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 .
Detailed Action: Election/Restrictions
Applicants’ election to prosecute Group I, claims 16-19 and 24, and SEQ ID NOs 2, 3, 29 and 36 with traverse for prosecution in the reply filed on 10/30/2025 is acknowledged. The traversal is on the grounds that “… It is requested that the search be broadened to encompass the full scope of the claimed invention upon determination that the elected species is free of art. It is believed claims 16-19 and 24 read on the elected species. Traversal is at least on the grounds that the claims have a special technical feature sufficient to have the requisite unity of invention to be considered in their entirety. In particular it was surprisingly found that particular mutations to naturally occurring santalene synthase produces flexibility and enables targeted production of beta and alpha santalenes”.
The traversal by the applicants’ is answered as follows: Applicants’ arguments have been fully considered but are not deemed persuasive to withdraw the restriction requirement. Elected Group I, claims 16-19 and 24, and SEQ ID NOs 1, 2, 3, 29 and 36 is anticipated by cited prior art, for details regarding claims interpretation see 35 U.S.C. 101; 35 U.S.C. 112(b); 35 U.S.C. 112(a); 35 U.S.C. 102 rejections below; as cited prior art indeed discloses all of the claimed polypeptides comprising SEQ ID NOs: 1-3, 29 and 36 of the instant invention (also see provided sequence alignments) and under PCT Rule 13.1 and PCT Rule 13.2 lack same or corresponding technical feature. Additionally, if the examiner finds that the national stage application lacks unity of invention under 37 CFR 1.475, the examiner may in an Office Action require the applicant in the response to that action to elect an invention to which the claims shall be restricted. Such requirement may be made before any action at the discretion of the examiner. Examiner continues to maintain that “the PCT does not provide for multiple products or methods within single application”, therefore, unity of invention is lacking with regard to multiple sequences and multiple species; see 37 CFR 1.475. 37 CFR 1.475 (d) also states: If multiple products, processes of manufacture or uses are claimed, the first invention of the category first mentioned in the claims of the application and the first recited invention of each other categories related thereto will be considered as the main invention in the claims, see PCT Article 17(3)(a) 1.47(c). 37 CFR 1.475(e) further states; the determination whether a group of invention is so linked as to form a single inventive concept shall be without regard to whether the inventions are claimed in separate claims or as alternative within a single claim.
Therefore, the technical features linking the inventions of all claims 16-30 does not constitute a special technical feature as defined by PCT Rule 13.2, as it does not define a contribution over the prior art. The results from a search of each of these inventions have different considerations with respect to the prior art, i.e., the prior art applicable to one invention would not likely be applicable to another invention; the inventions are likely to raise different non-prior art issues under 35 U.S.C. 101 and/or 35 U.S.C. 112, second paragraph, 35 U.S.C. 112, first paragraph. Burden lies not only in the search of sequence databases, U.S. patents, but also in the search for non-patent literature and foreign patents and in examination of the claim language and specification for compliance with the statutes concerning new matter, distinctness, double patenting, written description and enablement. Thus, a comphrensive search of all inventions in claims 16-30 would be a serious burden and contrary to applicants’ arguments, the requirement is still deemed proper and is therefore made FINAL.
Claims 16-30 are pending in this application, elected Group I, claims 16-19 and 24, and SEQ ID NOs 1, 2, 3, 29 and 36 reading on the elected invention is now under consideration for examination, examiner also reiterates the election is a SEQUENCE election and not a species election; and claims 20-23 and 25-30 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected inventions, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 10/30/2025.
Priority
Acknowledgment is also made of applicants’ claim for foreign priority under 35 U.S.C. 119(a)-(d). This application is 371 of PCT/EP2021/064642 filed 06/01/2021 and claims the priority date of EPO Applications: 20178333.9 filed on 06/04/2020 and 21160103.4 filed on 03/02/2021. Note elected SEQ ID NOs: 29 and 36 are only granted the priority date of EPO Application 21160103.4 filed on 03/02/2021.
Information disclosure statement
The information disclosure statements (IDS) submitted on 02/10/2023 and 03/20/2023 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the IDS statements are considered and initialed by the examiner.
Objections-Abstract/Specification
I. The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code. The specification contains hyperlinks to various site domains, for example, see, pages 2 and 50-51of the instant application. Applicants’ are required to thoroughly scrutinize the specification and delete all embedded hyperlink and/or other form of browser-executable code. See MPEP § 608.01. Appropriate correction is required.
II. The Abstract of the disclosure is objected to because, Abstract should be on a separate sheet of paper. The abstract of the disclosure is objected to because the abstract is presented as part of the first page of a WO publication. The abstract should be presented as a single sheet apart from all other bibliographic material including the information included on the first page of a WO publication. If EFS is used to submit a replacement abstract, the appropriate abstract (ABST) document code should be used for the one-page document. Correction is required. See MPEP § 608.01 (b).
