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 21, 2026 is acknowledged. Claims 7-13, 16, 18-19, 27-28 and 30 are canceled. Claim 1 is amended. Claims 1-6, 14-15, 17, 20-26 and 29 are pending in this application. Claims 26 and 29 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to nonelected inventions, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on October 3, 2025.
3. Claims 1-6, 14-15, 17 and 20-25 are under examination with respect to SEQ ID NO: 19 in this office action.
4. Applicant’s arguments filed on April 21, 2026 have been fully considered but they are not deemed to be persuasive for the reasons set forth below.
Specification
5. The objection to the specification is withdrawn in response to Applicant’s amendment to the specification.
Claim Rejections/Objections Maintained
In view of the amendment filed on April 21, 2026, the following rejections are maintained.
Claim Rejections/Objections
6. Claims 2-4 are objected to because of the following informalities: the status of the claims 2-4 is incorrect because these claims are under examination. Appropriate correction is required.
See MPEP 714 & 37 CFR 1.121.
“In the claim listing, the status of every claim must be indicated after its claim number by using one of the following identifiers in a parenthetical expression: (Original), (Currently amended), (Canceled), (Withdrawn), (Previously presented), (New), and (Not entered).”
Claims 1 and 24 are objected to because of the following informalities: The limitation “a pharmaceutically acceptable salt, solvate, stereoisomer or prodrug thereof” recited in the last line of claim 1 is duplicate. The limitation “NMA” recited in the claim 24 is not a unique or common abbreviation in the art. Applicants are required to spell out “NMA” at the first usage. Appropriate correction is required.
Claim Rejections - 35 USC § 112
7. The following is a quotation 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 35 U.S.C. 112 (pre-AIA ), first paragraph:
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 1-6, 14-15, 17 and 20-25 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 1-6, 14-15, 17 and 20-25 as amended encompass a genus of compound of formula (I) or a pharmaceutically acceptable salt, solvate, stereoisomer or prodrug thereof, wherein R1, R2, X1-X11 have residues, structures and features recited in amended claim 1.
Applicant has not disclosed sufficient species for the broad genus of compound of formula (I) or pharmaceutically acceptable salt, solvate, stereoisomer or prodrug thereof as recited in amended claim 1. The specification fails to teach what other structures/amino acid sequences can or cannot be included/changed in the claimed compound of formula (I) in order to preserve the activity of SEQ ID NO: 4, 18, 19, 20 or 24 or SEQ ID NO:35 or to possess any specific activity of the compound of formula (I).
Response to Arguments
On p. 9-10 of the response, Applicant argues that i) the rejection has been overcome in view of amendment to claim 1 by incorporating lists of substituents for X1, X2 and X4 positions; ii) the specification provides support for the amendment and cites paragraphs [0008], [0054], [0066] and [0069]; iii) the claims do not recite any functional requirement such as KOR activity, EC50, lack of desensitization, signaling bias or analgesic efficacy; iv) the specification provides species of the compound of formula (I) (see para. [0072]), the detail structural definitions for recited residues including “non-proteinogenic amino acid” (para. [0025]), “hydrophilic, hydrophobic, positively charged, negatively charged and polar uncharged” (para. [0031]-[0035]), “tyrosine derivatives” (para. [0045]), 3-(4-pyridyl)-alanine derivatives (see para. [0050]) and phenylalanine derivative (see para. [0054]). Applicant further cites MPEP 2163 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 compound of formula (I) or pharmaceutically acceptable salt, solvate, stereoisomer or prodrug thereof having recited residues, structures and features because:
i. Based on Applicant’s own admission, a single amino acid substitution or difference on the claimed compound of formula (I) results in different activity or no activity in cAMP assay, for example SED ID NO:1, 9 or 10 (see table 4) or SEQ ID NO:16-17 (table 5).
ii. There is no well-established structural and functional relationship or correlation between the claimed genus of other compounds of formula (I) having residues, structures and features as recited in amended claim 1 and the peptide of SEQ ID NO:35 (CR845) or U50488H or the peptide of SEQ ID NOs: 4, 18, 19, 20 and 24.
