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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 2/23/2026 has been entered.
All previous rejection not reiterated in this office action are withdrawn.
Claims 1-3, 5, 6, 10, 11, 22, 27, 29, 42, 66, 74, 79, 83, 86, 90, 92, 94 and 100 are pending. Claims 2, 3, 5, 6, 10, 22, 27, 42, 66, 74, 83, 94 and 100 are withdrawn. Claims 1, 11, 29, 79, 86, 90 and 92 are currently under examination.
Response to Amendment
The amendment to the claims filed on 2/23/2026 does not comply with the requirements of 37 CFR 1.121(c) because the claim status of claim 27 is incorrect. Claim 27 should have the status of “withdrawn-currently amended” because the subject matter directed to protein having siderophore receptor protein activity is not elected for examination. Amendments to the claims filed on or after July 30, 2003 must comply with 37 CFR 1.121(c) which states:
(c) Claims. Amendments to a claim must be made by rewriting the entire claim with all changes (e.g., additions and deletions) as indicated in this subsection, except when the claim is being canceled. Each amendment document that includes a change to an existing claim, cancellation of an existing claim or addition of a new claim, must include a complete listing of all claims ever presented, including the text of all pending and withdrawn claims, in the application. The claim listing, including the text of the claims, in the amendment document will serve to replace all prior versions of the claims, in the application. 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by using one of the following identifiers in a parenthetical expression: (Original), (Currently amended), (Canceled), (Withdrawn), (Previously presented), (New), and (Not entered).
(1) Claim listing. All of the claims presented in a claim listing shall be presented in ascending numerical order. Consecutive claims having the same status of “canceled” or “not entered” may be aggregated into one statement (e.g., Claims 1–5 (canceled)). The claim listing shall commence on a separate sheet of the amendment document and the sheet(s) that contain the text of any part of the claims shall not contain any other part of the amendment.
(2) When claim text with markings is required. All claims being currently amended in an amendment paper shall be presented in the claim listing, indicate a status of “currently amended,” and be submitted with markings to indicate the changes that have been made relative to the immediate prior version of the claims. The text of any added subject matter must be shown by underlining the added text. The text of any deleted matter must be shown by strike-through except that double brackets placed before and after the deleted characters may be used to show deletion of five or fewer consecutive characters. The text of any deleted subject matter must be shown by being placed within double brackets if strike-through cannot be easily perceived. Only claims having the status of “currently amended,” or “withdrawn” if also being amended, shall include markings. If a withdrawn claim is currently amended, its status in the claim listing may be identified as “withdrawn—currently amended.”
(3) When claim text in clean version is required. The text of all pending claims not being currently amended shall be presented in the claim listing in clean version, i.e., without any markings in the presentation of text. The presentation of a clean version of any claim having the status of “original,” “withdrawn” or “previously presented” will constitute an assertion that it has not been changed relative to the immediate prior version, except to omit markings that may have been present in the immediate prior version of the claims of the status of “withdrawn” or “previously presented.” Any claim added by amendment must be indicated with the status of “new” and presented in clean version, i.e., without any underlining.
(4) When claim text shall not be presented; canceling a claim.
(i) No claim text shall be presented for any claim in the claim listing with the status of “canceled” or “not entered.”
(ii) Cancellation of a claim shall be effected by an instruction to cancel a particular claim number. Identifying the status of a claim in the claim listing as “canceled” will constitute an instruction to cancel the claim.
(5) Reinstatement of previously canceled claim. A claim which was previously canceled may be reinstated only by adding the claim as a “new” claim with a new claim number.
For purpose of compact examination, applicant is given a time period same as the time period for filing a response to the current office action to correct the status of the claim.
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.
Claim 11 is 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 11 recites “wherein the protein having ABC transporter permease activity has an enzymatic activity categorized within the enzymatic class EC 7.6.2.2 of at least one database” renders the claim indefinite because “EC 7.6.2.2” is an enzyme entry in a number of databases and encompasses different types of ABC transporter proteins. Prior to the filing of present application, there are many different enzymes from different organisms, and database entries changes over time. It is unclear which database the claim is referring to.