Claims Objections
I. Claim 17 is objected: claim 17 recites non-elected subject-matter/SEQ ID NOs. Correction and clarification is required; furthermore, a semi-colon (;) is required in the claim to separate sub-parts d. and e. in claim 17.
II. Claim 24 is objected; claim 24 recites “… or the method of claim 16”; claim 16 is drawn to a product/polypeptide and not a method. Correction and clarification is required.
Claim Rejections: 35 USC § 112(b)
The following is a quotation of the second paragraph of 35 U.S.C. 112:
(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 16 and claims 17-19 and 24 depending therefrom are rejected under of 35 U.S.C. 112(b) or 35 U.S.C. 112, second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which applicant regards as the invention.
Regarding claim 16, recites the following phrase “characterized by the fact”, renders the claim(s) indefinite because the claim(s) include(s) elements not actually disclosed (those encompassed by “characterized”) as only partial structure is recited i.e., certain amino acid residues of SEQ ID NO: 1, remainder of the molecule/structure is not defined, thereby rendering the scope of the claim(s) unascertainable; additionally it should be noted that novelty is a determination of the office not an assertion by applicant i.e., “by the fact”. See MPEP § 2173.05(d).
Regarding claim 16, the phrase "has an increased flexibility compared to the same tertiary structure in a naturally occurring santalene synthase” renders the claim indefinite. See MPEP § 2173.05(d). Recitation of the phrase "has an increased flexibility compared to the same tertiary structure in a naturally occurring santalene synthase”, in claim 16 renders the claim indefinite and considered to be a relative term, the scope, metes and bounds of “increased flexibility” is not clear and the claim does not recite/provide a specific structure to be compared with as only partial structure is recited i.e., certain amino acid residues of SEQ ID NO: 1, remainder of the molecule/structure is not defined. Specification does not provide a standard for ascertaining the requisite property of the enzyme that shows “increased flexibility” over any undefined/unlimited wild-type polypeptide(s) having santalene synthase activity or any other metric, and one of ordinary skill in the art would not be able to reasonably determine the metes and bounds of the claim, as “increased flexibility” varies widely depending on the individual situation as well as the person making the determination and is dependent upon set of conditions defined by the individual situation. It is not clear to the examiner as to what type of and metric or property with regards to “increased flexibility” is encompassed in the above phrase. Thus, the scope of the claim is unclear. A perusal of the specification describes, some exemplary conditions i.e., “increased flexibility” and the term “increased flexibility” is defined as flexibility of the catalytic property and the product produced in the variant of a specific wild-type santalene synthase and with known structure. Claim 16 as written does not recite the specific conditions/property of the enzyme the applicants' intend to encompass the claim does not recite/provide a specific structure to be compared with as only partial structure is recited i.e., certain amino acid residues of SEQ ID NO: 1, remainder of the molecule/structure is not defined and. As such it is unclear what must be to be included within the scope of the claim. Clarification and correction is required.
Claim Rejections: 35 U.S.C. 112(d)
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 24 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 24 recites “… or the method of claim 16”; claim 16 is drawn to a product/polypeptide and not a method and dependent claim 24 does not further limit claim 16. Dependent claim 24 broadens the scope of independent claim 16.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
The U.S. Court of Appeals for the Federal Circuit indicated that although the requirements of pre-AIA 35 U.S.C. 112, 4th paragraph, are related to matters of form, non-compliance with pre-AIA 35 U.S.C. 112, 4th paragraph, renders the claim unpatentable just as non-compliance with other paragraphs of 35 U.S.C. 112 would. See Pfizer, Inc. v. Ranbaxy Labs., Ltd., 457 F.3d 1284, 1291-92, 79 USPQ2d 1583, 1589-90 (Fed. Cir. 2006) (holding a dependent claim in a patent invalid for failure to comply with pre-AIA 35 U.S.C. 112, 4th paragraph). Therefore, if a dependent claim does not comply with the requirements of 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, the dependent claim should be rejected under pre-AIA 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as unpatentable rather than objecting to the claim. See also MPEP § 608.01(n),subsection III, “Infringement Test” for dependent claims.
Claim Rejections: 35 USC § 112(a)
The following is a quotation of the first paragraph of 35 U.S.C. 112(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.
