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
Status of Application/Election/Restrictions
Applicant’s election without traverse of Group I (claims 1-6, 14-15, 17 and 20-25) and SEQ ID NO:19 in the reply filed on October 3, 2025 is acknowledged.
Claims 7-13, 16, 18-19, 27-28 and 30 are canceled. 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 Claims 26 and 29 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to nonelected inventions, there being no allowable generic or linking claim.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.
Claims 1-6, 14-15, 17 and 20-25 are under examination with respect to SEQ ID NO: 19 in this office action.
Specification
The disclosure is objected to because of the following informalities: The use of the term “ALPHAScreen” ([0096])-[0097]), “Milli-Q” ([00107]), which is a trade name or a mark used in commerce, has been noted in this application. The term 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.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks. Appropriate correction is required.
Claim Rejections - 35 USC § 112
5. 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 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
To provide adequate written description and evidence of possession of a claimed genus, the specification must provide sufficient distinguishing identifying characteristics of the genus. The factors to be considered include disclosure of complete or partial structure, physical and/or chemical properties, functional characteristics, structure/function correlation, methods of making the claimed product, or any combination thereof.
Claims 1-6, 14-15, 17 and 20-25 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 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.
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 has close IC50 as U50488H but not SEQ ID NOs: 4, 20 or 24 (Table 7); iii) only SEQ ID NOs:4, 18 and 19 do not cause KOR desensitization (00112], Example 8, figure 4); iv) SEQ ID NO:24 showed some influence over pEerk induction and SEQ ID NOs: 4, 18 and 19 failed to show any pERK activity (Example 9, Figure 5); v) SEQ ID NOs: 4 and 19 showed better efficacy than U50488H, and SEQ ID NOs: 19 and 24 showed statistically significantly greater over morphine in FCA model (Example 10, figure 6). However, the claims are not limited to the peptides set forth above but also encompass structurally and functionally undefined peptides.
In making a determination of whether the application complies with the written description requirement of 35 U.S.C. 112, first paragraph, it is necessary to understand what Applicant is in possession of and what Applicant is claiming.
M.P.E.P. § 2163 instructs:
An invention described solely in terms of a method of making and/or its function may lack written descriptive support where there is no described or art-recognized correlation between the disclosed function and the structure(s) responsible for the function. . . .
An applicant may show possession of an invention by disclosure of drawings or structural chemical formulas that are sufficiently detailed to show that applicant was in possession of the claimed invention as a whole. . . .
An applicant may also show that an invention is complete by disclosure of sufficiently detailed, relevant identifying characteristics which provide evidence that applicant was in possession of the claimed invention, i.e., complete or partial structure, other physical and/or chemical properties, functional characteristics when coupled with a known or disclosed correlation between function and structure, or some combination of such characteristics.”
This standard has not been met in this case. From the specification, it is clear that Applicant is in possession of peptides recited in Table 5 having similar activity of EC50 to that of CR845 (SEQ ID NO:35) or in possession of peptide of SEQ ID NO:4 or SEQ ID NO:19 that does not cause KOR desensitization. However, Applicant is not in possession of other structurally and functionally undefined compound of formula I. The specification provides no identification of any particular portion of the structure that must be conserved. The instant specification fails to provide sufficient descriptive information, such as definitive structural or functional features of the claimed genus of compound of formula I because a single amino acid change on a molecule or protein can abolish the activity or binding ability of the molecule or protein. For example, a substitution of lysine residue by glutamic acid at position 118 of acidic fibroblast growth factor results in a substantial loss of its biological activity including the binding ability to heparin and its receptor (Burgess et al. J of Cell Bio. 1990, 111:2129-2138). Although many amino acid substitutions are possible in any given protein, the position of where such amino acid substitutions can be made is critical for maintaining the function of a protein; i.e. only certain positions can tolerate conservative substitutions without changing the relationship of three dimensional structure and function of the protein (col 2, p. 1306, Bowie et