The following is a quotation of the first paragraph 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 the first paragraph of pre-AIA 35 U.S.C. 112:
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.
Claim 11 is 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 applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
MPEP 608.01 (p) states “An application as filed must be complete in itself in order to comply with 35 U.S.C. 112. Material nevertheless may be incorporated by reference. An application for a patent when filed may incorporate "essential material" by reference to (1) a U.S. patent, or (2) a U.S. patent application publication, which patent or patent application publication does not itself incorporate such essential material by reference. See 37 CFR 1.57(d).
"Essential material" is defined in 37 CFR 1.57(d) as that which is necessary to (1) provide a written description of the claimed 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 set forth the best mode contemplated by the inventor of carrying out the invention as required by 35 U.S.C. 112(a); (2) describe the claimed invention in terms that particularly point out and distinctly claim the invention as required by 35 U.S.C. 112(b); or (3) describe the structure, material, or acts that correspond to a claimed means or step for performing a specified function as required by 35 U.S.C. 112(f). In any application that is to issue as a U.S. patent, essential material may only be incorporated by reference to a U.S. patent or patent application publication.”
In the instant case, the protein having ABC transporter permease activity has enzymatic activity categorized within the enzymatic class EC 7.6.2.2. of at least one database is the essential material required for the engineered cell for producing a cannabinoid or derivative. However, the specification does not describe the enzymatic activity that is required for engineering the cell for producing a cannabinoid. Therefore, claim 11 is rejected under 112 (a) for improper incorporation of essential material by reference to databases.
Claim Rejections - 35 USC § 103
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 (i.e., changing from AIA to pre-AIA ) 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.
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.
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.
Claim(s) 1, 11, 79, 86, 90 and 92 is/are rejected under 35 U.S.C. 103 as being unpatentable over Kayser (US 11,674,126), in view of Sayre (US 11,773,402) and Lubelski et al (Microbiology and Molecular Biology Reviews, Sept. 2007, vol.71, no.3, pages 463-47).
The elected species of claim 1 is drawn to an engineered cell for producing a cannabinoid comprises the combination of i) express an exogenous nucleic acid sequence encoding an olivetol synthase; ii) express and exogenous nucleic acid encoding an olivetolic acid cyclase; iii) express an exogenous nucleic acid sequence encoding a prenyltransferase; and iv) express one or more exogenous nucleic acid sequence or overexpress one or more endogenous genes encoding a protein a protein having an ABC transporter permease activity.
Kayser teaches a method for recombinant production of cannabigerolic acid in a host organism comprising introducing into a host organism a nucleic acid that encodes a heterologous nucleic acid sequence encoding a modified prenyltransferase (col 5, lines 34-40). Kayser teaches a preferred embodiment is that the host organism further comprises at least 2 or 3 sequences i) hexanoyl-CoA synthase; and ii) olivetol synthase and iii) olivetolic acid cyclase (col.13, lines 1-12). Kayser teaches the host organism may be prokaryotic and eukaryotic cells including bacterial cells that may be handled using gene technology, including Escherichia coli (col.5, lines 52-60, col.6, line 3, and line 32).
However, Kayser does not teach the host organism further comprises a ABC transporter permease activity.
Sayre teaches a method of producing cannabinoids including expressing ABC transporters in host organism to actively transport cannabinoid across the cell membrane into the surrounding media, wherein the preferred ABC transporter is human multi-drug transporter (col.26, line 14-21). Although Sayre gives examples of synthesizing heterologous cytosolic CBDA synthase in plant cells, Sayre also teaches the host cell may be prokaryotes such as E. coli (col. 34, line 54-55).
Lubelski teaches distribution and physiology of ABC transporters contributing to multidrug resistance in bacteria (title). Lubelski teaches ABC superfamily comprises transporters involved in either uptake or secretion of compound from bacteria (page 465, 1st col., 3rd paragraph). Lubelski teaches E. coli contains five putative ABC transporter MDR-like transporters (page 471, 2nd col., 2nd paragraph).
