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 .
DETAILED ACTION
RESPONSE TO AMENDMENT
Status of Application/Amendments/claims
2. Applicant’s amendment filed April 7, 2026 is acknowledged. Claims 1-35, 37, 40-49, 51-52 and 56 are canceled. Claims 36, 38-39, 50, 53-55 and 57-59 are amended. Claims 36, 38-39, 50, 53-55 and 57-59 are pending in this application. Election was treated as without traverse in the reply filed on September 15, 2025.
3. Claims 36, 38-39, 50, 53-55 and 57-59 are under examination in this office action.
4. Applicant’s arguments filed on April 7, 2026 have been fully considered but they are not deemed to be persuasive for the reasons set forth below.
Specification
5. The specification stands objected to because the use of the tradename or a trademark “nanobody” is not accompanied by the generic terminology and not capitalized.
On p. 5 of the response, Applicant argues that the objection to the specification due to the use of tradename or mark “nanobody” is improper because the cited portion of the specification is an art-recognized definition of “nanobody”.
Applicant’s arguments have been fully considered but they are not found persuasive. Contrary to Applicant’s arguments, the examiner asserts that the term “nanobody” (p.34, [0094]-p. 35, [0095]) is a trade name or a trademark used in commerce. The use of the trade name or trademark should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term. Appropriate correction is required.
Claim Rejections/Objections Withdrawn
6. The rejection of claims 37, 40-49, 51-52 and 56 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 is moot because the claims are canceled.
The rejection of claims 36-59 under 35 U.S.C. 102(a)(1) as being anticipated by Pei’648 (WO2018089648) is withdrawn in response to Applicant’s amendment to the claims and cancelation of claims 37, 40-49, 51-52 and 56
The rejection of claims 36-44, 46, 48-51 and 53-59 under 35 U.S.C. 102(a)(1) as being anticipated by Pei’691(WO2015/179691) is withdrawn in response to Applicant’s amendment to the claims and cancelation of claims 37, 40-49, 51-52 and 56.
The rejection of claims 45, 47 and 51-52 under 35 U.S.C. 103 as being unpatentable over Pei’648 (WO2018089648) in view of Gait et al. (WO2015022504) is moot because the claims are canceled.
The rejection of claims 36-59 on the ground of nonstatutory double patenting as being unpatentable over claims 6-7, 10-12, 17-22 of US10626147, claims 16-27, 36-40 of US10815276, claims 8-20, 23-34 and 41 of US11225506, or claims 1-4, 12-18 of US11878046 is withdrawn in response to Applicant’s amendment to the claims and cancelation of claims 37, 40-49, 51-52 and 56.
The provisional rejection of claims 36-59 on the ground of nonstatutory double patenting as being unpatentable over claims 1, 2, 6 and 50-52 of copending Application No. 18/278259 or claims 1 and 5-20 of copending Application No. 18/734759 is withdrawn in response to Applicant’s amendment to the claims and cancelation of claims 37, 40-49, 51-52 and 56.
Claim Rejections/Objections Maintained
In view of the amendment filed on April 7, 2026, the following rejections are maintained.
Claim Rejections - 35 USC § 112
7. 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 36, 38-39, 50, 53-55 and 57-59 stand 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 pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention. The rejection is maintained for the reasons of record and the reasons set forth below.
Claims 36, 38-39, 50, 53-55 and 57-59 as amended are directed to a modified looped protein comprising one or more surface loops and at least one cell penetrating peptide (CPP) motif comprising 6-8 amino acids inserted into the one or more surface loops, wherein the CPP motif comprises WWWRRRR (SEQ ID NO:117), RRRRWWW(SEQ ID NO:118), WWWRRR (SEQ ID NO:123) or RRRWWW (SEQ ID NO:124), wherein each W may be independently replaced with phenylalanine (F or f) or tyrosine (Y or y).
Claims 36, 38-39, 50, 53-55 and 57-59 encompass a genus of structurally and functionally undefined modified looped protein comprising a genus of one or more structurally and functionally undefined surface loops and at least one recited CPP motif inserted in the genus of one or more structurally and functionally undefined surface loops.
Claim 53 encompasses a genus of structurally and functionally undefined modified looped protein having a genus of structurally and functionally undefined loop comprising a genus of beta turn or a genus of omega loop.
Claim 54 encompasses a genus of structurally and functionally undefined modified looped protein having a genus of structurally and functionally undefined loop that is not an alpha-helix or beta-strand beta.
Claim 55 encompasses a genus of structurally and functionally undefined modified looped protein having a genus of structurally and functionally undefined loop comprising a genus of structurally and functionally undefined less than 200 amino acids.
Claim 57 encompasses a genus of structurally and functionally undefined modified looped protein having a genus of structurally and functionally undefined loop comprising a genus of structurally and functionally undefined CDR of a genus of structurally and functionally undefined antibody.
Claim 58 encompasses a genus of structurally and functionally undefined modified looped protein having a CCP inserted between a genus of structurally and functionally undefined amino acids in a genus of structurally and functionally undefined loop region of the genus of structurally and functionally undefined protein without removing or replacing a genus of structurally and functionally undefined amino acids in the genus of structurally and functionally undefined protein.
Claim 59 encompasses a genus of structurally and functionally undefined modified looped protein comprising a genus of structurally and functionally undefined enzyme, a genus of structurally and functionally undefined antibody or antigen-binding fragment thereof, a genus of structurally and functionally undefined transmembrane protein, a genus of structurally and functionally undefined protein tyrosine phosphatase, a genus of structurally and functionally undefined glycosyltransferase, a genus of structurally and functionally undefined fluorescent protein.
