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 claims benefit of priority to Provisional Application 62/897,174 filed on 09/06/2019 and is also a 371 of PCT/US2020/049430 filed on 09/04/2020. Therefore, for the purposes of applying prior art, the effective filing date of the instant application is 09/06/2019.
Amendments and Claim Status
In the reply filed on 03/10/2026, Applicant amended claims 1-2, 5, 10, 13, 24 and 47, canceled claims 8, 16 and 50 and added new claims 54-55.
Claims 1-3, 5, 10-11, 13, 19-21, 23-24, 38, 40, 44-45, 47 and 54-55 are currently pending.
Claim 40 remains withdrawn as it is not encompassed the elected Group/Species.
Claims 1-3, 5, 10-11, 13, 19-21, 23-24, 38, 44-45, 47 and 54-55 are under examination.
Maintained Rejections (with modification as necessitated by amendment)
Claim Rejections - 35 USC § 103
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, 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 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 1-3, 5, 10-11, 13, 19-21, 23-24, 38, 44-45, 47 and 54-55 are rejected under 35 U.S.C. 103 as being unpatentable over Noble et al. (US 20210254030 A1, 08/19/2021, with the benefit of priority to Provisional Application 62/640,384 filed on 03/08/2018) (IDS Reference of 01/16/2023) and further in view of Mookerjee et al. (US 11312979 B2, 04/26/2022, with benefit of priority to PCT/CA2018/050189 filed on 02/19/2018).
Regarding claims 1-3, 5, 10, 19-20, Noble et al. disclose a non-natural prenyltransferase comprising SEQ ID NO. 1 (Paragraph [0011]). SEQ ID NO. 1 of Noble et al. has 100% sequence identity to instant SEQ ID NO. 1. A sequence alignment of instant SEQ ID NO. 1 and SEQ ID NO. 1 of Noble et al. is attached below.
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Noble et al. further disclose:
prenyltransferase homologs and non-natural prenyltransferase variants were identified that demonstrated activity on, or improved activity on catalyzing the reaction between olivetolic acid (OLA) and geranyl diphosphate (GPP) to form the product 3-geranyl-olivetolate (cannabigerolic acid; CBGA, 3-GOLA). Described herein are a soluble prenyltransferase of SEQ ID NO: 1 and variants thereof with improved activity and/or regioselectivity. Also described herein are homologs of SEQ ID NO: 1 and variants thereof, including NphB and non-natural prenyltransferase variants of those of prenyltransferase homologs with improved activity and/or regioselectivity (Paragraph [0011]).
Noble et al. also disclose specific amino acid variations relative to SEQ ID NO. 1 include:
S49T, F121L, T124R, Q159H, Q159R, Q159S, Q159T, Q159Y, Q159A, Q159F, Q159G, Q159I, Q159K, Q159L, Q159M, Q159A, S175H, S175K, S175R, S212H, I232H, T267W, L268Y, A285Y, Y286A, Y286F, Y286L, Y286M, Y286P, Y286I, Y286T, Y286V, Q293F, Q293W, Q293H, Q293C, Q293A, Q293S, Q293V, Q293D, Q293Y, Q293E, Q293I, Q293M, Q293T, and F300K (Paragraph [0018]).
Noble et al. do not explicitly disclose a prenyltransferase comprising SEQ ID NO. 1 with Q159S, S212H, T267P and Y286V variations. However, as discussed above, Noble et al. do disclose amino acid variations relative to SEQ ID NO. 1 can include one or more variations, some of which include Q159S, S212H, T267W and Y286V.
Noble et al. do not disclose a T267P variation.
However, Mookerjee et al. disclose a cytosolic prenyltransferase enzyme represented by SEQ ID NO. 27. SEQ ID NO. 27 of Mookerjee et al. shares 50.2% sequence identity to instant SEQ ID NO. 1 and has a Proline (P) at the amino acid position corresponding to 267 of instant SEQ ID NO. 1. A sequence alignment of SEQ ID NO. 27 of Mookerjee et al. (labeled Qy) and instant SEQ ID NO. 1 (labeled Db) is provided below.
