DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Priority
This application is a 371 of PCT/EP2022/062130, filed 5/05/2022. This application claims benefit to foreign application EP 21172832.4, filed 5/07/2021. Claims 1-6, 9, 13, 16, 25-26, 29-31, 39-40, 49, 73, 77, 94 and 96 are pending.
Election/Restrictions
Applicant’s election without traverse of Group I, claims 1-6, 9-10, 13, 16, 18, 25-26, 29 and 96 in the reply filed on 2-2-2026 is acknowledged. Claims 30-31, 39-40, 49, 73, 77 and 94 have been amended to depend from claim I; hence, claims 1-6, 9, 13, 16, 25-26, 29-31, 39-40, 49, 73, 77, 94 and 96 are pending and have been examined on the merits.
Information Disclosure Statement
The information disclosure statement submitted on 10/23/2023 has been considered by the examiner.
Drawings
The drawings are objected to for the following reasons:
37 CFR 1.84 (u)(1) states "View numbers must be preceded by the abbreviation "FIG."" In the instant application, the view numbers for Figures 1-10 are preceded by the word "Figure" instead of the abbreviation "FIG.".
37 CFR 1.84(i) states "Words must appear in a horizontal, left-to-right fashion when the page is either upright or turned so that the top becomes the right side, except for graphs utilizing standard scientific convention to denote the axis of abscissas (of X) and the axis of ordinates (of Y)." In the instant application, the figure label in Figs. 9 and 10 should be in the same orientation as the figures themselves, i.e., Figs. 9 and 10 are oriented to be viewed wherein the top becomes the right side; hence, the figure labels should appear in a horizontal, left-to-right fashion when the page is turned so that the top becomes the right side.
Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Claim Objections
Claims 1, 3, 13, 16, 26, 29, 39-40, 77, 94 and 96 are objected to because of the following informalities:
Claim 1, line 2, recites “a oripavine acceptor” which should be “an oripavine acceptor” because it is the appropriate article.
Claim 3 recites “is Uridine” which should be “is uridine” because chemical compound names are not capitalized.
Claim 13 recites “pH 7,4” and “0,5 mM” in line 4, which should be “pH 7.4” and “0.5 mM”, respectively, because decimal points are represented by periods, not commas, in American English.
Claim 16 recites “pH 7,4” and “0,5 mM” in line 4, which should be “pH 7.4” and “0.5 mM”, respectively, because decimal points are represented by periods, not commas, in American English.
Claim 26 recites “comprised in any one of SEQ ID NO: 153 155, 157, 256, or 258” which should be “comprised in any one of SEQ ID NOs: 153, 155, 157, 256, or 258” because there is a plurality of SEQ ID NOs and because there should be a comma between “153” and “155”.
Claim 29 recites “UGT’s” in line 2, which should be “UGT[[‘]]s”, i.e., without the apostrophe, because the term is drawn to multiple UGTs, not to a possessed characteristic of an UGT.
Claim 39 recites “one or more UGT’s” in line 4, which should be “one or more UGT[[’]]s”, i.e., without the apostrophe, because the term is drawn to multiple UGTs, not to a possessed characteristic of an UGT.
Claim 39 recites “a oripavine acceptor” in line 5, which should be “an oripavine acceptor” because it is the appropriate article.
Claim 40 recites many chemical compounds with inappropriate capitalization which is inconsistent even within the claim itself wherein instances of the compound occur capitalized as well as correctly uncapitalized. Chemical compounds should not be capitalized; hence, removal of the inappropriate capitalization is required. For example, “Chorismate” in lines 9-10 should be “chorismate”; “Tyrosine” in lines 12 and 16 should be “tyrosine”; “Dopamine” in line 20 should be “dopamine”; “Coclaurine” in lines 23, 24 and 27 should be “coclaurine”; “Hydroxy” in lines 23, 28 and 31 should be “hydroxy”; “Methylcoclaurine” in lines 25, 28, 29 and 31 should be “methylcoclaurine”; “Reticuline” in lines 31 and 33 should be “reticuline”; “Salutaridine” in lines 34 and 35 should be “salutaridine”; and “Salutaridinol” in lines 35 and 36 should be “salutaridinol”.
Claim 77 recites “Kluyveromyces lactis, Saccharomyces carlsbergensis, Saccharomyces cerevisiae, Saccharomyces diastaticus, Saccharomyces douglasii, Saccharomyces kluyveri, Saccharomyces norbensis, Saccharomyces oviformis, and Yarrowia lipolytica” which should be “Kluyveromyces lactis, Saccharomyces carlsbergensis, Saccharomyces cerevisiae, Saccharomyces diastaticus, Saccharomyces douglasii, Saccharomyces kluyveri, Saccharomyces norbensis, Saccharomyces oviformis, and Yarrowia lipolytica” because taxonomic names are italicized.
