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 .
Election/Restrictions
Applicant’s election without traverse of Group I, claims 17-25 and 29 and the species of SEQ ID NO: 1 in the reply filed on 06/28/26 is acknowledged.
Claims 26-28 and 30-34 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 06/28/26.
Priority
The instant application claims benefit to PCT/EP2022/085351 and EP21214164.2 and is acknowledged. The instant claims herein are examined using the effective filing date of 12/13/2021 for the basis of any prior art rejections.
Information Disclosure Statement
The information disclosure statement(s) (IDS) submitted 06/24/24, 08/22/24, and 03/10/26 were properly filed in compliance with 37 CFR 1.97. Accordingly, the information disclosure statement(s) were considered.
Specification
The disclosure is objected to because of the following informalities: the specification refers to the drawings as “Figure” instead of “FIG.”.
Appropriate correction is required.
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
Claim Rejections - 35 USC § 112(a)
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.
Claims 17-25 and 29 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.
The written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, reduction to drawings, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the inventor was in possession of the claimed genus. See, e.g., Ariad Pharm., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1340, 94 USPQ2d 1161, 1167 (Fed. Cir. 2010); University of California v. Eli Lilly & Co., 119 F.3d 1559, 43 USPQ2d 1398 (Fed. Cir. 1997) at 1406; Juno Therapeutics, Inc. v. Kite Pharma, Inc., 10 F.4th 1330, 1337, 2021 USPQ2d 893 (Fed. Cir. 2021) ("[T]he written description must lead a person of ordinary skill in the art to understand that the inventor possessed the entire scope of the claimed invention. Ariad, 598 F.3d at 1353–54 ('[T]he purpose of the written description requirement is to ensure that the scope of the right to exclude, as set forth in the claims, does not overreach the scope of the inventor's contribution to the field of art as described in the patent specification.' (internal quotation marks omitted).").
A "representative number of species" means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus. See AbbVie Deutschland GmbH & Co., KG v. Janssen Biotech, Inc., 759 F.3d 1285, 1300, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014). The issue is whether the skilled artisan would understand inventor to have invented, and been in possession of, the invention as claimed.
Independent claim 17 (and thus the dependent claims) recite “a method for the manufacture of a composition comprising at least one santalene comprising the step of converting farnesyl pyrophosphate into at least one santalene, wherein said conversion is carried out by at least one polypeptide exhibiting santalene synthase activity,wherein said at least one polypeptide comprises an amino acid sequence selected from the group consisting of: a) an amino acid sequence as shown in any of SEQ ID NO: 1, 18, 21, 22, 23, 24, 25, 26,27, or 28; b) an amino acid sequence which is at least 60%, at least 70%, at least 80%, at least 85%,at least 90%, at least 95%, at least 98% or at least 99% identical to the amino acid sequences as shown in any of SEQ ID NO: 1, 18, or 21, 22, 23, 24, 25, 26, 27, or 28; c) an amino acid sequence encoded by a nucleic acid sequence as shown in any one of SEQ ID NOs: 2 or 3 or 19; d) an amino acid sequence encoded by a nucleic acid sequence which is at least 60%, at least 70%, at least 80%, at least 85%, at least 90%, at least 95%, at least 98% or at least 99% identical to a polypeptide encoded by the nucleic acid sequence as shown in any one of SEQ ID NOs: 2 or 3 or 19; and e) an amino acid sequence of a fragment of any one of (a) to (d), said fragment encoding a polypeptide exhibiting santalene synthase activity.” Please note that the rejection below will specifically address the genus of species Applicant has elected (SEQ ID NO: 1).
Under broadest reasonable interpretation, the claim requires the an amino acid sequence with anywhere between 60-99% sequence identity to SEQ ID NO 1 that exhibits santalene synthase activity or an amino acid sequence of a fragment of, e.g., SEQ ID NO: 1. The instant claim essentially recites that any sequence with 60-99% identity to SEQ ID NO 1 as recited in (a), or a fragment of any sequence with 60-99% identity to SEQ ID NO 1 as recited in (e) that must retain its santalene synthase activity for use in producing a santalene compound. This is problematic because the specification fails to teach an art-recognized correlation between the claimed structure and function between the ability of the enzyme to perform its claimed function.
In support of the claimed genus of enzymes, the specification discloses the identification of SEQ ID NO: 1, which is disclosed to be a rice santalene synthase from O. meridionalis, a BLASTP analysis that shows the best BLAST hit as 98.4% from Oryza sativa japonica, 7 other sequences within 90% identity and that the sequence identity to known santalene synthase proteins is very limited (see pg. 29-30; example 1). Applicant also demonstrates cloning of the full length SEQ ID NO 1 into E. coli andto producehe production of beta-santalene (see examples 2-6).
