DETAILED CORRESPONDENCE
Status of the Application
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claims 69-73, 75-82, and 86-92 are pending in the application.
Applicant’s amendment to the claims, filed January 9, 2026, is acknowledged. This listing of the claims replaces all prior versions and listings of the claims.
Applicant’s remarks filed January 9, 2026 in response to the non-final rejection filed July 9, 2025 are acknowledged and have been fully considered.
Rejections previously applied to claims 74 and 83-85 are withdrawn in view of applicant’s amendment to cancel these claims.
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Restriction/Election
In response to a requirement for restriction/election filed December 20, 2024, applicant elected without traverse the invention of Group II, corresponding to pending claims 73 and 88-92, and the species of SEQ ID NO: 18 in the reply filed June 25, 2025. is acknowledged.
Claims 69-72, 75-82, 86, and 87 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.
Claims 73 and 88-92 are being examined on the merits.
Specification/Informalities
The substitute specification filed on June 20, 2023 is objected to because the size of the XML file in the sequence incorporation statement at paragraph [0002] must be listed in bytes (not kilobytes). See MPEP 2422.03.I. Appropriate correction is required.
Claim Rejections - 35 USC § 112(b)
The rejection of claim 73 under 35 U.S.C. 112(b) as being indefinite in the recitation of “functional variants thereof” is withdrawn in view of applicant’s amendment to claim 73.
Claim Rejections - 35 USC § 112(a)
The rejections of claim 73 under 35 U.S.C. 112(a) as failing to comply with the written description and enablement requirements are withdrawn in view of applicant’s amendment to claim 73 to limit the claimed polypeptide to consisting of an amino acid sequence having at least 80% identity to SEQ ID NO: 54, wherein the polypeptide exhibits neopinone isomerase activity.
Claims 73, 88-90, and 92 are newly rejected under 35 U.S.C. 112(a) 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 at the time the application was filed, had possession of the claimed invention. This is a new matter rejection and is necessitated by applicant’s claim amendment.
MPEP § 2163.II.A.3.(b) states, “when filing an amendment an applicant should show support in the original disclosure for new or amended claims”. See also MPEP 714.02. MPEP § 2163.II.A.3.(b) further states, “[i]f the originally filed disclosure does not provide support for each claim limitation, or if an element which applicant describes as essential or critical is not claimed, a new or amended claim must be rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112, para. 1, as lacking adequate written description”. According to MPEP § 2163.I.B, “While there is no in haec verba requirement, newly added claim limitations must be supported in the specification through express, implicit, or inherent disclosure” and “The fundamental factual inquiry is whether the specification conveys with reasonable clarity to those skilled in the art that, as of the filing date sought, applicant was in possession of the invention as now claimed. See, e.g., Vas-Cath, Inc., 935 F.2d at 1563-64, 19 USPQ2d at 1117.”
Claim 73 (claims 88-90 and 92 dependent therefrom) has been amended to recite “an amino acid sequence having at least 80% identity to SEQ ID NO: 54” and newly added claims 88-90 recite an amino acid sequence having at least 85%, 90%, and 95% identity, respectively, to SEQ ID NO: 54. Applicant cites to paragraph [0314] of the published application (corresponding to paragraph [0212] of the substitute specification filed June 20, 2023) for descriptive support for the claim amendments. The cited support fails to disclose 80% and 85% identity, and while the cited support discloses 90% and 95% identity, this disclosure is in reference to nucleotide sequences and not the amino acid sequence of SEQ ID NO: 54. Applicant is invited to show support for the limitations at issue. In the absence of descriptive support, the noted limitations in claims 73, 88-90, and 92 introduce new matter into the claims.
Claim Rejections - 35 USC § 102
Claims 73 and 88-92 are rejected under 35 U.S.C. 102(a)(1) or 102(a)(2) as being anticipated by Facchini et al. (WO 2018/005553 A1; cited on the IDS filed on December 22, 2022; hereafter “Facchini”). This rejection has been modified from its previous version to address applicant’s claim amendment. For reasons set forth in the prior Office action (pp. 3-4 of the Office action filed July 9, 2025 under the heading “Priority”), the effective filing date of claims 73 and 88-92 is June 8, 2018.