al. Science, 1990, 247:1306-1310). Even if an active or binding site were identified in the specification, they may not be sufficient, as the ordinary artisan would not immediately recognize that an active or binding site must assume the proper three-dimensional configuration to be active because conformation is dependent upon surrounding residues; i.e. substitution of non-essential residues can often destroy activity. In addition to a core determinant sequence, the protein-protein interaction also relies on the flanking or noncontiguous residues (see p. 445 the second column, first paragraph, Pawson et al. 2003, Science 300:445-452). The optimal binding motif for a domain is not necessarily suitable for physiological or in vivo interaction. The predictive data always need to be validated by actual analyses in cells (see p. 445, the third column, second paragraph, Pawson et al. 2003, Science 300:445-452). Alaoui-lsmaili teaches that designing a mutein having predictable activities is difficult because of the complexity of the interactions between ligands and receptors (Alaoui-lsmaili et al., Cytokine Growth Factor Rev. 2009; 20:501-507). For example, given the complexity of BMP-BMP receptor interactions, it is difficult to design BMPs with improved affinity and/or specificity for one specific receptor. More importantly, predicting the in vivo biological activity of such altered BMPs remains a challenging undertaking (see p. 502, right col., 2th paragraph). Further, when multiple mutations are introduced, there is even less predictability because Guo et al. teaches that the effects of mutations on protein function are largely additive (see p. 9207, left col., 2th paragraph, Guo et al., PNAS 2004; 101:9205-9210). Applicant fails to teach what other structures/amino acid sequences can nor cannot be included/changed in compounds of formula in order to preserve the activity of SEQ ID NO:4 or 19 or peptides in table 5. There is no description of the sites at which variability may be tolerated and there is no information regarding the relation of structure of other compounds of formula to the function of peptides recited in Table 5 or SEQ ID NO:4 or 19. Furthermore, the prior art does not provide compensatory structural or correlative teachings sufficient to enable one of skill to identify what other compounds of formula I might be.
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. Accordingly, in the absence of sufficient recitation of distinguishing identifying characteristics, the specification does not provide adequate written description of the genus of compounds 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 compounds 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.
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.
6. In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
Claim Rejections - 35 USC § 102
7. 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 are 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).
Claims 1-6, 14-15, 17, 20-23 and 25 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/D-tyrosine, L/D-phenylalanine, L/D-3-(4-pyridyl)-alanine or derivatives thereof;
X2 is glycine, sarcosine, N-alkylglycine,4-aminobutyric acid, L/D-leucine, L/D-isoleucine, L/D-valine, L/D-alanine, or L/D-3-(4-pyridyl)-alanine;
X3 is absent;
X4 is L/D-phenylalanine, L/D-leucine, or derivatives thereof
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 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 or X7 is a non-proteinogenic amino acid; are selected from the residues, structures and features recited in independent claim 1.
Ambo et al. teach synthesis of hybrid analogs of dermorphin-dynorphin having high binding affinity to kappa opioid receptor, and enzymatic stability, which meet the limitations recited in instant claims 1, 4-6, 20-23 and 25 (see p. 702, Table 1: peptides (1) to (10)). In particular, the peptide (9): YAFLRmeR-NHEt disclosed by Ambo meets the limitation within the scope of formula (I) of instant claim 1 wherein R1: hydrogen; X1: L-tyrosine; X2: D-alanine (a non-proteinogenic amino acid); X3 =absent; X4: L-phenylalanine; X5: L-leucine; X6: L-arginine (i.e. a positively charged amino acid residue per paragraph [0032] of the present description); X7: N-methyl-L-arginine (i.e. a positively charged amino acid residue per paragraph [0032] 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.
The peptide (2): YAFLRRI-NH2 disclosed by Ambo also mees the limitation and within the scope of formula (I) of claim 1 wherein R=hydrogen; X1=L-tyrosine; X2 =D-alanine (a non-proteinogenic amino acid); X3=absent; X4=L-phenylalanine; X5 =L-leucine; X6= X7 =L-arginine (i.e. a positively charged amino acid residue); X8 =L-isoleucine (a hydrophobic amino acid residue per paragraph [0031] of the present description); X9=X10=X11=absent; and R2 is NH, and thus anticipates claims 1-6, 14-15, 17, 20-23 and 25. Therefore, claims 1-6, 14-15, 17, 20-23 and 25 are anticipated by Ambo.
8. Claims 1-6, 20-23, and 25 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by De Castiglione (US Patent No. 4350627, issued Sep 21, 1982, priority Sep 20, 1979; as in IDS).