There is no well-established structural and functional relationship or correlation between the claimed genus of compound of formula (I) as recited in amended claim 1 and the peptide of SEQ ID NOs: 4, 18, 19, 20 and 24 or CR845 (SEQ ID NO:35) or U50488H in a cAMP assay as shown in Examples 2-4, Table 4 and figures 2-3.
There is also no well-established structural and functional relationship or correlation between the claimed genus of compound of formula (I) and the peptide of SEQ ID NO:35 in desensitization or SEQ ID NO: 4, 18, 19 or 24 not causing KOR desensitization shown in Example 8 and figure 4, or no activity in pERK activity shown in Example 9 and figure 5, or SEQ ID NOs:19 and 24 in FCA model shown in Example 10 and figure 6 or even other activities.
The specification only describes: i) peptides of SEQ ID NOs: 2-4, 11-20, 24-25 and 28-31 having similar activity as positive controls (CR845, SEQ ID NO:35 and U50488H) based on a cAMP assay (see Examples 2-4, Table 4, Figures 2-3); ii) only SEQ ID NO:19 having close IC50 as U50488H but not SEQ ID NOs: 4, 20 or 24 (Table 7); iii) only SEQ ID NOs: 4, 18 and 19 not causing KOR desensitization (00112], Example 8, figure 4); iv) only SEQ ID NO:24 showing some influence over pEerk induction but not SEQ ID NOs: 4, 18 and 19 (Example 9, Figure 5); v) SEQ ID NOs: 4 and 19 showing better efficacy than U50488H, and SEQ ID NOs: 19 and 24 showing statistically significantly greater over morphine in FCA model (Example 10, figure 6).
The specification fails to provide sufficient species for the claimed genus of compound of formula (I) having residues, structures and features as recited in amended claim 1. The specification fails to teach what other structures/amino acid sequences can or cannot be included/changed in the claimed compounds of formula (I) in order to preserve the activity of SEQ ID NO:35 (CR845) or U50488H or SEQ ID NO: 4, 18, 19 or 24 in a cAMP assay, in KOR desensitization, in pERK activity, or in FCA model or even to have any specific activity or function.
Since the common characteristics/features of other compounds of formula (I) 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 compound of formula (I).
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 compound of formula (I), 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 compound of formula (I) has 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 1-6, 14-15, 17 and 20-25 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.
Claim Rejections - 35 USC § 102
8. 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 1-6, 14-15, 17, 20-23 and 25 stand rejected under 35 U.S.C. 102(a)(1) as being anticipated by Ambo et al. (Peptide Science-Present and Future; 1999, pp. 701-703, as in IDS). The rejection is maintained for the reasons of record and the reasons set forth below.
Claims 1-6, 14-15, 17, 20-23 and 25 as amended are drawn to a compound of formula (I), or a pharmaceutically acceptable salt, solvate, stereoisomer or prodrug thereof: R1NH-X1-X2-X3-X4-X5-X6-X7-X8-X9-X10-X11-C(O)R2 (I), wherein
R1 is hydrogen or C1-6akyl;
R2 is OH, NH2, NH(C1-6akyl) or N(C1-6alkyl);
X1 is L-tyrosine, phenylalanine, or L-3-(4-pyridyl)-alanine;
X2 is glycine, sarcosine, g4-aminobutyric acid, L/D-alanine, or L-D-3-(4-pyridyl)-alanine;
X3 is absent;
X4 is L/D-phenylalanine, or a phenylalanine derivative selected from L/D-4-nitrophenylalanine, L/D-4-Chlorophenylalanine, L/D-4-fluorophenylalanine;
X5 is glycine, L/D-leucine, L/D-isoleucine or L/D-valine;
X6 and X7 is a positively charged, a negatively charged or a polar uncharged amino acid residue;
X8 is absent, a hydrophobic amino acid residue or C1-10 alkylene;
X9 is absent or a positive charged or a polar uncharged amino acid residue;
X10 is absent or a hydrophobic acid;
X11 is absent or a positively charged amino acid residue; and
wherein at least one amino acid residue X1, X2 and X4-X7 is a non-proteinogenic amino acid; or a pharmaceutically acceptable salt, solvate, stereoisomer or prodrug thereof.
