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
The present application is a “bypass” application of PCT/KR2022/010607 (filed on 07/20/2022) and claims priority to Korean applications KR10-2022-0088719 (filed on 07/19/2022) and KR10-2021-0096309 (filed on 07/22/2021).
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Claim Status
Claims 1-11 are currently pending and have been examined on their merits.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 01/19/2024 is in compliance with the provisions of 37 C.F.R. 1.97. All references cited in this IDS have been fully considered.
Drawings
The drawings are objected to for the following reasons.
FIG. 2 improperly presents partial views. Partial views must be identified by the same number followed by a capital letter (37 CFR 1.84(u)(1)). Accordingly, FIG. 2 should be separated into FIG. 2A and FIG. 2B.
FIGS. 3A, 6A, 6C, 7C, 8A, 8B, 10A, and 10B are not presented in sufficient quality to be readable when reproduced. Moreover, the text size of the text in these figures is smaller than the minimum height required by the Drawing Standards (37 CFR 1.84(l) and 37 CFR 1.84(p)(3)).
FIG. 5D, 10C, 11A, 11B, 11C, and 11D contain text which is in insufficient quality to be readable when reproduced (37 CFR 1.84(l)).
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
Claim 3 is objected to because the abbreviation “KCTC” should be fully defined when first used in the claims. For example, the claim may be amended to read “…a strain deposited at the Korean Collection for Type Cultures (KCTC) under accession number KCTC 14592BP”.
Claims 8-11 are objected to as being dependent upon a rejected base claim but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims for the reasons discussed below.
Claim Rejections - 35 USC § 112
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.
Claims 3 and 11 are rejected under 35 U.S.C. 112(a), as failing to comply with the enablement requirement.
The claims contain subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
The specification lacks complete deposit information for the deposit of the following microorganisms:
Yarrowia lipolytica KCTC 14592BP; and
Yarrowia lipolytica KCTC 14980BP.
Because it is not clear that the properties of these strains are known and publicly available or can be reproducibly isolated from nature without undue experimentation and because the best mode disclosed by the specification requires the use of this specific strain, a suitable deposit for patent purposes is required.
It is noted that the deposited strains were accepted on June 2, 2021, and May 19, 2022, respectively.
If the deposit has been made under the provisions of the Budapest Treaty, the deposit requirement may be fulfilled by filing an affidavit or declaration by applicants or assignees or a statement by an attorney of record who has authority and control over the conditions of the deposit over his or her signature and registration number averring that:
the deposit was made under the Budapest treaty and “all restrictions imposed by the depositor on the availability to the public of the deposited material will be irrevocably removed upon the granting of the patent”.
This requirement is necessary when deposits are made under the provisions of the Budapest Treaty as the Treaty leaves this specific matter to the discretion of each State.
If the deposits have not been made under the provisions of the Budapest Treaty, then in order to certify that the deposits comply with the criteria set forth in 37 CFR §1.801-1.809, assurances regarding availability and permanency of deposits are required. Such assurance may be in the form of an affidavit or declaration by applicants or assignees or in the form of a statement by an attorney of record who has the authority and control over the conditions of deposit over his or her signature and registration number averring that:
“during the pendency of this application, access to the deposits will be afforded to the Commissioner upon request”;
“all restrictions upon the availability to the public of the deposited biological material will be irrevocably removed upon the granting of a patent on this application”;
“the deposits will be maintained in a public depository for a period of at least thirty years from the date of the deposit or for the enforceable life of the patent or for a period of five years after the date of the most recent request for the furnishing of a sample of the deposited biological material, whichever is longest”; and
“the deposits will be replaced if they should become non-viable or non-replicable”.
As a possible means for completing the record, applicant may submit a copy of the contract with the depository for deposit and maintenance of each deposit.