Claims 73 and 88-91 are drawn to a polypeptide consisting of an amino acid sequence having at least 80%, 85%, 90%, 95%, or 100% identity to SEQ ID NO: 54, wherein the polypeptide exhibits neopinone isomerase activity.
Claim 92 is drawn to the polypeptide of claim 73, wherein the polypeptide is an isolated polypeptide.
Regarding claims 73 and 88-91, Facchini teaches a thebaine synthesis polypeptide having the sequence of SEQ ID NO: 5 (paragraph [0226]). SEQ ID NO: 5 of Facchini consists of SEQ ID NO: 54 of this application.
Facchini does not teach or suggest the thebaine synthesis polypeptide exhibits neopinone isomerase activity. However, according to MPEP 2112.01, when the structure recited in the reference is substantially identical to that of the claims, claimed properties or functions are presumed by be inherent. In accordance with MPEP 2112.01, since the thebaine synthesis polypeptide of Facchini consists of SEQ ID NO: 54 of this application, it is presumed that the thebaine synthesis polypeptide of Facchini exhibits neopinone isomerase activity.
Regarding claim 92, Facchini teaches the thebaine synthesis polypeptide is isolated (paragraph [0195]).
Therefore, Facchini anticipates claims 73 and 88-92 as written.
Claims 73 and 88-92 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Chen et al. (Nature Chemical Biology 14:738-743, May 2018; cited on Form PTO-892 filed July 9, 2025; hereafter “Chen”) as evidenced by Supplementary Information (May 2018, 46 pages; cited on Form PTO-892 filed July 9, 2025; hereafter “Supplementary Information”). This rejection has been modified from its previous version to address applicant’s claim amendment. For reasons set forth in the prior Office action (pp. 3-4 of the Office action filed July 9, 2025 under the heading “Priority”), the effective filing date of claims 73 and 88-92 is June 8, 2018.
Regarding claims 73 and 88-92, Chen teaches a purified polypeptide referred to as “PR10-3” (p. 740, Fig. 3). Evidentiary reference Supplementary Information is cited in accordance with MPEP 21313.01.III to show that the amino acid sequence of PR10-3 (p. 8, Supplementary Figure 6) consists of SEQ ID NO: 54 of this application.
Chen does not teach or suggest PR10-3 exhibits neopinone isomerase activity. However, according to MPEP 2112.01, when the structure recited in the reference is substantially identical to that of the claims, claimed properties or functions are presumed by be inherent. In accordance with MPEP 2112.01, since the sequence of PR10-3 consists of SEQ ID NO: 54 of this application, it is presumed that PR10-3 of Chen exhibits neopinone isomerase activity.
Therefore, Chen anticipates claims 73 and 88-92 as written.
Claims 73 and 88-92 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Enquist-Newman et al. (WO 2019/051046 A1 with priority to September 8, 2017; cited on Form PTO-892 filed July 9, 2025; hereafter “Enquist-Newman”). This rejection has been modified from its previous version to address applicant’s claim amendment. For reasons set forth in the prior Office action (pp. 3-4 of the Office action filed July 9, 2025 under the heading “Priority”), the effective filing date of claims 73 and 88-92 is June 8, 2018.
Regarding claims 73 and 88-91, Enquist-Newman teaches a thebaine synthase polypeptide comprising SEQ ID NO: 51 (paragraph [00094]). SEQ ID NO: 51 of Enquist-Newman consists of SEQ ID NO: 54 of this application.
Enquist-Newman does not teach or suggest the thebaine synthase polypeptide exhibits neopinone isomerase activity. However, according to MPEP 2112.01, when the structure recited in the reference is substantially identical to that of the claims, claimed properties or functions are presumed by be inherent. In accordance with MPEP 2112.01, since the thebaine synthase polypeptide of Enquist-Newman consists of SEQ ID NO: 54 of this application, it is presumed that the thebaine synthase polypeptide of Enquist-Newman exhibits neopinone isomerase activity.
Regarding claim 92, Enquist-Newman teaches the enzyme is isolated (paragraph [000168]).
Therefore, Enquist-Newman anticipates claims 73 and 88-92 as written.