Response to Arguments
On p. 11-12 of the response, Applicant argues that i) X2 in amended claim 1 is limited to glycine, sarcosine, g-aminobutyric acid, L-alanine and L-3-(4-pyridyl)-alanine, which is outside the disclosure in Ambo and De Catiglione (should be De Castiglione); ii) peptides (2) and (9) disclosed by Ambo require D-alanine at position corresponding X2; iii) Ambo does not disclose glycine, sarcosine, g-aminobutyric acid, L-alanine and L-3-(4-pyridyl)-alanine as recited in amended claim 1 in place of D-alanine.
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 §2131, Ambo does teach the claimed compound of formula (I) having residues, structures and features as recited in claim 1 because:
i. “X2” recited in amended claim 1 does not exclude D-alanine because amended claim 1 recites “….X2 is selected from the group consisting of glycine, sarcosine, g4-aminobutyric acid, L-alanine, D-alanine and L-3-(4-pyridyl)-alanine…..”.
ii. The hybrid analogs of dermorphin-dynorphin including the peptide (2) and the peptide (9) disclosed by Ambo meet the limitations recited in instant claims 1-6, 14-15, 17, 20-23 and 25.
The peptide (2): “NH2-Y1A2F4L5R6R7I8-NH2” disclosed by Ambo mees the limitation recited in instant claim 1: R=hydrogen; X1=L-tyrosine (i.e. Y1); X2 =D-alanine (i.e. A2: a non-proteinogenic amino acid); X3=absent; X4=L-phenylalanine (i.e. F4); X5 =L-leucine (i.e. L5); X6= X7 =L-arginine (i.e. R6R7: a positively charged amino acid residue based on p. 10, para. [0031] of the specification filed 04/21/2026); X8 =L-isoleucine (i.e. I8: a hydrophobic amino acid residue based on p. 11, para. [0032] of the specification filed 04/21/2026); X9, X10, X11=absent; and R2=NH, and thus anticipates claims 1-6, 14-15, 17, 20-23 and 25.
The peptide (9): “NH2-Y1A2F4L5R6meR7-NHEt” disclosed by Ambo meets the limitations recited in instant claim 1: R1=hydrogen; X1=L-tyrosine (i.e. Y1); X2=D-alanine (i.e. A2: a non-proteinogenic amino acid); X3=absent; X4=L-phenylalanine (i.e. F4); X5=L-leucine (i.e. L5); X6=L-arginine (i.e. R6: a positively charged amino acid residue based on p. 10, para. [0031] of the present description); X7=N-methyl-L-arginine (i.e. meR7: a positively charged amino acid residue based on p. 10, para [0031] of the present description); X8, X9, X10, X11: absent; and R2=NH(C1-6alkyl) (i.e. ethyl), and thus anticipates claims 1-6, 14-15, 17, 20-23 and 25. Thus, claims 1-6, 14-15, 17, 20-23 and 25 are anticipated by Ambo.
Accordingly, the rejection of claims 1-6, 14-15, 17, 20-23 and 25 under 35 U.S.C. 102(a)(1) as being anticipated by Ambo is maintained.
Claim Rejections - 35 USC § 102
9. Claims 1-6, 20-23, and 25 stand rejected under 35 U.S.C. 102(a)(1) as being anticipated by De Castiglione (US4350627). The rejection is maintained for the reasons of record and the reasons set forth below.