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Exemplary rationales that may support a conclusion of obviousness include simple substitution of one known element for another to obtain predictable results. See MPEP 2143(I)(B). As such, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have made the T267P substitution in the prenyltransferase of Noble et al. because it was a known substitution in a prenyltransferase as taught by Mookerjee et al. motivated by the desire to create an effective prenyltransferase as it amounts to simple substitution of one known element for another to obtain predictable results.
Regarding claims 11 and 54-55, as indicated above, Noble et al./Mookerjee et al. render obvious the claimed prenyltransferase. Characteristics of the claimed prenyltransferase, including functional characteristics, would necessarily be intrinsic to the claimed prenyltransferase which has been demonstrated as obvious over the combined prior art teachings. Therefore, the enzymatic capabilities of the claimed prenyltransferse recited within claims 11 and 54-55 are determined to be intrinsically manifested as a consequence of creating the claimed prenyltransferase as suggested by the combined prior art teachings. Further, regarding claim construction, the prenyltransferase of claims 11 and 54-55 must only be capable of the stated enzymatic functions, as claims 11 and 54-55 are product claims and not method claims and thus, no physical enzymatic action/method steps occur within the claim; rather ‘…enzymatically capable of…’ is indicating an intrinsic characteristic of the claimed prenyltransferase enzyme. Also, ‘optional’ limitations are not required limitations and are therefore not being examined at this time.
Regarding claim 13, as the prenyltransferase of combined Noble et al./Mookerjee et al. is identical to instant SEQ ID NO. 1 including the elected 4 amino acid substitutions, the prenyltransferase has 90% or greater identity to instant SEQ ID NO. 1.
Regarding claims 21 and 23, Noble et al. disclose nucleic acids encoding the non-natural prenyltransferases with one or more variant amino acids and engineered cells comprising the nucleic acids (Paragraph [0025]).
Regarding claim 24, Noble et al. disclose an engineered cell comprising an olivetolic acid pathway (Claim 51 of Noble et al.). It is noted ‘optional’ limitations are not required limitations and are therefore not being examined at this time.
Regarding claim 38, Noble et al. disclose a variety of microorganisms are suitable for incorporating the variant prenyltransferase, including bacteria and yeast (Paragraph [0131]). Optional limitations are not being examined.
Regarding claims 44 and 45, Noble et al. disclose non-natural prenyltransferase variants were identified that demonstrated activity or improved activity on catalyzing the reaction between olivetolic acid and geranyl diphosphate to form 3-geranyl-olivetolate, or 3-GOLA (Paragraph [0011]). Geranyl diphosphate reads on a substrate comprising a hydrophobic portion, olivetolic acid reads on an aromatic substrate and 3-geranyl-olivetolate reads on a prenylated aromatic compound. As the non-natural prenyltransferase variant catalyzes the reaction between olivetolic acid and geranyl diphosphate to form 3-geranyl-olivetolate, the non-natural prenyltransferase must come into contact with the two substrates.
Regarding claim 47, Noble et al. disclose the non-natural prenyltransferases can be used to catalyze the formation of 3-GOLA in engineered cells to generate high titers of the molecule (Paragraph [0012]). Thus, the contacting must occur in the cell as the reaction is occurring in the engineered cell.
USC § 103 – Response to Arguments
Applicant's arguments filed 03/10/2026 have been fully considered but they are not persuasive.
On Page 12 of Applicant’s remarks, Applicant argued that SEQ ID NO: 27 of Mookerjee et al. falls outside of the scope of the claims because the amendment to claims 1-2 requires at least 60% sequence identity and therefore there would be no motivation to look towards Mookerjee et al.
The Examiner respectfully disagrees. The Examiner did not suggest to replace the prenyltransferase of Noble et al. with the prenyltransferase of Mookerjee et al., rather, the Examiner stated it would have been obvious to have made the T267P substitution in the prenyltransferase of Noble et al. because it was a known substitution in a prenyltransferase as taught by Mookerjee et al. Thus, neither Noble et al. nor Mookerjee et al. fall outside of the scope of the claims.