As discussed above, the instant claims require the specific functional language of “exhibits santalene synthase activity”. However, Applicant fails to demonstrate the use of any amino acid sequence other than full-length SEQ ID NO 1 for the production of beta-santalene. There is no support in the specification as to the use of amino acids with 60-99% sequence identity to SEQ ID NO 1, or any fragments of amino acids having at least 60% identity to SEQ ID NO 1 for the claimed method. As such, the use SEQ ID NO 1 cannot reasonably be extrapolated and applied to support possession of the entire claimed genus of enzymes useful for production of santalene, because no one species, combination, or variant accounts for the variability amongst the claimed genus. As in Ariad, merely drawing a fence around the outer limits of a purported genus is not an adequate substitute for describing a variety of materials constituting the genus and showing that one has invented a genus and not just a species.
Furthermore, SEQ ID NO 1 is 572 amino acids long. The claim allows the protein to vary by as much as 60%, which means a difference in approximately 343 amino acids across the entire length, of the sequence, not to mention the massive genus of potential fragments of such varied sequences. Even with knowledge in the art regarding modification of amino acids, one of ordinary skill would not reasonably know, based on the disclosure provided, what structures are required for the outcome of creating an enzyme retaining santalene synthase without a recognized correlation between structure and function.
The specification, then, is considered devoid of sufficiently detailed, relevant, identifying characteristics demonstrating that Applicant was in possession of the claimed genus of superoxide dismutase enzyme fragments, i.e., additional complete or partial structures, other physical and/or chemical properties, functional characteristics coupled with a known or disclosed correlation between function and structure, or some combination thereof demonstrating possession of the claimed genus.
Claim Rejections - 35 USC § 112(b)
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 17-25, and 29 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 17 recites the limitation “a method for the manufacture of a composition”. There is insufficient antecedent basis for this limitation in the claim as there is no previous recitation of any “manufacture” in the claim. Please note that all of the dependent claims are indefinite for dependency on indefinite claim 17.
Claim 19 recites “wherein said at least one santalene is a mixture of beta-santalene and alpha-santalene with an excess of beta-santalene.” The term “excess” in claim 19 is a relative term which renders the claim indefinite. The term “excess” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. It is unclear what is encompassed by the term “excess” in the instant claim (does excess beta-santalene mean a little more than the amount of alpha-santalene? Does it mean a lot more? How much more beta-santalene would be considered to be in “excess” of alpha-santalene?). Thus, the claim is indefinite. For the purposes of compact patent prosecution, the examiner is interpreting the term “excess” to encompass any amount more than alpha-santalene, so long as more beta-santalene is produced. Note that claim 20 is also indefinite for dependency on indefinite claim 19.
Claim 20 recites the term “at least about”. The term “at least about” in the claims is indefinite because the recitation of “at least” sets a lower limit but “about” does not set a lower limit. Thus, the claim is indefinite.
Claim 29 recites the term “preferably”. The phrase "preferably" throughout the claims render the claims indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. For the purposes of compact patent prosecution, the limitations after the “preferably” language has been construed to be an optional limitation.
Claim 29 also recites the limitation “into the respective alcohol”. There is insufficient antecedent basis for this limitation in the claim as there is no previous recitation of any “respective alcohol” in the claim.
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.
First rejection
Claims 17-23, and 25 are rejected under 35 U.S.C. 103 as being unpatentable over Schalk et al (US 20110281257A1) in view of Uniprot A0A0E0D0X4 (27 May 2015; see ISR; cited in Applicant’s IDS).
Schalk teaches a method for producing β-santalene comprising a) contacting farnesyl pyrophosphate (FPP) with at least one polypeptide having β-santalene synthase activity and comprising an amino acid sequence at least 50% identical to SEQ ID NO:1 or 3 (a method of for the manufacture of a composition comprising at least one santalene comprising the step of converting farnesyl pyrophosphate into at least one santalene, wherein said conversion is carried out by at least one polypeptide exhibiting santalene synthase activity as in claim 1; see claim 1).
Schalk does not teach that the amino acid sequence is SEQ ID NO: 1.
However, Uniprot A0A0E0D0X4 discloses a terprene synthase isolated from O. meridionalis that has 100% sequence identity to instant SEQ ID NO 1 (see alignment below). Note that Applicant’s specification evidences that SEQ ID NO: 1 is a rice santalene synthase from O. meridionalis (e.g., the terpene synthase is, absent evidence to the contrary, a santalene synthase).
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Therefore, it would have been prima facie obvious to one of ordinary skill to modify the method of making santalene as taught by Schalk to arrive at the claimed invention with a reasonable expectation of success. One of ordinary skill would have been motivated to make the modification because Uniprot explicitly teaches a known sequence of terpene (i.e., santalene) synthase capable for the successful production of santalene compounds.