Response to Arguments
On p. 12 of the response, Applicant argues that i) the compounds of claims 16, 24 and 74 disclosed in De Castiglione requires a D-alanine at position X2. However, X2 in amended claim 1 is limited to glycine, sarcosine, g-aminobutyric acid, L-alanine and L-3-(4-pyridyl)-alanine, which is not disclosed by De Castiglione.
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 §2131, De Castiglione (US4350627) does teach the claimed compound of formula (I) having residues, structures and features as recited in claim 1 because:
i. “X2” recited in amended claim 1 does not exclude D-alanine for the reasons set forth above.
ii. The peptide of formula I:
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having analgesic activity for the treatment of pain disclosed by De Castiglione meets the limitations recited in instant claim 1 (see abstract; col. 1, line 15- col. 2, line 16; col. 5, line 67-col.6, line 45; Col. 6-16, Examples 1-10, claims 16, 24, 74, 85 and 110).
The peptide derivative (29) disclosed by De Castiglione comprises “NH2-Tyr1-ala2-Phe4-Gly5-Tyr6-Ser7-NH2”, which meets the limitations: R: hydrogen; X1: L-tyrosine (i.e. Tyr1); X2: D-alanine (i.e. ala2: a non-proteinogenic amino acid based on p. para. [0024] of the specification filed 04/21/2026); X3: absent; X4: L-phenylalanine (i.e. Phe4); X5: glycine (i.e. Gly5); X6: L-tyrosine (i.e. Tyr6: a polar uncharged amino acid residue based on p. para. [0035] of the specification filed 04/21/2026); X7 = L-Serine (i.e. Ser7: a polar uncharged amino acid residue based on p. para. [0035] of the specification filed 04/21/2026); X8, X9, X10, X11: absent; and R2: NH recited in instant claim 1 (see col. 11, Example 5, lines46-47, and claim 16) and thus anticipates claims 1, 4-6, 20-23, and 25.
The peptide derivative recited in claim 24 disclosed by De Castiglione comprises “NH2-Tyr1-ala2-Phe4-Gly5-Tyr6-Gly7-Ser9-NH2”, which meets the limitations: R1: hydrogen; X1: L-tyrosine (i.e. Tyr1); X2: D-alanine (i.e. ala2: a non-proteinogenic amino acid per paragraph [0024] of the present description); X3: absent; X4: L-phenylalanine (i.e. Phe4); X5: glycine (i.e. Gly5); X6: L-tyrosine (i.e. Tyr6: a polar uncharged amino acid residue based on p. para [0034] of the specification filed 04/21/2026); X7 = glycine (i.e. Gly7: a polar uncharged amino acid residue based on p. para. [0034] of the specification filed 04/21/2026); X8: absent; X9:L-Serine (i.e. Ser9: a polar unchanged amino acid residue); X10= X11: absent; and R2: NH recited in instant claim 1, and thus anticipates claims 1, 4-8, 12, 20, 22, 23, and 25 (col. 21, claim 24).
The peptide derivative recited in claim 74 disclosed by De Castiglione comprises “H-Tyr1-ala2-Phe4-Gly5-Tyr6-Sar7-Ser9-NH2”, which meets the limitations: R: hydrogen; X1: L-tyrosine (Tyr1); X2: D-alanine (i.e. ala2: a non-proteinogenic amino acid); X3: absent; X4: L-phenylalanine (i.e. Phe4); X5: glycine (i.e. Gly5; X6: L-tyrosine (i.e. Tyr6: a polar uncharged amino acid residue); X7: sarcosine (i.e. Sar7: a non-proteinogenic; a polar uncharged amino acid residue based on p. para. [0034] of the present description as well as a non-proteinogenic amino acid based on p. para. [0024] of the specification filed 04/21/2026); X8:absent; X9: L-serine (i.e. a polar uncharged amino acid residue); X10, X11:absent; and R is NH2, which meets the limitation and within the scope of formula (1) of claim 1, and thus anticipates claims 1-6, 20-23, and 25 (col.23, claim 74). Thus, claims 1-6, 20-23, and 25 are anticipated by De Castiglione (US4350627).