Enablement
Claims 16-19 and 24 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112, first paragraph, because the specification, while being enabling for an isolated wild-type santalene synthase comprising the amino acid sequence of SEQ ID NO: 1 and specific variants of said santalene synthase comprising the amino acid sequences of SEQ ID NOs: 2, 3, 29 and 36, does not reasonably provide enablement for any synthetic beta santalene synthase of unlimited and undefined structures characterized by the fact that the tertiary structure of the part of said synthetic beta santalene synthase that correspond to the stretch from amino acid positions 272 to position 291 of SEQ ID NO: 1 has an increased flexibility compared to the flexibility of the same tertiary structure in a naturally occurring santalene synthase (only partial structure has been provided comprising certain amino acid residues and motif; remainder of the structure is undefined; as in claim 16, 18-19 and 24); any synthetic beta santalene synthase of unlimited structures producing beta-santalene and alpha-santalene from farnesyl pyrophosphate, wherein the santalene synthase has at least 50% sequence identity to a. the amino acid positions 261 to 278, preferably position 261 to position 272, of SEQ ID NO: 2, 3, 29, 57 or 58 wherein the position corresponding to position 261 of SEQ ID NO. 2, 3, 29, 57 or 58 is an Arginine residue and the position corresponding to position 278 of SEQ ID NO: 2, 3, 29, 57 or 58 is a Proline residue and said Arginine and said Proline are used to align the two protein sequences for the sequence identity determination; or b. … or c. a combination of a. and b. above; or d. the full-length of SEQ ID NO: 1 e. a combination of any of a. to c. above with d (as in claim 17, the limitations in claim 17 are recited in the alternative forms “or”; also see claims objections, 35 U.S.C. 112(b) and 35 U.S.C. 112(d) rejections above for claims interpretation). The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and or use the invention commensurate in scope with the claim.
Factors to be considered in determining whether undue experimentation is required are summarized in In re Wands (858 F.2d 731, 8 USPQ 2nd 1400 (Fed. Cir. 1988)) as follows: (1) the quantity of experimentation necessary, (2) the amount of direction or guidance presented, (3) the presence or absence of working examples, (4) the nature of the invention, (5) the state of the prior art, (6) the relative skill of those in the art, (7) the predictability or unpredictability of the art, and (8) the breadth of the claim(s).
Claims 16-19 and 24 are so broad as to encompass: any synthetic beta santalene synthase of unlimited and undefined structures characterized by the fact that the tertiary structure of the part of said synthetic beta santalene synthase that correspond to the stretch from amino acid positions 272 to position 291 of SEQ ID NO: 1 has an increased flexibility compared to the flexibility of the same tertiary structure in a naturally occurring santalene synthase (only partial structure has been provided comprising certain amino acid residues and motif; remainder of the structure is undefined; as in claim 16, 18-19 and 24); any synthetic beta santalene synthase of unlimited structures producing beta-santalene and alpha-santalene from farnesyl pyrophosphate, wherein the santalene synthase has at least 50% sequence identity to a. the amino acid positions 261 to 278, preferably position 261 to position 272, of SEQ ID NO: 2, 3, 29, 57 or 58 wherein the position corresponding to position 261 of SEQ ID NO. 2, 3, 29, 57 or 58 is an Arginine residue and the position corresponding to position 278 of SEQ ID NO: 2, 3, 29, 57 or 58 is a Proline residue and said Arginine and said Proline are used to align the two protein sequences for the sequence identity determination; or b. … or c. a combination of a. and b. above; or d. the full-length of SEQ ID NO: 1 e. a combination of any of a. to c. above with d (as in claim 17, the limitations in claim 17 are recited in the alternative forms “or”; also see claims objections, 35 U.S.C. 112(b) and 35 U.S.C. 112(d) rejections above for claims interpretation). The scope of the claims is not commensurate with the enablement provided by the disclosure with regard to the extremely large number polypeptides and encoding polynucleotides broadly encompassed by the claims. Since the amino acid sequence of a protein encoded by a polynucleotide determines its structural and functional properties, predictability of which changes can be tolerated in a protein's amino acid sequence and obtain the desired activity requires knowledge and guidance with regard to which amino acids in the protein's sequence and the respective codons in its polynucleotide, if any, are tolerant of modification and which are conserved (i.e., expectedly intolerant to modification), and detailed knowledge of the ways in which the encoded proteins' structure relates to its function. In view of the broad breadth of the claims, the amount of experimentation required to determine the structure of all the polypeptides or the encoding polynucleotides from any plant source including variants, mutants and recombinants, the lack of guidance, working examples, and unpredictability of the art in predicting function from a polypeptide primary structure (e.g., see Whisstock et al., Q Rev Biophys. 2003 Aug; 36(3): 307-340), practicing the claimed invention would require undue experimentation. As such, the specification fails to enable the entire scope of the claimed invention.