Applicant has not disclosed sufficient species for the broad genus of modified looped protein:
i) comprising one or more surface loops and at least one CPP motif comprising 6-8 amino acids inserted into the one or more surface loops, wherein the CPP motif comprises WWWRRRR (SEQ ID NO:117), RRRRWWW(SEQ ID NO:118), WWWRRR (SEQ ID NO:123) or RRRWWW (SEQ ID NO:124), wherein each W may be independently replaced with phenylalanine (F or f) or tyrosine (Y or y);
ii) having a genus of structurally and functionally undefined loop comprising a beta turn or an omega loop;
iii) having a genus of structurally and functionally undefined loop that is not an alpha-helix or beta-strand beta;
iv) having a genus of structurally and functionally undefined loop comprising structurally and functionally undefined less than 200 amino acids;
v) having a genus of structurally and functionally undefined loop comprising a genus of structurally and functionally undefined CDR of a genus of structurally and functionally undefined antibody;
vi) having a CCP inserted between a genus of structurally and functionally undefined amino acids in the genus of structurally and functionally undefined loop region of the genus of structurally and functionally undefined protein without removing or replacing a genus of structurally and functionally undefined amino acids in the genus of structurally and functionally undefined protein;
vii) comprising a genus of structurally and functionally undefined enzyme, a genus of structurally and functionally undefined antibody or antigen-binding fragment thereof, a genus of structurally and functionally undefined transmembrane protein, a genus of structurally and functionally undefined protein tyrosine phosphatase, a genus of structurally and functionally undefined glycosyltransferase or a genus of structurally and functionally undefined fluorescent protein.
Response to Arguments
On p. 6-7 of the response, Applicant argues that: i) Applicant is in possession of the claimed genus of modified looped protein in view of amendment to the claims by reciting specific CPP of SEQ ID NOs: 117, 118, 123 and 124; ii) The specification provides support for the claimed genus of CPP and the claimed genus of modified looped proteins ,and cites para. [0131], [0149]-[0151], Example 5 in support of the arguments; and iii) The specification provides support for inserting CPPs into one or more surface loops, or a CDR loop in an antibody or antigen-binding fragment and cites para. [0069]; [0096], [0031] and [0049] in support of the arguments.
Applicant's arguments have been fully considered but they are not found persuasive. Contrary to Applicant's arguments, the examiner asserts that based on MPEP §2163, MPEP §§2163.01-2163.03, the specification fails to provide sufficient description or information or evidence to demonstrate that Applicant is in possession of the claimed genus of structurally and functionally undefined modified looped proteins i)-vii) recited in the claims as set forth above because:
i. There is no well-established structural and functional relationship or correlation between the claimed genus of structurally and functionally undefined modified looped proteins i)-vi) recited in the claims and specific loop insertion mutants of PTP1B-1W (SEQ ID NO:136), PTP1B-2R (SEQ ID NO:139) and PTP1B-4R (SEQ ID NO:143); GBN-3W (SEQ ID NO:165); EGFP-R3W3 (SEQ ID NO:169) or EGFP-R4W4 (SEQ ID NO:170); and PNP-3R (SEQ ID NO:175) shown in Examples 1-6 and Figures 4A-B, 7-8, 11-1 and 14B and Tables 5A and 6).
ii. Based on Applicant’s own admission in the specification (para. [0151]), the stability of mutant proteins with insertion of amphipathic CPP sequences into protein loops depends on the specific CPP sequences, the site of insertion and the nature of the host protein.
The specification only describes loop insertion mutants with a CPP (SEQ ID NO:117 or 118) in a specific loop region of PTP1B, GFP-binding Nanobody (GBN), EGFP and Purine Nucleoside Phosphorylase (PNP). The specification fails to provides a well established structural and functional relationship or correlation between the claimed modified looped proteins and PTP1B, GFP-binding Nanobody (GBN), EGFP and Purine Nucleoside Phosphorylase (PNP) or loop insertion mutants with a CPP of SEQ ID NO:117 or 118 or 123 or 144 in a specific loop region of PTP1B, GBN, EGFP or PNP.
Based on Applicant’s own admission in the specification (Examples 1-7), only PTP1B-1W (SEQ ID NO:136), PTP1B-2R (SEQ ID NO:139) and PTP1B-4R (SEQ ID NO:143); GBN-3W (SEQ ID NO:165); EGFP-R3W3 (SEQ ID NO:169) and EGFP-R4W4 (SEQ ID NO:170); and PNP-3R (SEQ ID NO:175) can still maintain the activities of the proteins.
Based on Applicant’s own admission, only the following specific loop insertion mutants with a CPP (SEQ ID NO:117 or 118) in a specific loop region of PTP1B, GFP-binding Nanobody (GBN), EGFP and Purine Nucleoside Phosphorylase (PNP) can still maintain activities:
1. PTP1B with the CPP of SEQ ID NO:117 or 118 in 5 solvent exposed loop regions of PTP1B (Examples 1-2, Figures 4A-B):
i) only PTP1B-1W (SEQ ID NO:136), PTP1B-2R (SEQ ID NO:139) and PTP1B-4R (SEQ ID NO:143) among the 10 loop insertion mutants of PTP1B in Table 1 showed catalytic activities as wild type PTP1B based on p-nitrophenyl phosphate (pNPP, 0.5mM) as substrate; and
ii) only PTP1B-2R (SEQ ID NO:139) and PTP1B-4R (SEQ ID NO:143) mutants exhibited lower pY level in NIH 3T3 cells.
2. GFP-binding Nanobody (GBN) with the CPP of SEQ ID NO:117 or 118 in Non-CDR loops and CDR1-3 of GBN (Examples 3-4, Tables 3-5, Figures 7-8, 11-12):
i) only GBN-1W (SEQ ID NO:161), GBN-3W (SEQ ID NO:165) and GBN-3R (SEQ ID NO:164) produced soluble proteins;
ii) only GBN-3W (SEQ ID NO:165) and GBN-3R (SEQ ID NO:164) can form a complex with GFP at 1:1;
iii) GBN-3R failed to co-localize with intracellularly expressed GFP in HeLa cells;
iv) only GBN-3W showed partially colocalize with GFP; and
v) GBN-3W-NLS (c-Myc nuclear localization signal) failed to cause nuclear accumulation of GFP or colocalize with GFP.
3. EGFP with the CPP of SEQ ID NO:117 or 118 in Loop 9 of EGFP (Example 5, Table 5A):
i) EGFP- W3R3(SEQ ID NO:168) showed no improvement in cellular uptake compared to WT EGFP; and
ii) only EGFP-R3W3 (SEQ ID NO:169) and EGFP-R4W4 (SEQ ID NO:170) entered the cell with 8 and 13-fold higher efficiency than EGFP.