It would have been obvious to ordinary skilled in the art that expressing an ABC transporter in a host organism would actively transport recombinantly made cannabinoid in a host cell to across the cell membrane into surrounding media based on the teaching from Sayre. The ordinary skilled in the art would thus be motivated to express an exogenous ABC transporter permease in addition to olivetol synthase, olivetolic acid cyclase and prenyltransferase as claimed in claim 1 to make purifying process for cannabinoid easier because the ordinary skilled in the art can continuously collecting media to obtain cannabinoid. The ordinary skilled in the art would have reasonable expectation of success to additionally introducing a nucleic acid encoding ABC transporter permease into the host organism taught by Kayser following combined teaching from Kayser and Sayre, or increase the expression of E.coli endogenous ABC transporter as discussed in Lubelski. Therefore, the claimed invention of claim 1 would have been prima facie obvious to an ordinary skilled in the art at the time the application was filed.
Regarding claim 11, since the claim does not specify what enzymatic activity of EC 7.6.2.2 is the claim referring to, the ABC transporter taught by Sayre and Lubelski meets this limitation because it facilitate the cannabinoid transport outside the cell (col.26, line 14-16).
Regarding claim 79, Kayser teaches promoter sequences in the host organism can be modified, or activators or repressors can be introduced into the nucleotide sequences (col.4, lines 3-5).
Regarding claim 86, Kayser teaches the preferred recombinant organism is a microbial organism including E. coli (col.6, line 3, and line 32).
Regarding claim 90, Kayser teaches that the prenyltransferase is modified to have at least one amino acid position changed by substitution, deletion or insertion (col.9, line 26-32).
Regarding claim 92, Kayser gives example of producing cannabigerolic acid (CBGA) in example 1 (col.18, line 61-63).
Claim(s) 29 is/are rejected under 35 U.S.C. 103 as being unpatentable over Kayser and Sayre and Lubelski, as applied to claim 1 above, and further in view of Luo et al (Nature, 2019, Vol. 567, pages 123-127 with extended data) and Milke et al (Microbial Cell Factories, 2019, Vol. 18, no.71, pages 1-12). This rejection is rewritten to address the amendment.
The teaching from Kayser and Sayre has been discussed above. However, neither references teaches said engineered cell is modified for a disruption or downregulation of a repressor of transcription of one or more genes required for fatty acid beta oxidation or an upper regulator of fatty acid biosynthesis.
Luo et al. teaches complete biosynthesis of cannabinoids and their unnatural analogues in yeast, the engineered biosynthetic pathway for synthesis of cannabinoids requires the starting material Malonyl-CoA (Figure 1 and legend).
Milke et al. teaches engineering of bacterium Corynebacterium glutamicum for producing plant polyphenol synthesis by identifying and abolishment of catabolic phenylpropanoid pathway. Milke et al. teach low intracellular availability of malonyl-CoA provided by the central metabolism could be identified as major bottleneck impeding higher product titers (bridging paragraph of page 1 and 2). Milke et al. teach engineering mutant fasO motif results in increased intracellular malonyl Co-A (Figure 4 and legend).
It would have been obvious to an ordinary skilled in the art that the availability of malonyl-CoA is important for producing cannabinoids based on the teaching of Luo. The ordinary skilled in the art would recognize that mutating genes in fatty acid synthesis or oxidation pathway would alter intracellular malonyl-CoA production based on the teaching from Milke et al. The ordinary skilled in the art would thus be motivated to disrupt or downregulate the expression of enzymes that depletes the intracellular availability of malonyl-CoA, which is required for cannabinoid production as claimed. Downregulating such enzyme in a bacterial organism engineered to produce cannabinoid rendered obvious by combined teaching from Kayser, Sayre and Lubelski would have reasonable expectation of success following combined teaching from Kayser, Sayre, Lubelski, Luo and Milke et al. Therefore, the claimed invention of claim 29 would have been prima facie obvious to an ordinary skilled in the art at the time the application was filed.