However, in this case the disclosure is limited to an isolated wild-type santalene synthase comprising the amino acid sequence of SEQ ID NO: 1 and specific variants of said santalene synthase comprising the amino acid sequences of SEQ ID NOs: 2, 3, 29 and 36, but provides no guidance with regard to the making and using of any santalene synthase comprising said motifs including variants and mutants and having the recited catalytic activity and biochemical properties; i.e., any synthetic beta santalene synthase of unlimited and undefined structures characterized by the fact that the tertiary structure of the part of said synthetic beta santalene synthase that correspond to the stretch from amino acid positions 272 to position 291 of SEQ ID NO: 1 has an increased flexibility compared to the flexibility of the same tertiary structure in a naturally occurring santalene synthase (only partial structure has been provided comprising certain amino acid residues and motif; remainder of the structure is undefined; as in claim 16, 18-19 and 24); any synthetic beta santalene synthase of unlimited structures producing beta-santalene and alpha-santalene from farnesyl pyrophosphate, wherein the santalene synthase has at least 50% sequence identity to a. the amino acid positions 261 to 278, preferably position 261 to position 272, of SEQ ID NO: 2, 3, 29, 57 or 58 wherein the position corresponding to position 261 of SEQ ID NO. 2, 3, 29, 57 or 58 is an Arginine residue and the position corresponding to position 278 of SEQ ID NO: 2, 3, 29, 57 or 58 is a Proline residue and said Arginine and said Proline are used to align the two protein sequences for the sequence identity determination; or b. … or c. a combination of a. and b. above; or d. the full-length of SEQ ID NO: 1 e. a combination of any of a. to c. above with d (as in claim 17, the limitations in claim 17 are recited in the alternative forms “or”; also see claims objections, 35 U.S.C. 112(b) and 35 U.S.C. 112(d) rejections above for claims interpretation) or with regard to other uses. In view of the great breadth of the claims, amount of experimentation required to make the claimed polypeptides and encoding polynucleotides, the lack of guidance, working examples, and unpredictability of the art in predicting function from a polypeptide primary structure (e.g., see Whisstock et al., Q Rev Biophys. 2003 Aug; 36(3): 307-340), the claimed invention would require undue experimentation. As such, the specification fails to teach one of ordinary skill how to make and use the full scope of polypeptides and encoding polynucleotides encompassed by the claims.
While enzyme isolation techniques, recombinant and mutagenesis techniques are known, and it is not routine in the art to screen for multiple substitutions or multiple modifications as encompassed by the instant claim, the specific amino acid positions within a protein's sequence where amino acid modifications can be made with a reasonable expectation of success in obtaining the desired activity/utility are limited in any protein and the result of such modifications is unpredictable. In addition, one skilled in the art would expect any tolerance to modification for a given protein to diminish with each further and additional modification, e.g. multiple substitutions or deletions.
The specification does not support the broad scope of the claims which encompass: any synthetic beta santalene synthase of unlimited and undefined structures characterized by the fact that the tertiary structure of the part of said synthetic beta santalene synthase that correspond to the stretch from amino acid positions 272 to position 291 of SEQ ID NO: 1 has an increased flexibility compared to the flexibility of the same tertiary structure in a naturally occurring santalene synthase (only partial structure has been provided comprising certain amino acid residues and motif; remainder of the structure is undefined; as in claim 16, 18-19 and 24); any synthetic beta santalene synthase of unlimited structures producing beta-santalene and alpha-santalene from farnesyl pyrophosphate, wherein the santalene synthase has at least 50% sequence identity to a. the amino acid positions 261 to 278, preferably position 261 to position 272, of SEQ ID NO: 2, 3, 29, 57 or 58 wherein the position corresponding to position 261 of SEQ ID NO. 2, 3, 29, 57 or 58 is an Arginine residue and the position corresponding to position 278 of SEQ ID NO: 2, 3, 29, 57 or 58 is a Proline residue and said Arginine and said Proline are used to align the two protein sequences for the sequence identity determination; or b. … or c. a combination of a. and b. above; or d. the full-length of SEQ ID NO: 1 e. a combination of any of a. to c. above with d (as in claim 17, the limitations in claim 17 are recited in the alternative forms “or”; also see claims objections, 35 U.S.C. 112(b) and 35 U.S.C. 112(d) rejections above for claims interpretation) because the specification does not establish: (A) regions of the protein/polynucleotide structure which may be modified without affecting the activity of the encoded santalene synthase; (B) the general tolerance of the polypeptide and the polynucleotide encoding santalene synthase to modification and extent of such tolerance; (C) a rational and predictable scheme for modifying any amino acid residue or the respective codon in the polynucleotide with an expectation of obtaining the desired biological function; and (D) the specification provides insufficient guidance as to which of the essentially infinite possible choices is likely to be successful.
