRas4B and Kras4A associate with the plasma membrane were well known based on the prior art. The skilled artisan would have been able to prepare a KRas4A membrane targeting sequence to fulfill the same purpose as Huang’s KRasB membrane targeting sequence, because the prior art teaches the complete KRas4A membrane targeting sequence (see Cox, Fig. 1), and the specific motifs therein which are important for membrane association (see bolded, underlined, and italicized features in Fig. B above). To arrive at SEQ ID NO: 16 based on Cox and Laporte, the skilled artisan would only need to remove three amino acids (“QYR”) from the complete sequence of Cox. Because this shortened KRas4A membrane targeting sequence contains the motifs taught by Cox and Laporte important for membrane targeting, the skilled artisan would have had a reasonable expectation of success that substituting the two sequences (i.e., Huang’s KRasB sequence for SEQ ID NO: 16) would preserve membrane localization of the recombinant polypeptide. The skilled artisan would have been motivated to substitute Huang’s KRasB membrane targeting sequence for a KRas4A membrane targeting sequence, because Laporte indicates that both KRas4A and KRas4B membrane targeting sequences are suitable for targeting a fusion protein to the plasma membrane. The skilled artisan would have been motivated to prepare a shortened but functional KRas4A membrane targeting sequence based on the teachings of Walker regarding size limits of readily available vectors.
Regarding claim 7, Huang teaches a recombinant nucleic acid (“plasma membrane-targeted constructs NF1GRRA and NF1GRRK”) comprising a nucleotide sequence encoding an NF1-GRD fused to a KRas membrane targeting amino acid sequence (“The C-terminal sequence of H-ras and K-ras(B), containing both signals for plasma membrane localization, were cloned onto a myc-tagged NF1GRD to give the plasma membrane-targeted constructs NF1GRRA and NF1GRRK”, FIG. 7 description, pg. 2428; “myc-tagged NF1GRD (GAP-related domain) plasmid (ptrpNF1GRD)”, pg. 2421, right col.).
As described above, Huang does not teach I) the sequence of the NF1-GRD, II) that the recombinant polypeptide consists of an NF1-GRD and KRas membrane targeting sequence, or II) that the KRas membrane targeting amino acid sequence is SEQ ID NO: 16. The obviousness of substituting Huang’s NF1-GRD for an NF1-GRD encompassing the minimal domain taught by Ahmadian, selected from a range of known residues of NF1 is described above in paragraph 10 and applied here. The obviousness of fusing the NF1-GRD directly to the KRas membrane targeting sequence (i.e., removing the myc tag of Huang) is described above in paragraph 12 and applied here. The obviousness of substituting the KRas membrane targeting sequence taught by Huang for SEQ ID NO: 16 is described above in paragraph 14 and applied here.
Regarding claims 6 and 12, “joined in-frame to the C-terminus” is interpreted as requiring the membrane targeting amino acid sequence be connected to the C-terminus of the NF1-GRD, in such a manner that the membrane targeting amino acid sequence is translated without error or disruption. Huang demonstrates that there is a measurable effect from the C-terminal membrane targeting amino acid sequences, (i.e., localization to the membrane, and reduced cellular growth); thus, Huang teaches the membrane targeting amino acid sequence is joined in-frame to the C-terminus of the NF1-GRD (FIG. 7A-C, pg. 2428).
Regarding claim 67, Huang teaches a pharmaceutical composition comprising a recombinant nucleic acid comprising a nucleotide sequence encoding a polypeptide comprising a NF1-GRD and a KRas membrane targeting amino acid sequence (FIG. 7B-C, pg. 2428, showing growth inhibition of NIH 3T3 cells administered the NF1GRRA or NF1GRRK constructs; wherein the construct s were administered in a “calcium phosphate” transfection composition; see also “NIH 3T3 transfections”, pg. 2422, left col.).
As described above, Huang does not teach I) the sequence of the NF1-GRD, II) that the recombinant polypeptide consists of an NF1-GRD and KRas membrane targeting sequence, or II) that the KRas membrane targeting amino acid sequence is SEQ ID NO: 16. The obviousness of substituting Huang’s NF1-GRD for an NF1-GRD encompassing the minimal domain taught by Ahmadian, selected from a range of known residues of NF1 is described above in paragraph 10 and applied here. The obviousness of fusing the NF1-GRD directly to the KRas membrane targeting sequence (i.e., removing the myc tag of Huang) is described above in paragraph 12 and applied here. The obviousness of substituting the KRas membrane targeting sequence taught by Huang for SEQ ID NO: 16 is described above in paragraph 14 and applied here.
Regarding claim 68, Huang teaches the recombinant nucleic acid was cloned onto a NF1-GRD plasmid vector, ptrpNF1GRD (FIG. 7 description, pg. 2428; pg. 2421, right col.). Thus, the pharmaceutical composition taught by Huang comprises a gene-delivery vector comprising the recombinant nucleic acid.
Regarding claim 69, “therapeutically effective dose” is interpreted as a dose or amount of the composition determined to bring about a desired therapeutic effect, e.g., growth inhibition. Huang teaches administering the pharmaceutical composition at 20, 200, and 2000 ng of recombinant nucleic acid (Fig. 7B). Huang teaches that each dose of recombinant nucleic acid is “growth inhibitory to NIH 3T3 fibroblasts” (FIG. 7B and description, pg. 2428). Because Huang demonstrates amounts of the composition which bring about a desired therapeutic effect, i.e., growth inhibition, Huang teaches the pharmaceutical composition provided in a therapeutically effective dose.