iii. De Castiglione also teaches the peptide of formula I:
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having analgesic activity for the treatment of pain, wherein the “A” is D-amino acid residue including ala, val, ile, leu, pro, ser, thr, met, met-sulphoxide and S-ethyl-homocysteine (in X2); and wherein “B” is L-amino acid residue including Val, Ile, Leu, a glycine residue (in X5); and “C” is an amino acid residue including Gly, Ala, Val, normal valine (Nva), Leu, Ile, a-amino-n-butyric acid (Abu), Phg, Phe, Trp, Tyr, Ser, Thr, Homoserine (Hse), Met, Met-sulfoxide, b-cyclohexylalanine, para-substituted Phe, the substituent being selected from chlorine, bromine, fluorine, amino and nitro…a dipeptide……a tripeptide…J-L-M….(in X6-X9); “W” includes OH, NH2, NH(C1-6alkyl) and N(C1-6alkyl)2 (see col. 1-3; col. 4, line 4-col. 5, line 32; col. 6-26, examples 1-10, claims 1-131), which meets the limitations recited in instant claim 1.
Accordingly, the rejection of claims 1-6, 20-23, and 25 under 35 U.S.C. 102(a)(1) as being anticipated by De Castiglione (US4350627) is maintained.
Double Patenting
10. 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 1-6, 14-15, 17 and 20-25 stand provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 4-13, 16-19 and 21-22 of copending Application No. 17/424649 (the ‘649 Application). The rejection is maintained for the reasons of record and the reasons set forth below.
Response to Arguments
On p. 14-15 of the response, Applicant argues that i) amended claim 1 requires that X2 is selected from glycine, sarcosine, g-aminobutyric acid, L-alanine and L-3-4(-pyridyl)-alanine; and X4 is selected from L/D-phenylalanine or a phenylalanine derivative selected from D/L-4-nitro/chloro/fluoro-phenylalanine with X3 being absent; ii) the claims of the ‘649 Application do not teach the limitations recited in amended claim 1 or SEQ ID NO:19.
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§804 and MPEP §2131, the claims 1, 4-13, 16-19 and 21-22 of the ‘649 Application still anticipate instant claims because:
i. The compound of formula (I) recited in claims 1, 4-13, 16-19 and 21-22 of the ‘649 Application includes a compound/peptide comprising NH2-Tyr1-Sar3-(4-NO2)Phe4-Leu5-NMA6-NMA7 (claim 13) or H-Tyr1-Gly3-(4-NO2)Phe4-Leu5-NMA6-NMA7, which meets the limitations “wherein X1 is tyrosine (Tyr1), X2 is Sarcosine (Sar2) or Glycine (Gly2), X3 is absent, X4 is p-nitrophenylalanine ((4-NO2)Phe4), X5 is Leucine (Leu5), X6 is N(a)-methylarginine (NMA6), and X7 is N(a)-methylarginine (NMA7)” recited in instant claim 1. The compound comprising NH2-Tyr1-Sar3-(4-NO2)Phe4-Leu5-NMA6-NMA7 recited in claim 13 of the ‘649 Application is identical to instant SEQ ID NO:19 (elected) recited in instant claim 24. Therefore, claims 1-6, 14-15, 17 and 20-25 of the instant Application are not patentably distinct from claims1, 4-13, 16-19 and 21-22 of the ‘649 Application because claims 1-6, 14-15, 17 and 20-25 of the instant Application are anticipated by claims 1, 4-13, 16-19 and 21-22 of the ‘649 Application.
Accordingly, the provisional rejection of claims 1-6, 14-15, 17 and 20-25 on the ground of nonstatutory double patenting as being unpatentable over claims 1, 4-13, 16-19 and 21-22 of copending Application No. 17/424649 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 21, 2026.