Thus, applicants’ have not provided sufficient guidance to enable one of ordinary skill in the art to make and use the claimed invention in a manner reasonably correlated with the scope of the claim broadly including polypeptides and encoding polynucleotides with an enormous number of modifications including variants, mutants and recombinants of undefined and undefined structures with the associated function. The scope of the claim must bear a reasonable correlation with the scope of enablement (In re Fisher, 166 USPQ 19 24 (CCPA 1970)). Without sufficient guidance, determination of polypeptides having the desired biological characteristics is unpredictable and the experimentation left to those skilled in the art is unnecessarily, and improperly, extensive and undue. See In re Wands 858 F.2d 731, 8 USPQ2nd 1400 (Fed. Cir, 1988).
Written Description
Claims 16-19 and 24 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112, first paragraph, as containing 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(s), at the time the application was filed, had possession of the claimed invention.
Claims 16-19 and 24 as interpreted is directed to encompass: any synthetic beta santalene synthase of unlimited and undefined structures characterized by the fact that the tertiary structure of the part of said synthetic beta santalene synthase that correspond to the stretch from amino acid positions 272 to position 291 of SEQ ID NO: 1 has an increased flexibility compared to the flexibility of the same tertiary structure in a naturally occurring santalene synthase (only partial structure has been provided comprising certain amino acid residues and motif; remainder of the structure is undefined; as in claim 16, 18-19 and 24); any synthetic beta santalene synthase of unlimited structures producing beta-santalene and alpha-santalene from farnesyl pyrophosphate, wherein the santalene synthase has at least 50% sequence identity to a. the amino acid positions 261 to 278, preferably position 261 to position 272, of SEQ ID NO: 2, 3, 29, 57 or 58 wherein the position corresponding to position 261 of SEQ ID NO. 2, 3, 29, 57 or 58 is an Arginine residue and the position corresponding to position 278 of SEQ ID NO: 2, 3, 29, 57 or 58 is a Proline residue and said Arginine and said Proline are used to align the two protein sequences for the sequence identity determination; or b. … or c. a combination of a. and b. above; or d. the full-length of SEQ ID NO: 1 e. a combination of any of a. to c. above with d (as in claim 17, the limitations in claim 17 are recited in the alternative forms “or”; also see claims objections, 35 U.S.C. 112(b) and 35 U.S.C. 112(d) rejections above for claims interpretation).
In University of California v. Eli Lilly & Co., 43 USPQ2d 1938, the Court of Appeals for the Federal Circuit has held that “A written description of an invention involving a chemical genus, like a description of a chemical species, ‘requires a precise definition, such as by structure, formula, [or] chemical name,’ of the claimed subject matter sufficient to distinguish it from other materials”. As indicated in MPEP § 2163, 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 that Applicant was in possession of the claimed genus. In addition, MPEP § 2163 states that 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.
In the instant case the scope of the instant claims encompass a genus of structures (no structural limitation) for polypeptides and the encoding polynucleotides of interest with associated function, i.e., any synthetic beta santalene synthase of unlimited and undefined structures characterized by the fact that the tertiary structure of the part of said synthetic beta santalene synthase that correspond to the stretch from amino acid positions 272 to position 291 of SEQ ID NO: 1 has an increased flexibility compared to the flexibility of the same tertiary structure in a naturally occurring santalene synthase (only partial structure has been provided comprising certain amino acid residues and motif; remainder of the structure is undefined; as in claim 16, 18-19 and 24); any synthetic beta santalene synthase of unlimited structures producing beta-santalene and alpha-santalene from farnesyl pyrophosphate, wherein the santalene synthase has at least 50% sequence identity to a. the amino acid positions 261 to 278, preferably position 261 to position 272, of SEQ ID NO: 2, 3, 29, 57 or 58 wherein the position corresponding to position 261 of SEQ ID NO. 2, 3, 29, 57 or 58 is an Arginine residue and the position corresponding to position 278 of SEQ ID NO: 2, 3, 29, 57 or 58 is a Proline residue and said Arginine and said Proline are used to align the two protein sequences for the sequence identity determination; or b. … or c. a combination of a. and b. above; or d. the full-length of SEQ ID NO: 1 e. a combination of any of a. to c. above with d (as in claim 17, the limitations in claim 17 are recited in the alternative forms “or”; also see claims objections, 35 U.S.C. 112(b) and 35 U.S.C. 112(d) rejections above for claims interpretation).