If the deposit was made after the effective filing date of the application for patent in the United States, a verified statement is required from a person in a position to corroborate that the cell line described in the specification as filed is the same as that deposited in the depository. Corroboration may take the form of a showing of a chain of custody from applicant to the depository coupled with corroboration that the deposit is identical to the biological material described in the specification and in the applicant's possession at the time the application was filed.
Applicant's attention is directed to In re Lundak, 773 F.2d. 1216, 227 USPQ 90 (CAFC 1985) and 37 CFR § 1.801-1.809 for further information concerning deposit practice.
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.
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 1-2 and 4-7 are rejected under 35 U.S.C. 103 as being unpatentable over Han et al. (Journal of Applied Microbiology, 2020, Vol. 130, pages 1981-1992; cited in IDS filed on 01/19/2024) in view of Kodama et al. (US 2009/0325247 A1).
Han teaches that ceramides are sphingolipids composed of a sphingoid base and fatty acid moiety bound by an amide linkage (p. 1981, left col., par. 1). In eukaryotes, ceramides are synthesized through the sphingolipid biosynthetic pathway (p. 1982, left col., par. 2). The oleaginous yeast Yarrowia lipolytica is one of the promising hosts for sphingolipid production as this species is also a preferred microorganism for the production of lipid-derived oleochemicals, has been approved to be safe, and has unique features such as the ability to grow on hydrophobic substrates (p. 1982, right col., par. 1). Fig. 1 demonstrates the sphingolipid metabolism in Yarrowia lipolytica.
Regarding claim 1, Han teaches the generation of modified Y. lipolytica strains for the purpose of enhancing production of tetraacetylphytosphingosine (TAPS)(abstract). Specifically, Han teaches the generation of a litany of genetically modified Yarrowia lipolytica strains including Po1g, CE0, CE1, CE1-1, CE2, CE2-2, CE3, CE3-1, CE4, CE5, CE6, and CE56 (p. 1984, Table 1). LCB4 plays a key role in the accumulation of sphingolipids in yeasts and to improve TAPS production and in order to exploit this, Han generated a LCB4 deletion mutant Y. lipolytica strain (p. 1990, left col., par. 3).
Therefore, although Han teaches a Yarrowia lipolytica mutant strain, it does not teach the strain in which a SUR2 gene is deleted or expression thereof is suppressed in a Y. lipolytica strain.
Kodama et al. provides motivation to perform this deletion by teaching “abolishing the expression of the yeast sphinganine C4-hydroxylase gene (SUR2) by the transformation of a yeast cell (abstract; [0122]). Specifically, Kodama teaches that synthesis of phytosphigosine or phytoceramide is partially or completely inhibited by partially or completely abolishing the expression of SUR2 ([0068]). Kodama teaches that the expression of SUR2 can be abolished by known methods ([0127]) and “those skilled in the art can introduce desired deletions…by well-known gene engineering techniques” ([0062]).
Additionally, as discussed above, Han describes the sphingolipid metabolism in Y. lipolytica and teaches that in addition to LCB4, SUR2 is involved in conversion of dihydrosphingosine (Fig. 1A).
Thus, because Han teaches genetic modification of Y. lipolytica including deletion of genes involved in the sphingolipid metabolism pathway can result in improved production of desired metabolites (in Han’s case, TAPS), and because Kodama teaches that yeasts can have the SUR2 deletion, it would have been obvious to have tried deletion of SUR2 on Y. lipolytica. It would have been particularly obvious to have performed this precise deletion because (1) Han teaches Y. lipolytica as one of the promising hosts for sphingolipid production and (2) Han identifies SUR2 as being important for sphingolipid metabolism (as the only other identified gene to convert dihydrosphingosine) and (3) because Kodama teaches that this particular deletion in yeast can promote efficient synthesis of sphingosine and/or ceramide ([0068]). There would have been a reasonable expectation of success because (1) Han identifies SUR2 as being an active participant in the Y. lipolytica sphingolipid pathway and (2) Kodama teaches that deletion of SUR2 is within the skill of one of ordinary skill and involves the use of well-known gene engineering techniques. This obviousness is based upon the “Some Teaching, Suggestion, or Motivation in the Prior Art That Would Have Led One of Ordinary Skill To Modify the Prior Art Reference or To Combine Prior Art Reference Teachings To Arrive at the Claimed Invention” rationale set forth in KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398, 415-421, 82 USPQ2d 1385, 1395-97 (2007). See MPEP 2143(I)(G).