4. Purine Nucleoside Phosphorylase (PNP) with the CPP of SEQ ID NO:117 or 118 in loop regions of His20-Pro25 (loop 1), Asn74-Gly75 (loop 2) and Gly182-Leu187 (loop 3) of PNP (Example 6, Table 6, Figure 14B):
i) Only PNP-3R (SEQ ID NO:175) resulted in 1.35-fold higher PNP activity than normal S49 cells based on a commercial PNP enzymatic assay kit.
The specification provides no structural and functional relationship and correlation between the claimed genus of modified looped proteins i)-vi) recited in the claims and the PTP1B-1W (SEQ ID NO:136), PTP1B-2R (SEQ ID NO:139) and PTP1B-4R (SEQ ID NO:143); GBN-3W (SEQ ID NO:165); EGFP-R3W3 (SEQ ID NO:169) and EGFP-R4W4 (SEQ ID NO:170); and PNP-3R (SEQ ID NO:175) that sill maintain activities of their counterparts as shown in Examples 1-6.
iii. The specification fails to teach what other modified looped proteins are. The specification fails to teach what other structures/amino acid sequences can or cannot be included/changed in the genus of modified looped proteins i)-vi) recited in the claims in order to preserve the activity of the claimed genus of structurally and functionally undefined modified looped proteins i)-vi) set forth above or the activity of PTP1B-1W (SEQ ID NO:136), PTP1B-2R (SEQ ID NO:139) and PTP1B-4R (SEQ ID NO:143); GBN-3W (SEQ ID NO:165); EGFP-R3W3 (SEQ ID NO:169) and EGFP-R4W4 (SEQ ID NO:170); and PNP-3R (SEQ ID NO:175).
The specification provides no identification of any particular portion of the structure that must be conserved for the claimed genus of modified looped proteins i)-vi) recited in the claims. The instant specification fails to provide sufficient descriptive information, such as definitive structural or functional features of the claimed genus of modified looped proteins i)-vi) recited in the claims as set forth above. There is no description of the conserved regions which are critical to the function of the claimed genus. There is no description of the sites at which variability may be tolerated and there is no information regarding the relation of the structure of other modified looped proteins i)-vi) set forth above to the function of PTP1B-1W (SEQ ID NO:136), PTP1B-2R (SEQ ID NO:139) and PTP1B-4R (SEQ ID NO:143); GBN-3W (SEQ ID NO:165); EGFP-R3W3 (SEQ ID NO:169) and EGFP-R4W4 (SEQ ID NO:170); and PNP-3R (SEQ ID NO:175) shown in Examples 1-6. Furthermore, the prior art does not provide compensatory structural or correlative teachings sufficient to enable one of skill to identify what other modified looped proteins i)-vi) recited in the claims as set forth above might be.
Since the common characteristics/features of other modified looped proteins i)-vi) set forth above are unknown, a skilled artisan cannot envision the functional correlations of the genus with the claimed invention in view of Burgess et al. (J of Cell Bio. 1990, 111:2129-2138, cited previously), Bowie et al. (see col 2, p. 1306, Bowie et al. Science, 1990, 247:1306-1310, cited previously), Pawson et al. (see p. 445 the second column, first paragraph, Pawson et al. 2003, Science 300:445-452, cited previously), Alaoui-lsmaili et al. (see p. 502, right col., 2th paragraph; Alaoui-lsmaili et al., Cytokine Growth Factor Rev. 2009; 20:501-507, cited previously) and Guo et al. (see p. 9207, left col., 2th paragraph, Guo et al., PNAS 2004; 101:9205-9210, cited previously).
Accordingly, in the absence of sufficient recitation of distinguishing identifying characteristics, the specification does not provide adequate written description of the genus of modified looped proteins i)-vi) recited in the claims as set forth above.
Based on MPEP § 2161.01 and §2163, “to satisfy the written description requirement, a patent specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention. See, e.g., Moba, B.V. v. Diamond Automation, Inc., 325 F.3d 1306, 1319, 66 USPQ2d 1429, 1438 (Fed. Cir. 2003); Vas-Cath, Inc. v. Mahurkar, 935 F.2d at 1563, 19 USPQ2d at 1116”.
Vas-Cath Inc. v. Mahurkar, 19USPQ2d 1111, clearly states “applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the ‘written description’ inquiry, whatever is now claimed.” (See page 1117.) The specification does not “clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed.” (See Vas-Cath at page 1116).
As discussed above, the skilled artisan cannot envision the detailed chemical structure of the encompassed genus of modified looped proteins i)-vi) recited in the claims as set forth above, and therefore conception is not achieved until reduction to practice has occurred, regardless of the complexity or simplicity of the method of isolation. Adequate written description requires more than a mere statement that it is part of the invention and reference to a potential method of isolating it. The compound itself is required. See Fiers v. Revel, 25 USPQ2d 1601 at 1606 (CAFC 1993) and Amgen Inc. v. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016. One cannot describe what one has not conceived. See Fiddes v. Baird, 30 USPQ2d 1481 at 1483 and Centocor v. Abbott, 636 F.3d1341 (Fed. Cir. 2011) and AbbVie v. Janssen, 759 F.3d 1285 (Fed. Cir.2014). One cannot describe what one has not conceived. See Fiddes v. Baird, 30 USPQ2d 1481 at 1483.
Therefore, the claimed modified looped proteins i)-vi) recited in the claims have not met the written description provision of 35 U.S.C. §112, first paragraph. Applicant is reminded that Vas-Cath makes clear that the written description provision of 35 U.S.C. §112 is severable from its enablement provision (see page 1115). Applicant is directed to the Guidelines for the Examination of Patent Applications Under the 35 U.S.C. 112, ¶ 1 "Written Description" Requirement. See MPEP § 2161.01 and 2163.
Accordingly, the rejection of claims 36, 38-39, 50, 53-55 and 57-59 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 is maintained.