Claim 94 recites “anyone of SEQ ID NO: 165 or 167” in line 3 and in line 4 which should be “any one of SEQ ID NOs: 165 or 167” because “anyone” has a completely different meaning than “any one” and because there is a plurality of SEQ ID NOs being disclosed.
Claim 96 recites “one or more UGT's” in lines 5-6, which should be “one or more UGT[[’]]s”, i.e., without the apostrophe, because the term is drawn to multiple UGTs, not to a possessed characteristic of an UGT.
Claim 96 recites “a oripavine acceptor” in line 6, which should be “an oripavine acceptor” because it is the appropriate article.
Appropriate correction is required.
Claim Rejections - 35 USC § 112
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 1-6, 9, 13, 16, 25-26, 29-31, 39-40, 49, 73, 77, 94 and 96 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 applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 1, lines 8-9, recites the limitation "wherein the UGT comprises an amino acid sequence which has at 70% identity to the UGT comprised in SEQ ID NO: 92" wherein it is indefinite whether the phrase “which has at 70% identity” means that the UGT must have exactly 70% identity to SEQ ID NO: 92, as written, or that the UGT has at least 70% identity to SEQ ID NO: 92, which is not what is written but would appear to be a reasonable interpretation in the context of the instant disclosure because no UGT with exactly 70% identity to SEQ ID NO: 92 is disclosed in the instant disclosure. Claims 2-6, 9, 13, 16, 25-26, 29-31, 39-40, 49, 73, 77, 94 and 96 depend from claim 1 but do not resolve the indefiniteness; hence, claims 1-6, 9, 13, 16, 25-26, 29-31, 39-40, 49, 73, 77, 94 and 96 are rejected under 35 U.S.C. 112(b) as being indefinite.
Undefined abbreviations of materials recited in the claims renders the claims indefinite. The abbreviations “NDP-glycoside” recited in claim 2 and “PEP”, “E4P”, “DHAP”, “4-HPP”, “TH-CPR”, “4-HPPA”, “4-HPAA”, “3,4-DHPAA” and “demethylase-CPR” recited in claim 40 render claims 2 and 40 indefinite. The undefined abbreviations should be spelled out upon their first occurrence.
Claim 3 recites the limitation "the nucleoside" in line 1. There is insufficient antecedent basis for this limitation in the claim. Claim 3 depends from claim 2 which depends from claim 1. None of claims 1-3 recite a nucleoside; hence, the limitation lacks antecedent basis. Claim 4 depends from claim 3 but does not resolve the indefiniteness; hence, claims 3-4 are rejected under 35 U.S.C. 112(b) as being indefinite.
Claim 3 recites the limitation "the nucleotide glycoside" in line 1. There is insufficient antecedent basis for this limitation in the claim. Claim 3 depends from claim 2 which depends from claim 1. None of claims 1-3 recite a nucleotide glycoside; hence, the limitation lacks antecedent basis. Claim 4 depends from claim 3 but does not resolve the indefiniteness; hence, claims 3-4 are rejected under 35 U.S.C. 112(b) as being indefinite.
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 1 recites the broad recitation “a glycosyl transferase”, and the claim also recites “(UGT)” which is the narrower statement of the range/limitation.
Claim 13 recites the broad recitation “has a specificity towards nororipavine which at least 50% higher”, and the claim also recites “such as at least 75% higher” and “such as at least 90% higher” which are the narrower statements of the range/limitation.
Claim 16 recites the broad recitation “has a specificity towards oripavine which at least 50% higher”, and the claim also recites “such as at least 75% higher” and “such as at least 90% higher” which are the narrower statements of the range/limitation.
Claim 40 recites the broad recitation “a 5-enolpyruvylshikimate-3-phosphate (EPSP) synthase”, and the claim also recites “(aro1)” which is the narrower statement of the range/limitation.
Claim 40 recites the broad recitation “a prephenate dehydrogenase”, and the claim also recites “(Tyr1)” which is the narrower statement of the range/limitation.
Claim 96 recites the broad recitation “culturing a cell culture... to produce the oripavine glycoside and/or nororipavine glycoside”, and the claim also recites “optionally deglycosylating the oripavine glycoside and/or nororipavine glycoside into an oripavine aglycone and/or nororipavine aglycone” and “optionally recovering and/or isolating the oripavine glycoside and/or nororipavine glycoside and/or the oripavine aglycone and/or nororipavine aglycone” which are the narrower statements of the range/limitation.
The claims 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.