RESPONSE TO REMARKS: Applicant argues neither Facchini, Chen, nor Enquist-Newman teaches or suggests the polypeptide of claim 73.
Applicant’s arguments are not found persuasive. For the reasons set forth above, each of Facchini, Chen, and Enquist-Newman anticipates claims 73 and 88-92 as written.
Claim Rejections - 35 USC § 101
Claims 73 and 88-92 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception (i.e., a law of nature, a natural phenomenon, or an abstract idea) without significantly more. Applicant’s attention is directed to the "Guidance for Determining Subject Matter Eligibility Of Claims Reciting Or Involving Laws of Nature, Natural Phenomena, & Natural Products”, released on December 16, 2014. This rejection has been modified from its previous version to address applicant’s claim amendment.
Claim Interpretation: Claims 73 and 88-91 are drawn to a polypeptide consisting of an amino acid sequence having at least 80%, 85%, 90%, 95%, or 100% identity to SEQ ID NO: 54, wherein the polypeptide exhibits neopinone isomerase activity.
Claim 92 is drawn to the polypeptide of claim 73, wherein the polypeptide is an isolated polypeptide.
For reasons set forth above in the rejections under 35 U.S.C. 102, each of Facchini, Chen, and Enquist-Newman teaches a naturally-occurring polypeptide consisting of the amino acid sequence of SEQ ID NO: 54.
Moreover, claims 73, 88, and 92 encompass a naturally-occurring P. somniferum neopinone isomerase of instant SEQ ID NO: 2 for reasons that follow. SEQ ID NO: 54 is a fragment of SEQ ID NO: 2 (see substitute specification filed June 20, 2023 at paragraph [0325]) and SEQ ID NO: 2 is identical to the amino acid sequence of Papaver somniferum neopinone isomerase as disclosed by GenBank Accession Number QBG82386 (April 2019, 1 page; cited on Form PTO-892 filed July 9, 2025). Claims 73 and 92 allow up to 20% amino acid modifications (e.g., amino acid additions to the N-terminus of SEQ ID NO: 54) relative to the 158 amino acid sequence of SEQ ID NO: 54, while claim 88 allows up to 15% amino acid modifications relative to SEQ ID NO: 54. Given that 20% of 158 is 31.6, claims 73 and 92 encompass polypeptides having approximately 32 amino acid additions to the N-terminus of SEQ ID NO: 54, and given that 15% of 158 is 23.7, claim 88 encompasses polypeptides having approximately 24 amino acid additions to the N-terminus of SEQ ID NO: 54. SEQ ID NO: 2 has 18 amino acid additions to the N-terminus of SEQ ID NO: 54, and claims 73, 88, and 92 encompass the naturally-occurring P. somniferum neopinone isomerase of instant SEQ ID NO: 2.
Given a broadest reasonable interpretation, claims 73 and 88-92 encompass naturally-occurring polypeptides.
Patent Eligibility Analysis Step 1: The claims are drawn to a polypeptide, which is a composition of matter and is one of the statutory categories of invention.
Patent Eligibility Analysis Step 2A Prong 1: There is no evidence of record that polypeptides encompassed by claims 73 and 88-92 have markedly different characteristics from their naturally-occurring counterparts.
Patent Eligibility Analysis Step 2A Prong 2: There are no additional elements recited in the claims beyond the judicial exception.
Patent Eligibility Analysis Step 2B: The claims only recite a law of nature and do not include any additional elements that could add significantly more to the judicial exception.
As such, the claims do not qualify as eligible subject matter. For these reasons the claims are rejected under section 101 as being directed to non-statutory subject matter.
RESPONSE TO REMARKS: Applicant argues that by amendment to claim 73, the claims exclude the full-length naturally-occurring P. somniferum neopinone isomerase of SEQ ID NO: 2 and contends that the claimed fragments of SEQ ID NO: 2 including SEQ ID NO: 54 do not exist in nature. Applicant argues that the polypeptides comprising SEQ ID NO: 54 enable efficient biosynthetic production of morphinan intermediates-specifically, the conversion of neopinone and neomorphinone into codeinone and morphinone and the application includes in vitro and in vivo data demonstrating increased yields of codeinone, morphinone, codeine, and morphine when the polypeptides of SEQ ID NO: 54 are introduced. Applicant argues these technological improvements are meaningful, measurable, and tied to specific structural features of the truncated polypeptide and therefore, according to applicant, the claims are directed to a practical application of a human-made biomolecule, not an abstract idea.