Double Patenting
8. 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 36, 38-39, 50, 53-55 and 57-59 stand provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-22 of copending Application No.18/847105 (the ‘105 Application), or claims 1-5, 9-15, 17-19 and 22-26 of copending Application No.18/862643 (the ‘643 Application). The rejection is maintained for the reasons of record and the reasons set forth below.
Response to Arguments
On p. 8-9 of the response, Applicant requests to hold the rejection in abeyance until allowable claims are indicated, and then Applicant will address any remaining double patenting rejections.
In response, the provisional rejection of claims 36, 38-39, 50, 53-55 and 57-59 on the ground of nonstatutory double patenting as being unpatentable over claims 1-22 of copending Application No.18/847105, or claims 1-5, 9-15, 17-19 and 22-26 of copending Application No.18/862643 is maintained of record until a terminal disclaimer is filed. (the ‘643 Application).
In this case, the peptide recited in claims 1-22 of the ‘105 Application or claims 1-5, 9-15, 17-19 and 22-26 of the ‘643 Application comprising a membrane translocation domain having at least one or more CPP motifs, wherein the at least one or more CPP motif is 3-10 or 2-8 amino acid residue in length and has at least two hydrophobic residues and wherein the transmembrane domain includes human fibronectin type III having BC, DE, CD and FG loops and one or more of the BC, DE, CD and FG loops have CPP motifs, and wherein the CPP motifs include RRRWWW or WWWRRR, which meets the claimed modified looped protein recited in instant claims and thus anticipates instant claims.
Accordingly, the provisional rejection of claims 36, 38-39, 50, 53-55 and 57-59 on the ground of nonstatutory double patenting as being unpatentable over claims 1-22 of copending Application No.18/847105, or claims 1-5, 9-15, 17-19 and 22-26 of copending Application No.18/862643 is maintained.
New Grounds of Rejection Necessitated by the Amendment
The following rejections are new grounds of rejections necessitated by the amendment filed on April 7, 2026.
Claim Rejections - 35 USC § 112
9. The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 36, 38-39, 50, 53-55 and 57-59 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 pre-AIA the applicant regards as the invention.
Claims 36, 38-39, 50, 53-55 and 57-59 are indefinite because:
i. Claim 36 recites the limitation “wherein each W may be independently replaced with phenylalanine (F or f) or tyrosine (Y or y)“. It is unclear what scope Applicant intended to include in the claims and whether each W in recited SEQ ID NOs: is replaced with phenylalanine (F or f) or tyrosine (Y or y), which renders the claim indefinite. The same issue applies to claims 38-39.
ii. Claims 38-39 recite both narrow and broad limitations. A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, claim 38 recites the broad recitation “wherein the CPP motif comprises at least three arginines and at least three tryptophans…”, and the claim also depends from claim 36 that recites “at least one CPP motif comprising 6-8 amino acids….wherein the CPP motif comprises the amino acid sequence….SEQ ID NO:117, ….SEQ ID NO:118, ….SEQ ID NO:123, or…..SEQ ID NO:124, wherein each W may be independently replaced with phenylalanine (F or f) or tyrosine (Y or y)…”, which is the narrower statement of the range/limitation. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
iii. The rest of claims are indefinite as depending from an indefinite claim.
Claim Rejections - 35 USC § 112
10. 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 35 U.S.C. 112 (pre-AIA ), fourth paragraph:
Subject to the [fifth paragraph of 35 U.S.C. 112 (pre-AIA )], 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.
Claims 38-39 are ejected 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. Claims 38-39 recite “wherein the CPP motif comprises at least three arginines and at least three tryptophans…”. But Claims 38-39 also depend from claim 36 which recites “at least one CPP motif comprising 6-8 amino acids….wherein the CPP motif comprises the amino acid sequence….SEQ ID NO:117, ….SEQ ID NO:118, ….SEQ ID NO:123, or…..SEQ ID NO:124, wherein each W may be independently replaced with phenylalanine (F or f) or tyrosine (Y or y)…”, which is the narrower limitation. Thus, claims 38-39 are of improper dependent form for failing to further limit the subject matter of the claim upon which it depends. 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 § 102
11. The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 36, 38-39, 50, 53-55 and 57-59 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Chen (PhD Dissertation: Intracellular Protein Delivery by Genetically Encoded And Structurally constrained Cell-Penetrating peptides, 2019, Graduate Program in Chemistry, The Ohio State University, cited previously)
Claims 36, 38-39, 50, 53-55 and 57-59 as amended are drawn to a modified looped protein comprising one or more surface loops and at least one cell penetrating peptide (CPP) motif comprising 6-8 amino acids inserted into the one or more surface loops, wherein the CPP motif comprises WWWRRRR (SEQ ID NO:117), RRRRWWW(SEQ ID NO:118), WWWRRR (SEQ ID NO:123) or RRRWWW (SEQ ID NO:124), wherein each W may be independently replaced with phenylalanine (F or f) or tyrosine (Y or y).
Chen teaches modified looped proteins comprising one or more surface loops and at least one CPP motif comprising 6-8 amino acids inserted into the one or more surface loops (p. 23, table 2), wherein the modified looped proteins include modified EGFP mutants (p. 27-30, table 5 and p. 63, table 7), modified Purine nucleoside phosphorylase (PNP) mutants (p. 32-34, table 5) or modified GFP-binding nanobody (GBN) mutants (p. 69-73, Tables 8-9; p. 90, table 11); and wherein the CPP comprises WWWRRRR (W3R4: SEQ ID NO:117), RRRRWWW (R4W3: SEQ ID NO:118), WWWRRR (W3R3: SEQ ID NO:123) or RRRWWW(R3W3: SEQ ID NO: 124) (see p. 23 p. 27-38, tables 3-4; p.32, table 5; p. 69-73, tables 8-9), which meets the limitations recited in claims 36, 38-39, 50, 53-55 and 57-59.