No information, beyond the characterization of an isolated wild-type santalene synthase comprising the amino acid sequence of SEQ ID NO: 1 and specific variants of said santalene synthase comprising the amino acid sequences of SEQ ID NOs: 2, 3, 29 and 36, has been provided by the applicants’, which would indicate that they had possession of the claimed genus of structures (no structural limitation) for polypeptides of interest with associated function and their encoding polynucleotides, i.e., any synthetic beta santalene synthase of unlimited and undefined structures characterized by the fact that the tertiary structure of the part of said synthetic beta santalene synthase that correspond to the stretch from amino acid positions 272 to position 291 of SEQ ID NO: 1 has an increased flexibility compared to the flexibility of the same tertiary structure in a naturally occurring santalene synthase (only partial structure has been provided comprising certain amino acid residues and motif; remainder of the structure is undefined; as in claim 16, 18-19 and 24); any synthetic beta santalene synthase of unlimited structures producing beta-santalene and alpha-santalene from farnesyl pyrophosphate, wherein the santalene synthase has at least 50% sequence identity to a. the amino acid positions 261 to 278, preferably position 261 to position 272, of SEQ ID NO: 2, 3, 29, 57 or 58 wherein the position corresponding to position 261 of SEQ ID NO. 2, 3, 29, 57 or 58 is an Arginine residue and the position corresponding to position 278 of SEQ ID NO: 2, 3, 29, 57 or 58 is a Proline residue and said Arginine and said Proline are used to align the two protein sequences for the sequence identity determination; or b. … or c. a combination of a. and b. above; or d. the full-length of SEQ ID NO: 1 e. a combination of any of a. to c. above with d (as in claim 17, the limitations in claim 17 are recited in the alternative forms “or”; also see claims objections, 35 U.S.C. 112(b) and 35 U.S.C. 112(d) rejections above for claims interpretation).
The art also teaches, even highly structurally homologous polypeptides do not necessarily share the same function and conversely functionally similar molecules do not necessarily have similar structures. For example proteins having similar structure have different activities; Witkowski et al., (Biochemistry 38:11643-11650, 1999) teaches that one conservative amino acid substitution transforms a b-ketoacyl synthase into a malonyl decarboxylase and completely eliminates b-ketoacyl synthase activity. Similarly, Wishart et al., (J. Biol. Chem., 1995, Vol. 270(10): 26782-26785) teach that a single mutation converts a novel phosphotyrosine binding domain into a dual-specificity phosphatase.
Hence, the recited genera of polypeptides and the encoding polynucleotides are interpreted to have widely variable structures, since minor changes may result in changes affecting function and no additional information correlating structure with function has been provided. Therefore, given the lack of description of representative species encompassed by the genus of polypeptides, encoding polynucleotides and modifications, the specification fails to sufficiently describe the claimed invention in such full, clear, concise, and exact terms that a skilled artisan would recognize that applicants’ were in possession of the claimed invention. Applicants’ are referred to the revised guidelines concerning compliance with the written description requirement of 35 U.S.C. 112(a) or 35 U.S.C. 112, first paragraph, published in the Official Gazette and also available at www.uspto.gov.
Claim Rejections: 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title
Claims 16-19 and 24 is rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception (i.e., a law of nature, a natural phenomenon, or an abstract idea) without significantly more. Claims 16-19 and 24 is directed to a law of nature or a natural phenomenon. Claims 16-19 and 24as interpreted are directed to any synthetic beta santalene synthase of unlimited and undefined structures characterized by the fact that the tertiary structure of the part of said synthetic beta santalene synthase that correspond to the stretch from amino acid positions 272 to position 291 of SEQ ID NO: 1 has an increased flexibility compared to the flexibility of the same tertiary structure in a naturally occurring santalene synthase (only partial structure has been provided comprising certain amino acid residues and motif; remainder of the structure is undefined; as in claim 16, 18-19 and 24); any synthetic beta santalene synthase of unlimited structures producing beta-santalene and alpha-santalene from farnesyl pyrophosphate, wherein the santalene synthase has at least 50% sequence identity to a. the amino acid positions 261 to 278, preferably position 261 to position 272, of SEQ ID NO: 2, 3, 29, 57 or 58 wherein the position corresponding to position 261 of SEQ ID NO. 2, 3, 29, 57 or 58 is an Arginine residue and the position corresponding to position 278 of SEQ ID NO: 2, 3, 29, 57 or 58 is a Proline residue and said Arginine and said Proline are used to align the two protein sequences for the sequence identity determination; or b. … or c. a combination of a. and b. above; or d. the full-length of SEQ ID NO: 1 e. a combination of any of a. to c. above with d (as in claim 17, the limitations in claim 17 are recited in the alternative forms “or”; also see claims objections, 35 U.S.C. 112(b) and 35 U.S.C. 112(d) rejections above for claims interpretation). The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception for the reasons stated below.