De Castiglione (US4350627) teach a peptide of formula I: X-Tyr-A-Phe-B-C-W having analgesic activity for the treatment of pain, wherein “X” is hydrogen, or alky-type protection group; “A” is a D-amino acid; “B” is a neutral amino acid residue, glycine or N-methyl amino acid; “C” is an amino acid or di- or tripeptide residue and W is OH, OR, NH2, NHR, N(R)2, NH-NH2, wherein “R” is an alkyl, cycloalkyl or aralkyl C1-7 or NHNHR’ wherein “R’” is hydrogen, C1-10 or C2-8 or a residue of a-amino acid, a-imino or b-amino acid having L or D configuration or a residue of a di- or tripeptide and a pharmaceutical composition comprising the claimed peptide, which meet the limitations recited in instant claims 1-6, 20-23, and 25 (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). De Castiglione administering the peptides together with pharmaceutically acceptable carriers and diluents as in claim 25 (see col. 6, lines 39-45; col. 6-16, Examples1- 10).
In particular, the peptide derivative (29) disclosed by De Castiglione comprises R: hydrogen; X1: L-tyrosine; X2: D-alanine (a non-proteinogenic amino acid per paragraph [0024] of the present description); X3: absent; X4: L-phenylalanine; X5: glycine; X6: L-tyrosine (i.e. a polar uncharged amino acid residue per paragraph [0034] of the present description); X7 = L-serine (i.e. a polar uncharged amino acid residue per paragraph [0034] of the present description); X8, X9, X10, X11: absent; and R2: NH, which meets the limitation and within the scope of formula (I) of claim 1 (see col. 11, Example 5, lines46-47, and claim 16) and thus the derivative (29) anticipates claims 1, 4-6, 20-23, and 25.
The peptide derivative in claim 24 disclosed by De Castiglione comprises R1: hydrogen; X1: L-tyrosine; X2: D-alanine (a non-proteinogenic amino acid per paragraph [0024] of the present description); X3: absent; X4: L-phenylalanine; X5: glycine; X6: L-tyrosine (i.e. a polar uncharged amino acid residue per paragraph [0034] of the present description); X7 = glycine (i.e. a polar uncharged amino acid residue per paragraph [0034] of the present description); X8: absent; X9:L-serine (i.e. a polar unchanged amino acid residue); X10= X11: absent; and R2: NH, which meets the limitation and within the scope of formula (I) of claim 1, and thus anticipates claims 1, 4-8, 12, 20, 22, 23, and 25 (col. 21, claim 24).
The peptide derivative in claim 74 disclosed by De Castiglione comprises R: hydrogen; X1: L-tyrosine; X2: D-alanine (a non-proteinogenic amino acid); X3: absent; X4: L-phenylalanine; X5: glycine; X6: L-tyrosine (i.e. a polar uncharged amino acid residue); X7: sarcosine (i.e. a polar uncharged amino acid residue per paragraph [0034] of the present description as well as a non-proteinogenic amino acid per paragraph [0024] of the present description); 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).
Double Patenting
9. 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 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-19 and 21 of copending Application No. 17/424649 (the ‘649 Application). Although the claims at issue are not identical, they are not patentably distinct from each other because the compound of formula I or salt or stereoisomer or solvate or prodrug thereof and sequences recited in claims 1-19 and 21 of the ‘649 Application Application anticipate instant claims.
Claims 1-19 and 21 of the ‘649 Application claim a compound of formula I or salt or stereoisomer or solvate or prodrug thereof or and a method of use the compound, wherein the compound of formula I comprises residues and features recited in instant claims and thus anticipate instant claims; in particular, wherein X1 is tyrosine (Tyr), X2 is absent, X3 is Sarcosine (Sar), X4 is p-nitrophenylalanine ((4-NO2)Phe), X5 is Leucine (Leu), X6 is N(a)-methylarginine (NMA), and X7 is N(a)-methylarginine (NMA), which is identical to instant SEQ ID NO:19 (elected) recited in claim 24. Therefore, claims 1-6, 14-15, 17 and 20-25 of the instant Application are not patentably distinct from claims 1-19 and 21 of the ‘649 Application because claims 1-6, 14-15, 17 and 20-25 of the instant Application are anticipated by claims 1-19 and 21 of the ‘649 Application.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
10. NO CLAIM IS ALLOWED.
11. The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Carr et al. (US2009/0298755, published Dec 3, 2009, priority Oct 28, 1999) teach dynorphin analgos with high kappa receptor selectivity including a peptide of SEQ ID NO:44 which comprises the sequence of Tyr-Gly-Phe-Leu-Arg-Arg (para. [0051]).
Carr et al. (US6759520, issued Jul 6, 2004, filed Oct 28, 1999) disclosed Dynorphin (DYN) related peptoides 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).
12. 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 on Monday-Thursday, 7:00am-5:00pm EST.
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Chang-Yu Wang
October 18, 2025
/CHANG-YU WANG/Primary Examiner, Art Unit 1675