Chen teaches that the modified EGFP mutants comprise a CPP inserted into a surface exposed loop of EGFP (p. 25-27; p. 28-31), include EGFP-W3R3, EGFP-R3W3, EGFP-R4W3 (p. 28, table 3; p. 42-43). The modified EGFP mutants comprise at least one loop comprising a beta-turn or an omega loop or not an alpha-helix or beta-strand as in claims 53-54 (see p.28) and comprise loop 9, i.e. amino acids 171-176, which are less than 200 amino acids as in claim 55 (see p. 28, table 3). The modified EGFP mutant: EGFPW3R3 comprises the at least one CPP that is inserted between amino acids in the loop region without removing or replacing amino acids of the EGFP as in claims 58-59 (see p. 28, table 3).
Chen teaches that the modified PNP mutants comprise a CPP inserted into the surface loop of His20-Pro25, Asn74-Gly75, and Gly182-Leu187 of the PNP and include PNP-W3R3, PNP-R3W3, PNP-R4W3 (p. 32-38, table 4; p. 44-46). The modified PNP mutants comprise a beta-turn or an omega loop or is not an alpha-helix or beta-strand as in claims 53-54 (see p.32-33, table 4) and comprises His20-Pro25, Asn74-Gly75, and Gly182-Leu187, which are less than 200 amino acids as in claim 55 (see p. 32).
Chen teaches that the modified GBN mutants comprise a CPP inserted into a surface exposed loop including non-CDR loops, CDR1 and CDR3 loops of GBN and include GBM-W3R3, GBN-R3W3, GBN-R4W3 (see p. 68-88, Table 9). The modified GBN mutants comprise non-CDR loops, CDR1 and CDR3 loops which comprises at least one loop comprising a beta-turn or an omega loop or not an alpha-helix or beta-strand as in claims 53-54 (see p.28), having amino acids 12-16, 40-45, 73-77 or 84-88, which are less than 200 amino acids as in claim 55 (see, p. 71, table 8). The modified GBN mutants comprise at least one loop comprising a CDR of an antibody as in claim 57 (see p. 69-73, tables 8-9) and the CPP is inserted between amino acids in the loop region without removing or replacing amino acids of the GBN as in claims 58-59 (see p. 60-93, tables 8-9). Thus, claims 36, 38-39, 50, 53-55 and 57-59 are r anticipated by Chen.
Claim Rejections - 35 USC § 103
12. 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 of this title, 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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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.
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 36, 38-39, 50, 53-55 and 57-59 are rejected under 35 U.S.C. 103 as being unpatentable over Chen (2019) in view of Pei’648 (WO2018089648, cited previously).
Chen is set forth above but fails to teach that wherein the CPP motif comprises WWWRRRR (SEQ ID NO:117), RRRRWWW(SEQ ID NO:118), WWWRRR (SEQ ID NO:123) or RRRWWW (SEQ ID NO:124), wherein each W is independently replaced with phenylalanine (F or f) or tyrosine (Y or y).
Pei’648 (WO2018089648) teaches compounds comprising bicyclic peptides having the formula of 1-12 (see p. 50-51), wherein a first cyclic peptide comprises a CPP (Xm) and a second cyclic peptide comprises a cargo peptide sequence (Xn), wherein the Xm comprises 4 or more amino acids, and includes WWWRRRR (SEQ ID NO:143) or WWWRRR (SEQ ID NO:146), FFFRRRR (SEQ ID NO:109), FFFRRR (SEQ ID NO:120), FfFRrR (SEQ ID NO:132), fFfRrR (SEQ ID NO:134), FfFrRr (SEQ ID NO:135), fFFФrRr (SEQ ID NO:136), fФfrRr (SEQ ID NO:137), ФFfrRr (SEQ ID NO:138) (i.e. W=tryptophan; R=L-arginine; r=D-arginine Ф=naphthylalanine; F=L-phenylalanine; f=D-phenylalanine) (See the sequence alignment below; p. 60-62, Table 2; p. 64-68). Pei’648 also teaches that tryptophan (W) can be replaced by tyrosine (Y or y) (see p. 63, table 3) (The CPP motif comprising FFFRRRR (SEQ ID NO:109), FFFRRR (SEQ ID NO:120), FfFRrR (SEQ ID NO:132), fFfRrR (SEQ ID NO:134), FfFrRr (SEQ ID NO:135) meets the limitation “each W is independently replaced with phenylalanine (F or f)” recited in claims 36 and 38-39 or “one to six D amino acids” in claim 50.
A person of ordinary skill in the art would have recognized that selecting and applying the known CPP sequence comprising WWWRRRR (SEQ ID NO:117), RRRRWWW(SEQ ID NO:118), WWWRRR (SEQ ID NO:123) or RRRWWW (SEQ ID NO:124), wherein each W is independently replaced with phenylalanine (F or f) or tyrosine (Y or y) and the known technique disclosed by Pei’648 to the Chen’s modified looped proteins or compounds would have yielded the predictable result of generation of a modified looped protein comprising one or more surface loops and at least one cell penetrating peptide (CPP) motif comprising 6-8 amino acids inserted into the one or more surface loops, wherein the CPP motif comprises WWWRRRR (SEQ ID NO:117), RRRRWWW(SEQ ID NO:118), WWWRRR (SEQ ID NO:123) or RRRWWW (SEQ ID NO:124) and wherein each W is independently replaced with phenylalanine (F or f) or tyrosine (Y or y), and resulted in an improved product because the CPP sequence comprising WWWRRRR (SEQ ID NO:117), RRRRWWW(SEQ ID NO:118), WWWRRR (SEQ ID NO:123) or RRRWWW (SEQ ID NO:124) and wherein each W is independently replaced with phenylalanine (F or f) or tyrosine (Y or y) has been used for generation of a CPP-a cargo molecule conjugate to deliver the cargo molecule including therapeutic agents as taught by Pei’648.
Using the known CPP sequence comprising WWWRRRR (SEQ ID NO:117), RRRRWWW(SEQ ID NO:118), WWWRRR (SEQ ID NO:123) or RRRWWW (SEQ ID NO:124), wherein each W is independently replaced with phenylalanine (F or f) or tyrosine (Y or y) in the Chen’s modified looped proteins/compounds would generate the claimed modified looped protein comprising a loop and a CPP comprising 6-8 amino acids inserted into the one or more surface loops, wherein the CPP motif comprises WWWRRRR (SEQ ID NO:117), RRRRWWW(SEQ ID NO:118), WWWRRR (SEQ ID NO:123) or RRRWWW (SEQ ID NO:124) and wherein each W is independently replaced with phenylalanine (F or f) or tyrosine (Y or y), and expand application of the Chen’s modified looped proteins/compounds in pharmaceutical purposes for drug screening, diagnosis and for better cell penetration and delivery of therapeutic treatment.