The “2014 Interim Guidance on Patent Subject Matter Eligibility” 79 FR 74618 (Dec. 16, 2014) directs that claims drawn to 1) a composition of matter, 2) a law of nature or a natural phenomenon and 3) lacking recitation of additional elements that make the claims directed to significantly more than a judicial exception are ineligible for patenting under 35 U.S.C. 101. See, 79 FR, page 74621 (flow chart). Nature-based compositions of matter are not directed to significantly more than a judicial exception when the claimed "naturally occurring products and some man-made products ... are essentially no different from a naturally occurring product ... that fall under the laws of nature or natural phenomena exception.” 79 FR, page 74623, left column. That is, a patent-eligible composition of matter must be "markedly different" in terms of the "product's structure, function, and/or other properties." 79 FR, page 74623, center column. Further, processes directly to isolating nature-based compositions of matter have also been found to be directed to nothing more than a judicial exception when only routine purification techniques are employed. 79 FR, page 74622, center column (e.g. isolating DNA or other nature-based products).
Here, naturally-occurring variant polypeptides of SEQ ID NO: 1 (wild-type sequence) annotated as santalene synthase, and variants comprising an amino acid substitution corresponding to amino acid residues N267S and I291V of SEQ ID NO: 1, annotated as terpinol synthase and encoding polynucleotide sequence is disclosed: see (i) Di Girolamo et al., UniProtKB/TrEMBL Accesion#A0A7S6HRZ4 having 100% sequence identity to SEQ ID NO: 1 and naturally-occurring variant UniProtKB/TrEMBL Accession# A0A7S6L0M3 having 95.8% to SEQ ID NO: 1 and comprising amino acid residue 267S of the instant application; and (ii) Chaw et al., UniProtKB/TrEMBL Accesion#A0A3S3Q284 disclose naturally-occurring variants having 92.8%-89.8% sequence identities to SEQ ID NOs: 1-3, 29 and 36 of the instant invention, comprising amino acid substitutions corresponding to N267S and I291V of SEQ ID NO: 1, annotated as terpinol synthase and encoding polynucleotide. The features of claims 16-19 and 24 is met by the reference polypeptides in the disclosed references above. Since the features of the claims are met by the structure of a polypeptides of SEQ ID NO: 1-3, 29 and 36 of the instant application and the claims do not recite additional features or elements that amount to significantly more than the judicial exception, since the structure recited in claims 16-19 and 24 is "essentially no different from a naturally occurring product” such that there is no marked difference in the "product's structure, function, and/or other properties. As such, the claims 16-19 and 24 recite patent ineligible subject matter for the reasons stated.
Examiner also takes the following position regarding claims 16-19 and 24 are directed to a composition/product; Structure and function are inseparable, and if the structure is disclosed in the art, the claim is anticipated or reads on naturally-occurring polypeptide(s) and a method of determination of the property of the claimed polypeptide(s) language in preamble is given no patentable weight i.e., “characterized by the fact…, wherein the flexibility is determined by root mean square fluctuation analysis using simulations for 500 ns for both the synthetic and the naturally occurring santalene synthase with these settings: pH 8.0, 300 K, 1 atm, water environment, ions present without substrate, and evaluation for each enzyme structure on the last 450 ns of simulation; and wherein said synthetic beta santalene synthase is further characterized by its ability to produce beta-santalene and alpha-santalene in a ratio that is equal to or greater than 1 under typical conditions suitable for the production of both these santalenes, wherein beta-santalene is (-)-p-santalene” is not given any patentable weight as the claims are directed to a product.
• The body of the claim following the preamble is a self-contained description of the structure and does not depend on the preamble for completeness.
• A preamble that describes the purpose or intended use of the claimed invention generally does not limit the claims.
• The preamble merely extols benefits or features of the claimed invention and there is no clear reliance on those benefits or features as patentably significant (e.g., preamble recites, “[a] head for a lacrosse stick which provides improved handling and playing characteristics.”).