Regarding claim 71, Walker teaches that gene therapy for NF1 would use a recombinant adeno-associated virus (rAAV) containing an expression cassette encoding neurofibromin, that replaces mutant alleles and thereby restores neurofibromin levels and function (pg. 427, left col.). As described above, Walker teaches employing “a truncated version of the NF1 gene retaining an appropriate level of function” (“5.1.3. Gene therapy”, pg. 427). Walker teaches that delivery of a truncated NF1 gene would circumvent the need to increase cargo capacities of available vectors or develop novel delivery systems, which would otherwise be required to deliver the large, full-length NF1 cDNA (“5.1.3. Gene therapy”, pg. 427).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have formulated the recombinant nucleic acid rendered obvious above in paragraph 17 in a gene-delivery virus in view of Walker. It would have amounted to a simple substitution of two known techniques to deliver nucleic acids (a plasmid vector taught by Huang and a viral vector taught by Walker), by known means, to yield predictable results. A skilled artisan would have had a reasonable expectation of success in formulating the recombinant nucleic acid in a gene-delivery virus rather than a gene-delivery plasmid vector taught by Huang, because as evidenced by Walker, a gene-delivery virus is a suitable means to express and deliver neurofibromin. Plasmid vectors and viral vectors are art-recognized equivalents for the purpose of delivering nucleic acids to cells. Indeed, the specification states that “Foreign nucleic acids… may be introduced into a cell using any method known to those skilled in the art… Such methods include transfection, transduction, viral transduction… transformation.” Accordingly, “An express suggestion to substitute one equivalent component or process for another is not necessary to render such substitution obvious. In re Fout, 675 F.2d 297, 213 USPQ 532 (CCPA 1982).” See MPEP 2144.06(II).
Regarding claim 72, “formulated in one or more unit doses” is interpreted as requiring that the composition be formulated in a predetermined quantity, optionally in association with a carrier, which, when administered in one or more doses, produces a desired effect (specification, pg. 17, line 33 to pg. 18, line 8). Huang teaches administering the pharmaceutical composition at 20, 200, and 2000 ng of recombinant nucleic acid (Fig. 7B). Huang teaches that each dose of recombinant nucleic acid is “growth inhibitory to NIH 3T3 fibroblasts” (FIG. 7B and description, pg. 2428). Because Huang demonstrates predetermined quantities of the composition which bring about a desired therapeutic effect, i.e., growth inhibition, Huang teaches the pharmaceutical composition formulated in one or more unit doses.
Claim 73 is rejected over Huang, Ahmadian, GenPept, Walker, Cox, and Laporte as applied to claim 67 above, further as evidenced by Qiu (Qiu et al., 2022, Materials Today Bio, 17, p. 1-21; of record).
Regarding claim 73, Huang teaches a pharmaceutical composition comprising the recombinant nucleic acid in calcium phosphate (FIG. 7B, pg. 2428; “NIH 3T3 transfections”, pg. 2422). Huang is silent as to whether the composition is formulated for administration with a second medical intervention that is a drug. However, Qiu teaches calcium phosphate compositions are formulated to administer second medical interventions, e.g., other nucleic acids, drugs, by virtue of the interactions between the calcium ions and functional groups of the drug molecules (Qiu, Fig. 3, pg. 5). Therefore, as evidenced by Qui, the pharmaceutical composition of Huang is inherently formulated for administration with a second medical intervention that is a drug.
Claims 74-76 are rejected over Huang, Ahmadian, GenPept, Walker, Cox, and Laporte as applied to claim 67 above, further as evidenced by Sokolova (Sokolova and Epple, 2021, Chemistry – A European Journal, 27, pg. 7471-7488; of record).
Regarding claims 74-76, as stated above, Huang teaches a pharmaceutical composition comprising the recombinant nucleic acid in calcium phosphate (FIG. 7B, pg. 2428; “NIH 3T3 transfections”, pg. 2422). Huang is silent as to whether the composition is formulated for intravenous administration (claim 74), systemic administration (claim 75), or local administration to a targeted tissue (claim 76). However, Sokolova teaches that calcium phosphate compositions are suitable for intravenous injection, which leads to systemic administration (“pronounced distribution in the body”, pg. 7483, right col.). Sokolova also teaches that such compositions are suitable for direct injection to a targeted tissue (“attractive option for a local drug delivery”, pg. 7484). Therefore, as evidenced by Sokolova, the pharmaceutical composition of Huang is inherently formulated for intravenous administration (claim 74), systemic administration (claim 75), and local administration to a targeted tissue (claim 76).
Response to Remarks - 35 USC § 103
Applicant’s arguments with respect to the § 103 rejections raised in the prior action have been considered. Applicant submits that the cited prior art fails to teach or suggest all the features of the amended claims. Specifically, Applicant indicates that “No art of record teaches a membrane targeting amino acid sequence from KRas4A such as KRas4A-C22 (SEQ ID NO: 16).” As stated above, Examiner agrees with this conclusion, and the previous § 103 rejections have been withdrawn. Applicant’s arguments are moot because the new grounds of rejection do not rely on any reference applied in the prior rejection of record for any teaching or matter specifically challenged in the argument.
Conclusion
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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/JENNA L PERSONS/Examiner, Art Unit 1637
/Soren Harward/Primary Examiner, TC 1600