Thus, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to select and apply the known CPP sequence comprising WWWRRRR (SEQ ID NO:117), RRRRWWW(SEQ ID NO:118), WWWRRR (SEQ ID NO:123) or RRRWWW (SEQ ID NO:124), wherein each W is independently replaced with phenylalanine (F or f) or tyrosine (Y or y) and the known technique disclosed by Pei’648 to the Chen’s modified looped proteins or compounds to provide better cell penetration and delivery of therapeutic treatment or diagnosis, and yield the predictable result of generation of a modified looped protein comprising one or more surface loops and at least one cell penetrating peptide (CPP) motif comprising 6-8 amino acids inserted into the one or more surface loops, wherein the CPP motif comprises WWWRRRR (SEQ ID NO:117), RRRRWWW(SEQ ID NO:118), WWWRRR (SEQ ID NO:123) or RRRWWW (SEQ ID NO:124) and wherein each W is independently replaced with phenylalanine (F or f) or tyrosine (Y or y).
The sequence search results disclose as follows:
SEQ ID NO:136/SEQ ID NO:117/SEQ ID NO:123
BFH28580
(NOTE: this sequence has 4 duplicates in the database searched.
See complete list at the end of this report)
ID BFH28580 standard; peptide; 7 AA.
XX
AC BFH28580;
XX
DT 12-JUL-2018 (first entry)
XX
DE Bicyclic peptide constructing cell penetrating peptide, SEQ ID 143.
XX
KW antiinflammatory; autoimmune disease; cytostatic; drug delivery;
KW immunosuppressive; inflammatory disease; neoplasm;
KW prophylactic to disease; protein production; protein therapy;
KW therapeutic.
XX
OS Unidentified.
XX
CC PN WO2018089648-A2.
XX
CC PD 17-MAY-2018.
XX
CC PF 09-NOV-2017; 2017WO-US060881.
XX
PR 09-NOV-2016; 2016US-0419781P.
PR 22-NOV-2016; 2016US-0425550P.
PR 22-DEC-2016; 2016US-0438141P.
XX
CC PA (OHIO-) OHIO STATE INNOVATION FOUND.
XX
CC PI Pei D, Qian Z;
XX
DR WPI; 2018-38796M/42.
XX
CC PT New bicyclic peptide, for preparing pharmaceutical composition for
CC PT treating inflammatory disorder, autoimmune disorder, or disorder of
CC PT uncontrolled cellular proliferation; and for delivering therapeutic agent
CC PT to cytoplasm of cell.
XX
CC PS Claim 7; SEQ ID NO 143; 166pp; English.
XX
CC The present invention relates to a novel bicyclic peptide, useful in
CC preparing a pharmaceutical composition for treating inflammatory
CC disorder, autoimmune disorder or disorder of uncontrolled cellular
CC proliferation. The invention also provides: a pharmaceutical composition
CC comprising the bicyclic peptide and a pharmaceutical carrier; a method
CC for treating the inflammatory disorder, autoimmune disorder or disorder
CC of uncontrolled cellular proliferation by administering the bicyclic
CC peptide to a subject identified as having a need for treatment of the
CC disorder; a method for making the bicyclic peptide; and a method for
CC delivering a therapeutic agent to cytoplasm of a cell. The present
CC sequence represents a cell penetrating peptide sequence, which is used in
CC constructing the bicyclic peptide involved in preparing the
CC pharmaceutical composition for treating the above mentioned diseases.
XX
SQ Sequence 7 AA;
Query Match 67.9%; Score 53; Length 7;
Best Local Similarity 100.0%;
Matches 7; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 3 WWWRRRR 9
|||||||
Db 1 WWWRRRR 7
Double Patenting
13. Claims 36, 38-39, 50, 53-55 and 57-59 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-13, 16 and 19-24 of copending Application No.19/590973, or Claims 1-17 and 19-21 of Application No.19/521585. Although the claims at issue are not identical, they are not patentably distinct from each other because the peptide comprising a polypeptide linked to a membrane translocation domain comprising at least one or more CPP motifs and wherein the membrane translocation domain comprising loops having the CPP motifs recited in claims of the Application No.19590973 and 19/521585 meets the limitations recited in instant claims and thus anticipates instant claims.
Claims 1-13, 16 and 19-24 of Application No.19590973 (the ‘973 Application) claim a peptide comprising a gene-editing polypeptide having at least 90% similarity to SEQ ID NO:141, 148-151 or 236-251 linked to a membrane translocation domain having one or more CPP motifs, wherein the at least one CPP motif is 3-10 amino acid residue in length and has at least three arginines and/or lysine residues and at least one other CPP motif is 2-8 amino acid residues in length and has at least two hydrophobic residues, and wherein the transmembrane domain includes human fibronectin type III having BC, DE, CD and FG loops and one or more of the BC, DE, CD and FG loops have CPP motifs, and wherein the CPP motifs include RRRWWW or WWWRRR, which meets the claimed modified looped protein recited in instant claims. The claims of the ‘973 Application are a species of instant claims and thus anticipate instant claims.
Claims 1-17 and 19-21 of Application No.19/521585 (the ‘585 Application) claim a peptide comprising a Myc inhibitor polypeptide having at least 90% sequence similarity to SEQ ID NOs: 140-152 linked to a membrane translocation domain having at least one or more CPP motifs, wherein at least one CPP motif is 3-10 amino acid residue in length and has at least three arginines and/or lysine residues and at least one other CPP motif is 2-8 amino acid residues in length and has at least two hydrophobic residues, and wherein the transmembrane domain includes human fibronectin type III having BC, DE, CD and FG loops and one or more of the BC, DE, CD and FG loops have CPP motifs, and wherein the CPP motifs include RRRWWW or WWWRRR, which meets the claimed modified looped protein recited in instant claims.