Response to Arguments
Applicant argues that the cited references addresses different technical problems, and cannot be combined. Applicant states that Kayser is directed to the biosynthesis of cannabinoids in engineered cells but does not teach the use of ABC transporter; Sayre discusses general expression platforms and host organisms but does not address cannabinoid transport, intracellular accumulation, metabolic toxicity, or the role of ABC transporters in cannabinoid biosynthesis; Lubelski is a review article that focused on MDR transport system in bacteria, particularly the role of ABC transporters in antibiotic resistance phenotypes, and does not address cannabinoid production, malonyl-CoA derived metabolic pathways, or metabolic engineering strategies for improving secondary metabolite yields. Applicant argues that the OA does not explain why a person of ordinary skilled in the art (OSITA) would look to a multidrug resistance review article to solve problems associated with cannabinoid production in engineered cells.
Applicant's arguments filed on 2/23/2026 have been fully considered but they are not persuasive. In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). Applicant’s characterization of the teaching of each reference is incomplete, especially Sayre, who teaches a method of producing cannabinoids including expressing ABC transporters in host organism to actively transport cannabinoid across the cell membrane into the surrounding media, wherein the preferred ABC transporter is human multi-drug transporter (col.26, line 14-21). This is not merely teaching an expression system for expressing an ABC transporter in a host cell, but also teaches that it transports cannabinoid across the cell membrane into surrounding media. Contrary to Applicant’s assertion, Sayre also teaches that a human multidrug transporter may be expressed in a plant cell suspension, whereas Lubelski teaches the existence of multidrug transporter in bacterial cell. The combination of Kayser, Sayre and Lubelski thus teaches and every element of the claim. In response to applicant's argument that Kayser, Sayre and Lubelski is unrelated art, it has been held that a prior art reference must in the field of the inventor’s endeavor, not necessarily analogous to each other for determining obviousness. In the present case, the rejection set forth above clearly explained the reason for combining Kayser, Sayre and Lubelski (see discussion above).
Applicant further argues that structural classification of ABC transporter permease activity in E. coli as sufficient to meet the claim limitation. Applicant argues that Lubelski underscores the unpredictability of ABC transporter function rather than providing guidance that would support their use in a cannabinoid producing engineered cell to improve cannabinoid production.
This argument is not persuasive because the claimed invention is directed to a product, which is characterized by its structure, the alleged improvement for cannabinoid production is not part of the claim limitation.
Applicant argues that Lubelski’s disclosure of macrolide specific efflux transporters provides no teaching or suggestion that such transporter would recognize cannabinoids or cannabinoid intermediates; improve metabolic flux in a cannabinoid biosynthetic pathway; reduce cannabinoid-associated toxicity; or increase cannabinoid yield in an engineered microbial host. Applicant argues that the rejection lacks the required showing that a person of ordinary skill would have a reasonable expectation that the proposed combination would function for the intended purpose. Applicant further argues that Kayser and Sayre do not provide teaching or suggestion that would direct the skilled artisan to the Lubelski reference, and the combination of Kayser, Sayre and Lubelski would only be arrived after hindsight reasoning. Applicant argues that the claimed context is cannabinoid production engineered cells and the cited references do not provide the required expectation of success.
This argument is not persuasive because the claimed invention is directed to a product, which is characterized by its structure, the alleged improvement for cannabinoid production, whether such transporter would recognize cannabinoids or cannabinoid intermediates; improve metabolic flux in a cannabinoid biosynthetic pathway; reduce cannabinoid-associated toxicity; or increase cannabinoid yield in an engineered microbial host, all of which are not part of the claim limitation. Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993).
Therefore, for reason discussed in the previous rejection and set forth above, this rejection is still considered proper and thus maintained.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CELINE X QIAN whose telephone number is (571)272-0777. The examiner can normally be reached M-F (8-4:00).
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Jennifer Dunston can be reached at 571-272-2916. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/CELINE X QIAN/Primary Examiner, Art Unit 1637
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