Regarding claim 49, the phrase "an amino acid sequence which has at least 70%, identity to a UGT comprised in anyone of SEQ ID NO: 92" renders the claim indefinite because a) “anyone” does not mean the same thing as “any one”, b) there is a misplaced comma, and c) “to a UGT comprised in any one of” followed by a single SEQ ID NO: 92 is indefinite. The phrase should be replaced with “an amino acid sequence which has at least 70%[[,]] identity to
Claim 96 recites the limitation "the host cell" in line 2. There is insufficient antecedent basis for this limitation in the claim. Claim 96 depends from claim 1 and neither claim 1 nor 96 recite a host cell; hence, the limitation lacks antecedent basis. Appropriate correction is required.
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 pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], 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.
Claim 49 is rejected 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.
Claim 49 recites “wherein the UGT comprises an amino acid sequence which has at least 70%, identity to a UGT comprised in anyone of SEQ ID NO: 92”; however, claim 49 depends from claim 39 which depends from claim 1 which recites “wherein the UGT comprises an amino acid sequence which has at 70% identity to the UGT comprised in SEQ ID NO: 92”; hence, claim 49 does not further limit the subject matter of the claim upon which it depends because the limitation of claim 49 is already set forth in claim 1. Applicant may cancel the claim, amend the claim to place the claim in proper dependent form, rewrite the claim in independent form, or present a sufficient showing that the dependent claim complies with the statutory requirements.
Allowable Subject Matter
The subject matter of claims 1-6, 9, 13, 16, 25-26, 29-31, 39-40, 49, 73, 77, 94 and 96 are novel and non-obvious over the prior art as no reference or combination of references discloses or makes obvious the production of oripavine glycosides and/or nororipavine glycosides with an oripavine acceptor and/or nororipavine acceptor, a glycosyl donor, and a glycosyl transferase (UGT) comprising an amino acid sequence with ≥70% identity to SEQ ID NO: 92 to thereby produce the oripavine glycoside and/or nororipavine glycoside.
The closest prior art is Carvalho et al., WO 2021/069714 (Foreign Patent Document cite 2, IDS 10/23/2023; herein “Carvalho”) and Milne et al., WO 2020/239784 (Foreign Patent Document cite 1, IDS 10/23/2023; herein “Milne”).
Carvalho teaches genetically modified organisms and methods for producing oripavine and/or nororipavine comprising converting thebaine to oripavine and converting oripavine to nororipavine (Abst.) wherein the production method comprises using demethylases and genes of pathways recited in instant claim 40 [0111-120]. Carvalho does not disclose, suggest or imply glycosylating the produced oripavine or nororipavine and does not disclose a glycosyl transferase (UGT) comprising an amino acid sequence with ≥70% identity to SEQ ID NO: 92.
Milne teaches genetically modified organisms and methods for producing glycosylated cannabinoids (Abst.) wherein the glycosyl transferase is the UGT comprising amino acid SEQ ID NO: 187, which is 96.2% identical to instant SEQ ID NO: 92 ([0082-83], [0085], [0097]). Milne does not disclose, suggest or imply that the glycosyl transferase of SEQ ID NO: 187 can be used for the glycosylation of any compound other than cannabinoids and provides no basis for employing the glycosyl transferase of SEQ ID NO: 187 to glycosylate benzylisoquinoline compounds such as oripavine or nororipavine.
Hence, although the prior art teaches the production of oripavine and/or nororipavine in genetically modified host organisms (in Carvalho, for instance) and the glycosylation of cannabinoids with a glycosyl transferase (UGT) comprising an amino acid sequence with ≥70% identity to SEQ ID NO: 92 (in Milne, for instance), no prior art or combination of prior art discloses or makes obvious the glycosylation of oripavine and/or nororipavine in a genetically modified host organism with a glycosyl transferase comprising an amino acid sequence with ≥70% identity to SEQ ID NO: 92; thus, the subject matter of claims 1-6, 9, 13, 16, 25-26, 29-31, 39-40, 49, 73, 77, 94 and 96 is novel and non-obvious over the prior art.
Conclusion
Claims 1-6, 9, 13, 16, 25-26, 29-31, 39-40, 49, 73, 77, 94 and 96 are rejected but comprise subject matter which is allowable upon the resolution of the claim objections and rejections under 35 U.S.C. 112 set forth in this Office action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Trent R Clarke whose telephone number is (571)272-2904. The examiner can normally be reached M-F 10-7 MST.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Melenie Gordon can be reached at 571-272-8037. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/TRENT R CLARKE/ Examiner, Art Unit 1651
/DAVID W BERKE-SCHLESSEL/ Primary Examiner, Art Unit 1651