Therefore, claims 36, 38-39, 50, 53-55 and 57-59 of instant Application are not patentably distinct from claims 1-13, 16 and 19-24 of the ‘973 Application, or claims 1-17 and 19-21 of the ‘585 Application because instant claims 36, 38-39, 50, 53-55 and 57-59 are anticipated by claims 1-13, 16 and 19-24 of the ‘973 Application, or claims 1-17 and 19-21 of the ‘585 Application.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
14. NO CLAIM IS ALLOWED.
Sequence alignment
SEQ ID NO:170 1 IRRRRWWWGSV 11
SEQ ID NO:143 1 PRRRRWWWHGP 11
SEQ ID NO:139 1 KRRRRWWWKE- 10
SEQ ID NO:118 1 -RRRRWWW--- 7
SEQ ID NO:124 1 –RRRWWW---- 6
15. The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
JP2005185101 teaches a transcription factor comprising -RRRRWWW (instant SEQ ID NO:118)- or -RRRWWW- (instant SEQ ID NO:124) (see the sequence alignment below).
SEQ ID NO:118: -RRRRWWW-
SEQ ID NO:124: -RRRWWW-
AQD45100
ID AQD45100 standard; protein; 98 AA.
XX
AC AQD45100;
XX
DT 12-JUN-2008 (first entry)
XX
DE Rice cDNA-encoded protein SEQ ID No 38959.
XX
KW plant; transgenic plant; crop improvement.
XX
OS Oryza sativa.
XX
CC PN JP2005185101-A.
XX
CC PD 14-JUL-2005.
XX
CC PF 11-DEC-2002; 2002JP-00383870.
XX
PR 30-MAY-2002; 2002JP-00203269.
XX
CC PA (DOKU-) DOKURITSU GYOSEI HOJIN NOGYO SEIBUTSU SH.
CC PA (SEIB-) SEIBUTSUKEI TOKUTEI SANGYO GIJUTSU.
CC PA (DOKU-) DOKURITSU GYOSEI HOJIN RIKAGAKU KENKYUSH.
CC PA (KOKU-) ZH KOKUSAI KAGAKU SHINKO ZAIDAN.
XX
CC PI Kikuchi H, Hayashizaki Y, Otomo Y, Matsubara K, Murakami K;
CC PI Kishimoto N, Sato K, Nagata T, Kawakami N, Yazaki J, Ishikawa M;
CC PI Doi K, Kawai J;
XX
DR WPI; 2005-566181/58.
XX
CC PT Novel DNA encoding transcription factor, derived from rice plant, useful
CC PT for obtaining transcriptional-regulatory regions in plant and for
CC PT producing modified plant.
XX
CC PS Claim 1; SEQ ID NO 38959; 2928pp; Japanese.
XX
CC The present invention relates to Rice cDNA clones and to: DNA encoding an
CC antisense RNA that is complementary to the transcription product of the
CC cDNA; a DNA encoding an RNA having ribozyme activity that cleaves
CC specifically the transcription product of the cDNA; DNA encoding an RNA
CC that suppresses the expression of cDNA through RNA interference effect at
CC the time of the expression in a plant cell; or a DNA encoding RNA that
CC suppresses the expression of the cDNA through co-suppression effect at
CC the time of expression in a plant cell; a vector containing the cDNA or
CC DNA encoding a interference RNA; a transformed plant cell the vector; a
CC transformed plant the plant cell; an offspring, a clone or a reproductive
CC fragment of the plant; a protein encoded by the cDNA; an antibody binding
CC to the protein encoded by the cDNA; a rice-genome database containing a
CC cDNA or protein sequence of the invention; and a method for determining
CC transcriptional-regulatory regions by mapping a base sequence chosen from
CC the cDNA sequences of the invention and determining the transcriptional-
CC regulatory region in the mapped region and in the 5'-terminal. The DNA
CC sequences, proteins, vectors, plants, antibodies, databases and methods
CC of the invention are useful for: producing the protein of the invention,
CC for producing transgenic plants, for controlling the expression of a gene
CC in a plant ,and for producing a modified plant with desired and different
CC characteristics. The present sequence is a protein encoded by a cDNA
CC clone of the invention.
XX
SQ Sequence 98 AA;
Query Match 83.8%; Score 57; Length 98;
Best Local Similarity 77.8%;
Matches 7; Conservative 2; Mismatches 0; Indels 0; Gaps 0;
Qy 1 KRRRRWWWK 9
:|||||||:
Db 80 RRRRRWWWR 88
WO2016187508 teaches a tumor-specific mutation containing human derived polypeptide comprising -WWWRRRR (instant SEQ ID NO:117)- or -WWWRRR- (instant SEQ ID NO:123) (see the sequence alignment below).
SEQ ID NO:117: -WWWRRRR-
SEQ ID NO:123: -WWWRRR-
BDJ76923
ID BDJ76923 standard; protein; 38 AA.
XX
AC BDJ76923;
XX
DT 12-JAN-2017 (first entry)
XX
DE Tumor-specific mutation containing human derived polypeptide, SEQ: 3102.
XX
KW cancer; chemotherapy; cytostatic; immune stimulation; immunotherapy;
KW mutein; prophylactic to disease; surgery; therapeutic;
KW vaccine, anticancer.
XX
OS Homo sapiens.
OS Synthetic.
XX
CC PN WO2016187508-A2.
XX
CC PD 24-NOV-2016.
XX
CC PF 20-MAY-2016; 2016WO-US033452.
XX
PR 20-MAY-2015; 2015US-0179877P.
PR 23-FEB-2016; 2016US-0389377P.
XX
CC PA (BROA-) BROAD INST INC.
CC PA (DAND ) DANA FARBER CANCER INST INC.
CC PA (GEHO ) GEN HOSPITAL CORP.
XX
CC PI Fritsch EF, Hacohen N, Rooney MS, Shukla SA;
XX
DR WPI; 2016-72379L/83.