Accordingly, it would have been obvious to have arrived at a Yarrowia lipolytica mutant strain in which a SUR2 gene is deleted or expression thereof is suppressed and claim 1 is therefore obvious over Han in view of Kodama.
Regarding claim 2, as discussed above, Han in view of Kodama renders obvious a Y. lipolytica strain in which SUR2 is deleted or expression thereof is suppressed. Although Han does not specifically teach the gene sequence of SUR2 in Y. lipolytica, this DNA sequence is inherent to the genome of Y. lipolytica. Accordingly, because Han in view of Kodama renders obvious suppression of SUR2 in Y. lipolytica, is also renders obvious the instant claim.
Regarding claim 4, as discussed above, Han in view of Kodama renders obvious a Y. lipolytica strain in which SUR2 is deleted or expression thereof is suppressed. The enhanced secretion of dihydrosphingosine or glucosylceramide flows directly from suppression of SUR2. Accordingly, the property recited in this claim is inherent to the obvious composition. Han demonstrates this phenomenon by showing that SUR2 is involved in the conversion of dihydrosphingosine into phytosphingosine (Fig. 1A).
Regarding claim 5, as discussed above, Han in view of Kodama renders obvious the Y. lipolytica mutant strain according to claim 1.
Han teaches that mutant Y. lipolytica strains are cultured in yeast extract-peptone-dextrose (YPD) medium and then each culture was transferred to a 500-ml baffled flask with 50 ml of Y-TAPS medium (p. 1984, right col., par. 3).
Therefore, because Han teaches a method of producing TAPS comprising culturing a Y. lipolytica mutant strain and because for the reasons discussed above, it would have been obvious to have overproduced dihydrosphingosine by shunting the SUR2 pathway, it would similarly be obvious to have arrived at a method of producing dihydrosphingosine comprising culturing the Y. lipolytica mutant strain according to claim 1 in a medium.
Regarding claim 6, for the reasons discussed above, Han in view of Kodama renders obvious culturing Y. lipolytica in Y-TAPS. Y-TAPS comprises glycerol as a carbon source (p. 1984, right col., par. 3).
Regarding claim 7, as discussed above, Han in view of Kodama renders obvious the method of claim 5. The cell surface secretion of dihydrosphingosine or glucosylceramide onto a cell surface by means of lipid droplets without additional acetylation process flows naturally from the SUR2 deletion rendered obvious by Han in view of Kodama. Accordingly, for the reasons discussed above, the claim is obvious over Han in view of Kodama.
Therefore, for the reasons discussed above, claim 7 is obvious over Han in view of Kodama.
Citation of Pertinent Prior Art
A prior art rejection has not been made over claims 3 and 8-11.
With respect to claim 3, although the prior art renders obvious arriving at a generic Y. lipolytica strain in which a SUR2 gene is deleted or expression thereof is suppressed, the prior art does not teach or suggest the specific mutant strain deposited under Accession number KCTC 14592BP.
With respect to claims 8-11, although Han in view of Kodama renders obvious a Y. lipolytica strain in which a SUR2 gene is deleted or expression thereof is suppressed, neither Han nor Kodama teach or suggest also deleting an SLD1 gene encoding Δ8 desaturase. Claims 9-10 describe the gene sequence of SLD1 and the specific glucosylceramide produced by the double-deletion strain. Claim 11 recites a specific strain not taught or suggested by the prior art.
Conclusion
No claim is allowed.
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/GRANT C CURRENS/Examiner, Art Unit 1651
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