Applicant further argued Mookerjee et al. do not teach or suggest any amino acid modifications to any of their prenyltransferases.
Mookerjee et al. was not utilized to teach or suggest modification to a prenyltransferase. The prenyltransferase being modified is the prenyltransferase of Noble et al. and Noble et al. specifically disclose, as discussed above, prenyltransferase homologs and non-natural prenyltransferase variants that have improved activity on catalyzing the reaction between olivetolic acid (OLA) and geranyl diphosphate (GPP) to form the product 3-geranyl-olivetolate (cannabigerolic acid; CBGA, 3-GOLA). Noble et al. further discloses specific amino acid variations. Thus, the prior art utilized to suggest modification is Noble et al., not Mookerjee et al.
Applicant went on to argue the claims as-amended require that the at least one amino acid variation increases prenyltransferase activity and Mookerjee et al. do not teach or suggest any of their prenyltransferases should be modified to increase their activities.
The limitation regarding the amino acid variation increasing the prenyltransferase activity is what the variation does, not what the variation is. Claims 1-2 are product claims, defined by the structure of the product. If the prenyltransferase of the prior art discloses the instantly claimed variations, which are what increases the activity, then the variation necessarily reads on this limitation. Nevertheless, as discussed immediately above, Noble et al. disclose prenyltransferase homologs and non-natural prenyltransferase variants that have improved activity. Additionally, it is noted that Mookerjee et al. is used specifically for their prenyltransferase sequence which comprises one of the specific substitutions instantly claimed. Mookerjee et al. is not being modified. Noble et al. is being modified.
Thus, Applicant’s arguments are not persuasive.
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 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 1-3, 5, 10-11, 13, 19-21, 23-24, 38, 44-45, 47 and 54-55 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-18 of U.S. Patent No. 11685908 B2 in view of Mookerjee et al. (US 20200283807 A1, 09/10/2020).
Although the claims at issue are not identical, they are not patentably distinct from each other because both sets of claims are drawn to a non-natural prenyltransferase, a nucleic acid encoding the non-natural prenyltransferase and an engineered cell comprising the non-natural prenyltransferase. Claim 1 of ‘908 recites a non-natural prenyltransferase based on a template of a wild type prenyltransferase that has 75% or greater identity to SEQ ID NO. 1 and at least one amino acid variation at multiple positions, including positions 159, 212, 267 and 286, wherein the variations can include Q159S, S212H, T267W and Y286V. Claim 8 of ‘908 goes on to recite three amino acid variations with one option being Q159S, S212H and Y286A or Y286V. Claims 6 and 15-18 of ‘908 recite the same limitations.
‘908 does not disclose a T267P variation.
However, Mookerjee et al. disclose a cytosolic prenyltransferase enzyme represented by SEQ ID NO. 27. SEQ ID NO. 27 of Mookerjee et al. shares 50.2% sequence identity to instant SEQ ID NO. 1 and has a Proline (P) at the amino acid position corresponding to 267 of instant SEQ ID NO. 1. Exemplary rationales that may support a conclusion of obviousness include simple substitution of one known element for another to obtain predictable results. See MPEP 2143(I)(B). As such, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have made the T267P substitution in the prenyltransferase of Noble et al. because it was a known substitution in a prenyltransferase as taught by Mookerjee et al. motivated by the desire to create an effective prenyltransferase as it amounts to simple substitution of one known element for another to obtain predictable results.
Thus, ‘908 reads on and makes obvious the instant claims.
Double Patenting – Response to Arguments
Applicant's arguments filed 03/10/2026 have been fully considered but they are not persuasive.
Applicant’s arguments regarding the claims not being prima facie obvious in view of the disclosures of Noble et al. and Mookerjee et al. are not persuasive for the reasons discussed above. Therefore, the double patenting rejection is maintained.
Conclusion
Claims 1-3, 5, 10-11, 13, 19-21, 23-24, 38, 44-45, 47 and 54-55 are rejected.
No claims are allowed.
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.
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/A.T.W./Examiner, Art Unit 1653
/SHARMILA G LANDAU/Supervisory Patent Examiner, Art Unit 1653
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