Claim Rejections - 35 USC § 103
11. 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 1-6, 14-15, 17 and 20-25 are rejected under 35 U.S.C. 103 as being unpatentable over either Ambo et al. (1999) or De Castiglione (US4350627) in view of Carr et al. (US2009/0298755, published Dec 3, 2009, priority Oct 28, 1999, cited previously)
Ambo or De Castiglione is set forth above but fails to teach glycine for X2 as recited in the formula (I) of amended claim 1.
Carr et al. (US2009/0298755) teach chimeric peptides containing an opioid peptide moiety and a nociceptive peptide moiety wherein the opioid moiety includes dynorphin analogs with high kappa receptor selectivity for producing analgesia or treating pain, wherein the dynorphin analogs include a peptide of SEQ ID NO:44 which comprises the sequence of NH2-Tyr1-Gly2-Phe4-Leu5-Arg6-Arg7-Cys8-Arg9-Pro10-Lys11-Leu12-Cys13-NH2 (para. [0051]) and meets the limitations “NH2-Tyr1-Gly2-Phe4-Leu5-Arg6-Arg7” recited in instant claims.
A person of ordinary skill in the art would have recognized that selecting and applying the known glycine for X2, the known sequence comprising “NH2-Tyr1-Gly2-Phe4-Leu5-Arg6-Arg7-” and the known effect of chimeric peptides containing an opioid peptide moiety and a nociceptive peptide moiety for producing analgesia or treating pain disclosed by Carr to the Ambo’s or De Castiglione’s peptide would have yielded the predictable result of generating the claimed compound of formula (I) having “NH2-Tyr1-Gly2-Phe4-Leu5-Arg6-Arg7-” and resulted in an improved product.
Using glycine to replace ala or D-Ala for X2 in the Ambo’s or De Castiglione’s peptide would generate the claimed compound of formula (I) having “NH2-Tyr1-Gly2-Phe4-Leu5-Arg6-Arg7-” and expand application of the Ambo’s or De Castiglione’s peptide for producing analgesia or treating pain, and would increase patient’s satisfaction with treatment of pain using chimeric peptides containing an opioid peptide moiety and a nociceptive peptide moiety because dynorphin analogs include a peptide of SEQ ID NO:44 comprising the sequence of NH2-Tyr1-Gly2-Phe4-Leu5-Arg6-Arg7 which has high kappa receptor selectivity and can be used for producing analgesia or treating pain.
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 glycine for X2, the known sequence comprising “NH2-Tyr1-Gly2-Phe4-Leu5-Arg6-Arg7-” and the known effect of chimeric peptides containing an opioid peptide moiety and a nociceptive peptide moiety for producing analgesia or treating pain disclosed by Carr to the Ambo’s or De Castiglione’s peptide and yield the predictable result of generating the claimed compound of formula (I) having “NH2-Tyr1-Gly2-Phe4-Leu5-Arg6-Arg7-”.
Claim Rejections - 35 USC § 103
12. Claims 1-6, 14-15, 17 and 20-25 are rejected under 35 U.S.C. 103 as being unpatentable over either Ambo et al. (1999) or De Castiglione (US4350627) in view of Carr et al. (US2009/0298755) as applied to claims 1-6, 14-15, 17 and 20-25, and further in view of Ptchelintsev (US8551956, issued Oct 8, 2013, priority Feb 28, 2006).
Ambo, De Castiglione and Carr are set forth above but fail to teach D-phenylalanine or a phenylalanine derivative selected from L/D-4-nitrophenylalanine, L/D-4-chlorophenyalanine, L/D-4-fluorophenylalanine for X4 recited in claim 1.