See: MPEP 2111.02 & 2111.02(II)
II. PREAMBLE STATEMENTS RECITING PURPOSE OR INTENDED USE
The claim preamble must be read in the context of the entire claim. The determination of whether preamble recitations are structural limitations or mere statements of purpose or use “can be resolved only on review of the entirety of the [record] to gain an understanding of what the inventors actually invented and intended to encompass by the claim.” Corning Glass Works, 868 F.2d at 1257,9 USPQ2d at 1966. If the body of a claim fully and intrinsically sets forth all of the limitations of the claimed invention and the preamble merely states, for example, the purpose or intended use of the invention, rather than any distinct definition of any of the claimed invention’s limitations, then the preamble is not considered a limitation and is of no significance to claim construction. Pitney Bowes, Inc. v. Hewlett-Packard Co., 182 F.3d1298, 1305, 51 USPQ2d 1161, 1165 (Fed. Cir. 1999). See also Rowe v. Dror, 112 F.3d 473, 478, 42 USPQ2d 1550,1553 (Fed. Cir. 1997) (“where a patentee defines a structurally complete invention in the claim body and uses the preamble only to state a purpose or intended use for the invention, the preamble is not a claim limitation”); Kropa v. Robie, 187 F.2d at 152, 88 USPQ2d at 480-81 (preamble is not a limitation where claim is directed to a product and the preamble merely recites a property inherent in an old product defined by the remainder of the claim); STX LLC. v. Brine, 211 F.3d 588, 591, 54USPQ2d 1347, 1350 (Fed. Cir. 2000) (holding that the preamble phrase “which provides improved playing and handling characteristics” in a claim drawn to a head fora lacrosse stick was not a claim limitation).
During examination, statements in the preamble reciting the purpose or intended use of the claimed invention must be evaluated to determine whether the recited purpose or intended use results in a structural difference (or, in the case of process claims, manipulative difference) between the claimed invention and the prior art. In re Sinex, 309 F.2d 488, 492, 135 USPQ 302, 305(CCPA 1962) (statement of intended use in an apparatus claim did not distinguish over the prior art apparatus). If a prior art structure is capable of performing the intended use as recited in the preamble, then it meets the claim.
See also Catalina Mktg. Int’l v. Coolsavings.com, Inc.,289 F.3d at 808-09, 62 USPQ2d at 1785 (“[C]lear reliance on the preamble during prosecution to distinguish the claimed invention from the prior art transforms the preamble into a claim limitation because such reliance indicates use of the preamble to define, in part, the claimed invention.…Without such reliance, however, a preamble generally is not limiting when the claim body describes a structurally complete invention such that deletion of the preamble phrase does not affect the structure or steps of the claimed invention.” Consequently, “preamble language merely extolling benefits or features of the claimed invention does not limit the claim scope without clear reliance on those benefits or features as patentably significant.”).
Claim Rejections: 35 USC § 102 (AIA )
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 16-19 and 24 are rejected under 35 U.S.C. 102(a)(1) and 35 U.S.C. 102(a)(2) as being anticipated by (i) Chaw et al., UniProtKB/TrEMBL Accesion#A0A3S3Q284 disclose naturally-occurring variants having 92.8%-89.8% sequence identities to SEQ ID NOs: 1-3, 29 and 36 of the instant invention, comprising amino acid substitutions corresponding to N267S and I291V of SEQ ID NO: 1, annotated as terpinol synthase and encoding polynucleotide (see provided sequence alignments); and (ii) Beekwilder et al., (US 11,390,863), disclose santalene synthase having 100% sequence identity to SEQ ID NO: 1 of the instant invention, and additionally variant having 95.9% sequence identity to SEQ ID NO: 1 and comprising an amino acid substitution corresponding to amino acid residue N267S of SEQ ID NO: 1 and encoding polynucleotide sequence of the instant application (see Fig. 10-11; col. 4, lines 16-42; and provided sequence alignments), and the cited references are deemed to anticipate claims 16-19 and 24 as written and when given the broadest reasonable interpretation.
2112 [R-3] Requirements of Rejection Based on Inherency; Burden of Proof The express, implicit, and inherent disclosures of a prior art reference may be relied upon in the rejection of claims under 35 U.S.C. 102 or 103. “The inherent teaching of a prior art reference, a question of fact, arises both in the context of anticipation and obviousness.” In re Napier, 55 F.3d 610, 613, 34 USPQ2d 1782, 1784 (Fed. Cir. 1995) (affirmed a 35 U.S.C. 103 rejection based in part on inherent disclosure in one of the references). See also In re Grasselli, 713 F.2d 731, 739, 218 USPQ 769, 775 (, X7Fed. Cir. 1983).
I. SOMETHING WHICH IS OLD DOES NOT BECOME PATENTABLE UPON THE DIS-COVERY OF A NEW PROPERTY
II. INHERENT FEATURE NEED NOT BE RECOGNIZED AT THE TIME OF THE INVENTION
III. A REJECTION UNDER 35 U.S.C. 102/103 CAN BE MADE WHEN THE PRIOR ART PRODUCT SEEMS TO BE IDENTICAL EXCEPT THAT THE PRIOR ART IS SILENT AS TO AN INHERENT CHARACTERISTIC
Allowable Subject Matter/Conclusion
None of the claims are allowable.
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/GANAPATHIRAMA RAGHU/ Primary Examiner, Art Unit 1652