XX
CC PT Pharmaceutical composition useful as immunogenic composition for
CC PT preventing or treating tumor, comprises neoantigenic peptide comprising
CC PT tumor-specific neoepitope capable of binding to human leukocyte antigen
CC PT (HLA) protein, and carrier.
XX
CC PS Example 4; SEQ ID NO 3102; 473pp; English.
XX
CC The invention relates to a novel pharmaceutical composition useful for
CC preventing or treating a tumor in a subject. The composition comprises at
CC least one neoantigenic peptide: (a) containing a tumor-specific mutation;
CC (b) containing a tumor-specific neoepitope capable of binding to a human
CC leukocyte antigen (HLA) protein in the subject; and (c) capable of
CC eliciting an immune response against a tumor. The pharmaceutical
CC composition herein is an immunogenic or a vaccine composition, used in
CC combination with an additional therapy for prophylactic cancer treatment.
CC The additional therapy is surgery, chemotherapy, or a targeted therapy.
CC The present sequence represents a human derived polypeptide comprising a
CC tumor-specific mutation, useful for preparing the pharmaceutical
CC composition.
XX
SQ Sequence 38 AA;
Query Match 69.2%; Score 54; Length 38;
Best Local Similarity 87.5%;
Matches 7; Conservative 1; Mismatches 0; Indels 0; Gaps 0;
Qy 2 QWWWRRRR 9
:|||||||
Db 23 RWWWRRRR 30
US2007214517 teaches a polypeptide from Arabidopsis, soybean, maize, wheat or rice comprising -WWWRRRR (instant SEQ ID NO:117)- or -WWWRRR- (instant SEQ ID NO:123) (see the sequence alignment below).
SEQ ID NO:117: -WWWRRRR-
SEQ ID NO:123: -WWWRRR-
ARN11445
(NOTE: this sequence has 1 duplicate in the database searched)
ID ARN11445 standard; protein; 150 AA.
XX
AC ARN11445;
XX
DT 07-AUG-2008 (first entry)
XX
DE Zea mays subsp. mays amino acid sequence SEQ ID 110816.
XX
KW plant; plant breeding; gene regulation; DNA detection; mapping.
XX
OS Zea mays subsp. mays.
XX
CC PN US2007214517-A1.
XX
CC PD 13-SEP-2007.
XX
CC PF 02-MAR-2007; 2007US-00713768.
XX
PR 13-FEB-2004; 2004US-0544190P.
PR 14-FEB-2005; 2005US-00056355.
XX
CC PA (CERE-) CERES INC.
XX
CC PI Alexandrov N, Brover V;
XX
DR WPI; 2008-B58774/11.
XX
CC PT New isolated nucleic acids and polypeptides from Arabidopsis, soybean,
CC PT maize, wheat, and rice, useful for controlling the behavior of a gene in
CC PT the chromosome, controlling the expression of a gene, or as tools for
CC PT genetic mapping.
XX
CC PS Claim 11; SEQ ID NO 110816; 122pp; English.
XX
CC The invention relates to an isolated nucleic acid molecule which
CC comprises (a) a full-length cDNA nucleic acid, or (b) a nucleic acid,
CC which is the reverse of the nucleotide sequence of (a), where the
CC sequences are described in the Sequence Listing which is available in
CC electronic form from the USPTO website. Also described: (1) a vector
CC construct comprising: (a) a first nucleic acid having a regulatory
CC sequence capable of causing transcription and/or translation; and (b) a
CC second nucleic acid having the sequence of the isolated nucleic acid
CC molecule above, where the first and second nucleic acids are operably
CC linked and where the second nucleic acid is heterologous to any element
CC in the vector construct; (2) a host cell comprising the isolated nucleic
CC acid molecule or the vector construct, where the nucleic acid molecule is
CC flanked by exogenous sequence; (3) an isolated polypeptide comprising an
CC amino acid sequence: (a) exhibiting at least 40-90% sequence identity of
CC an amino acid sequence encoded by a sequence in the Sequence Listing or
CC the Sequence Listing-Miscellaneous Feature documents, or a fragment; and
CC (b) capable of exhibiting at least one of the biological activities of
CC the polypeptide encoded by the nucleotide sequence in the Sequence
CC Listing or the Sequence Listing-Miscellaneous Feature documents, or a
CC fragment; (4) an antibody capable of binding the isolated polypeptide;
CC (5) a method of introducing an isolated nucleic acid into a host cell;
CC (6) a method for detecting a nucleic acid in a sample; (7) a plant or
CC cell of a plant comprising a nucleic acid molecule, which is exogenous or
CC heterologous to the plant or plant cell; (8) a plant or cell of a plant
CC comprising the vector construct; and (9) a plant, which has been
CC regenerated from a plant cell above. Specifically claimed are over 100000
CC isolated polynucleotides and their encoded polypeptides from Arabidopsis,
CC soybean, maize, wheat, and rice. The nucleic acids are useful for
CC specifying a gene product in cells, either as a promoter or as a protein
CC coding sequence or as an UTR or as a 3' termination sequence, and are
CC also useful in controlling the behavior of a gene in the chromosome, in
CC controlling the expression of a gene, or as tools for genetic mapping,
CC recognizing or isolating identical or related DNA fragments, or
CC identification of a particular individual organism, or for clustering of
CC a group of organisms with a common trait. The present sequence represents
CC a specifically claimed sequence-determined DNA fragment encoded amino
CC acid sequence from the present invention.
XX
SQ Sequence 150 AA;
Query Match 70.5%; Score 55; Length 150;
Best Local Similarity 88.9%;
Matches 8; Conservative 0; Mismatches 1; Indels 0; Gaps 0;
Qy 3 WWWRRRRND 11
||||||| |
Db 42 WWWRRRRWD 50
16. 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.
17. Any inquiry concerning this communication or earlier communications from the examiner should be directed to CHANG-YU WANG whose telephone number is (571)272-4521. The examiner can normally be reached Monday-Thursday, 7:00am-5:00pm EST.
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, Jeffrey Stucker can be reached at 571-272-0911. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
Chang-Yu Wang
June 23, 2026
/CHANG-YU WANG/Primary Examiner, Art Unit 1675
Prosecution Insights