Applicant’s arguments are not found persuasive. As stated above and contrary to applicant’s position, claims 73 and 88-92 encompass naturally occurring polypeptides disclosed by each of Facchini, Chen, and Enquist-Newman. Moreover, as described above, claims 73, 88, and 92 encompass the naturally-occurring P. somniferum neopinone isomerase of instant SEQ ID NO: 2. Furthermore, even if the claims were limited to man-made fragments of a naturally-occurring P. somniferum neopinone isomerase, there is no evidence of record that such fragments have markedly different characteristics from the full-length polypeptide from which the fragments are derived, and in accordance with MPEP 2106.04(c).II.C.2, such fragments would not be considered markedly different.
For these reasons, the claims do not qualify as patent eligible subject matter.
Claim Rejections - Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The 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/process/file/efs/guidance/eTD-info-I.jsp.
Claims 73 and 88-92 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 42 and 45 of co-pending application no. 19/186,191 (reference application). This provisional rejection has been modified from its previous version to address applicant’s claim amendment.
Claim 42 of the reference application recites a method of making a BIA outside of a cell comprising,
contacting a substrate that is capable of being converted by one or more enzymes, wherein the one or more enzymes comprise a tyrosine hydroxylase (TYR); DOPA decarboxylase (DODC); norcoclaurine synthase (NCS); 6-O-Methyltransferase (6OMT); coclaurine N-methyltransferase (CNMT), cytochrome P450 N- methylcoclaurine hydroxylase (NMCH), and 4-O-methyltransferase (4OMT); cytochrome P450 reductase (CPR), salutaridine synthase (SAS); salutaridine reductase (SalR ); salutaridinol-7-O-acetyltransferase (SalAT); purine permease (PUP); or any combination thereof;
contacting the product of a) with one or more of a thebaine synthesis polypeptide; a codeine O-demethylase (CODM); a thebaine 6-O-demethylase (T6ODM); a codeinone reductase (COR); or any combination thereof, and
claim 45 of the reference application recites the method of claim 42, wherein the product of a) is contacted with a thebaine synthesis polypeptide.
According to MPEP 804.II.B.1, the portion of the specification of the reference that describes subject matter that falls within the scope of a reference claim may be relied upon to properly construe the scope of that claim and in view of the specification at paragraph [000226] of the reference application, SEQ ID NO: 5 of the reference application is within the scope of the recited thebaine synthesis polypeptide of claims 42 and 45. SEQ ID NO: 5 of the reference application consists of SEQ ID NO: 54 of this application.
Claims 42 and 45 of the reference application do not recite the thebaine synthesis polypeptide exhibits neopinone isomerase activity. However, according to MPEP 2112.01, when the structure recited in the reference is substantially identical to that of the claims, claimed properties or functions are presumed by be inherent. In accordance with MPEP 2112.01, since the thebaine synthesis polypeptide of claims 42 and 45 of the reference application consists of SEQ ID NO: 54 of this application, it is presumed that the thebaine synthesis polypeptide of claims 42 and 45 of the reference application exhibits neopinone isomerase activity.
Therefore, claims 73 and 88-92 of this application are unpatentable over claims 42 and 45 of the reference application. This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
RESPONSE TO REMARKS: Applicant will address the obviousness double patenting rejection, to the extent necessary, upon an indication that the claims are otherwise in condition for allowance. Applicant’s remarks regarding the provisional obviousness-type double patenting rejection are acknowledged.
Conclusion
Status of the claims:
Claims 69-73, 75-82, and 86-92 are pending.
Claims 69-72, 75-82, 86, and 87 are withdrawn.
Claims 73 and 88-92 are rejected.
No claim is in condition for allowance.
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to DAVID J STEADMAN whose telephone number is (571)272-0942. The examiner can normally be reached Monday to Friday, 7:30 AM to 4:00 PM.
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/David Steadman/Primary Examiner, Art Unit 1656