Regarding claim 18-19, Schalk teaches the santalene is beta-santalene (see claims, throughout). Schalk also teaches that santalene is a mixture of alpha and beta-santalene (see Fig. 1 and para 0115 and Table 1). Schalk also teaches improved/increased yield of beta-santalene in comparison to alpha-santalene can be achieved via lowering Mg2+ ions in the polypeptide suspension (see paragraph 0027). Thus, absent evidence to the contrary, the “excess of beta-santalene” as instantly claimed would be the result of routine optimization using standard laboratory techniques available at the time of filing.
Regarding claim 20-21, Schalk teaches that the polypeptide is capable of producing a mixture of sesquiterpenes wherein B-santalene represents at least 35% (which encompasses at least about 50% B-santalene as instantly claimed). Please note that generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955).
Regarding claim 22-23, Schalk teaches the conversion is in a host cell (see claims 2-3) including a plant, a prokaryote or a fungus (i.e., non-vertebrate transgenic organism; see paragraph 0036, 0039, 0072).
Regarding claim 25, Schallk teaches use of heterologous expression vector (see paragraph 0069-71; example 3).
Accordingly, the claimed invention was prima facie obvious at the time of filing, especially in the absence of evidence to the contrary.
Second rejection
Claim 24 is rejected under 35 U.S.C. 103 as being unpatentable over Schalk as applied to claim 17-23 and 25 above, and further in view of Daviet (US20140113343A1).
As discussed above, the claims were rendered prima facie obvious in view of Schalk and Uniprot.
As further discussed above, Schalk does not teach production of any cis-alpha-bergamotene or trans-beta-bergamotene (see throughout). Thus, absent evidence to the contrary, the production is substantially free of these products.
None of the references explicitly teach the composition comprises sesquithujune.
However, Daviet teaches methods of producing terpene compounds using recombinant microorganisms to produce santalene (see abstract, claims, throughout). Daviet also teaches that “cultivating a microorganism of the invention in a glucose-limited fed batch fermentation process, where the terpene synthase expressed by the microorganism is capable of catalysing the formation of the terpene compound that is intended to be produced. . .[including] sesquiterpene compounds like a-santalene, patchoulol, β-santalene, valencene, cubebol, zizaene, amorpha 4,11-diene, humulene, aristolochene, bergamotene, zingiberene, farnesene, caryophyllene, isodaucene, and sesquithujene” (see paragraph 0041).
Therefore, it would have been prima facie obvious to one of ordinary skill at the time of filing to modify the method of Schalk and Uniprot by producing sesquithujene as taught by Daviet to arrive at the claimed invention with a reasonable expectation of success. One of ordinary skill would have been motivated to make the modification because Daviet explicitly teaches that santalene/terpene synthases can be used advantageously to product sesquiterpene compounds like sesquithujene
Accordingly, the claimed invention was prima facie obvious at the time of filing, especially in the absence of evidence to the contrary.
Third rejection
Claim 29 is rejected under 35 U.S.C. 103 as being unpatentable over Schalk as applied to claim 17-23 and 25 above, and further in view of Amick et al (US20150275196A1).
As discussed above, the claims were rendered prima facie obvious in view of Schalk and Uniprot.
None of the references explicitly teach oxidizing the santalene into santalol.
However, Amick teaches the use of santalene synthases to convert farnesyl pyrophosphate to form mixtures of santalene products using cells (see abstract; throughout; see paragraphs 291-292). Amick also teaches that sesquiterpenes generated from FPP via santalene synthase, i.e., santalenes and bergamotene, can be oxidized to form sesquiterpenols, i.e., santalols and bergamotol (see paragraph 0197-198).
Therefore, it would have been prima facie obvious to one of ordinary skill at the time of filing to modify the method of Schalk by oxidizing the sesquiterpenes as taught by Amick to arrive at the claimed invention with a reasonable expectation of success. One of ordinary skill would have been motivated to make the modification because Amick explicitly teaches sesquiterpenes generated from FPP via santalene synthasecan be oxidized to advantageously form sesquiterpenols, i.e., santalols.
Accordingly, the claimed invention was prima facie obvious at the time of filing, especially in the absence of evidence to the contrary.
Conclusion
NO CLAIMS ALLOWED.
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure:
Tippmann, S., Scalcinati, G., Siewers, V. and Nielsen, J. (2016), Production of farnesene and santalene by Saccharomyces cerevisiae using fed-batch cultivations with RQ-controlled feed. Biotechnol. Bioeng., 113: 72-81
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/G.C.R./Examiner, Art Unit 1651
/THOMAS J. VISONE/Supervisory Patent Examiner, Art Unit 1672
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