Ptchelintsev (US8551956) teach the benefits of using non-natural amino acid residues including D-phenylalanine ((D)-Phe)(see col. 18, line 44) or a phenylalanine derivative selected from L/D-4-nitrophenylalanine ((4-NO2)Phe), L/D-4-chlorophenyalanine ((4-Cl)Phe), L/D-4-fluorophenylalanine ((4-F)Phe)(col. 19, lines 1-9) to substitute L-phenylalanine (Phe) for synthesis of peptides to provide enhanced efficacy, resistance to proteolytic degradation for pharmaceutical or cosmetic compositions (see col. 21-22).
A person of ordinary skill in the art would have recognized that selecting and applying the known (D)-Phe or the known Phe derivative including L/D-(4-NO2) Phe, L/D-(4-Cl)Phe, L/D-(4-F)Phe to substitute Phe for synthesis of peptides for pharmaceutical or cosmetic compositions disclosed by Ptchelintsev to the compound/peptide of Ambo/De Castiglione and Carr would have yielded the predictable result of generating the claimed compound of formula (I) having “NH2-Tyr1-Gly2/(D)Ala2-(D)Phe4/(4-NO2)/(4-Cl)/(4-F)Phe4-Leu5-Arg6-Arg7-” and resulted in an improved product.
Using (D)-Phe or the known Phe derivative including L/D-(4-NO2) Phe, L/D-(4-Cl)Phe, L/D-(4-F)Phe to replace Phe in the peptide/compound of Ambo/De Castiglione and Car would generate the claimed compound of formula (I) having “NH2-Tyr1-Gly2/(D)Ala2-(D)Phe4/(4-NO2)/(4-Cl)/(4-F)Phe4-Leu5-Arg6-Arg7-” to provide enhanced efficacy, resistance to proteolytic degradation of the claimed compound of formula (I), and expand application of the compound/peptide of Ambo/De Castiglione and Carr for producing analgesia or treating pain, and would increase patient’s satisfaction with treatment of pain using chimeric peptides containing an opioid peptide moiety and a nociceptive peptide moiety because (D)-Phe and the Phe derivative including L/D-(4-NO2) Phe, L/D-(4-Cl)Phe, L/D-(4-F)Phe have been used to replace Phe for synthesis of peptides to provide enhanced efficacy, resistance to proteolytic degradation for pharmaceutical or cosmetic compositions disclosed by Ptchelintsev and Ambo/De Castiglione and Car have taught the claimed compound of formula (I) having “NH2-Tyr1-Gly2/(D)Ala2-Phe4-Leu5-Arg6-Arg7-“ for producing analgesia or treating pain.
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 (D)-Phe or the known Phe derivative including L/D-(4-NO2) Phe, L/D-(4-Cl)Phe, L/D-(4-F)Phe to substitute Phe for synthesis of peptides to provide enhanced efficacy, resistance to proteolytic degradation for pharmaceutical or cosmetic compositions disclosed by Ptchelintsev to the compound/peptide of Ambo/De Castiglione and Carr and yield the predictable result of generating the claimed compound of formula (I) having “NH2-Tyr1-Gly2/(D)Ala2-(D)Phe4/(4-NO2)/(4-Cl)/(4-F)Phe4-Leu5-Arg6-Arg7-”.
Conclusion
13. NO CLAIM IS ALLOWED.
14. The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Carr et al. (US6759520) disclosed Dynorphin (DYN) related peptides including Dynorphin A, DYN(1-8) and DYN(1-13) (table 3).
Morgan et al. (Peptides, 2017; 89:9-16) teaches Dynorphin fragments (Dynorphin 1-6, 1-7 and 1-9) mediate analgesia (abstract; p. 11-15).
Hall et al. (Future Med. Chem.2016; 8 (2):165-177) teach an antinociceptive peptide, SK-9709, comprises the sequence of H-Y-a-F-L-RΨ(CH2NH)-Arg-NH2, which meets the limitations recited in instant claims (p. 168, 2nd col., 1st paragraph; p. 169, table 3).
15. 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.
16. 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.
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Chang-Yu Wang
June 22, 2026
/CHANG-YU WANG/Primary Examiner, Art Unit 1675
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