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
Claims 26-40, 42 and 45-49 are pending.
Priority
This action, filed on 10/19/2023, is a 371 of PCT/SG2022/050235 filed on 4/20/2022, which claims benefit to SINGAPORE 10202104047X filed on 4/20/2021. The effective filing date of the instant application is April 20, 2021.
Election/Restrictions
Applicant’s election without traverse of Group I: claims 26-40, and species, first substitution at position 200; second substitution at position 182; 13th substitution at position 176; and SEQ ID NO:16, in the reply filed on April 24, 2026 is acknowledged.
The species election requirement for Genus: second substitution position, and Genus: thirteenth substitution position, as set forth in the Office action mailed on 2/27/2026, has been reconsidered. The species election requirement is hereby withdrawn as to any claim that requires all the limitations of an elected claim. Specifically, the species election requirement of 2/27/2026 is partially withdrawn with respect to claim 27, which required an election for second substitution position and with respect to claim 39, which required an election for thirteenth substitution position. Claims 42 and 45-49 remain withdrawn from consideration because they do not require all the limitations of the elected claims.
Claims 42 and 45-49 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected inventions, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on April 24, 2026.
Claims 26-40 are under examination.
Claim
Amino Acid Position
Elected Species
Non-elected Species
Prior Art
Y/N
Sequence;
% identity;
Reference
26
Y200 to F/I/L/V/W (1st substitution)
Y
Graham/GenBank PAU49021 teaches Y200L;
and has 71% identity to instant SEQ ID NO:3
L180 to A/C/E/I/M/V
N
27
S182 to E/T/N/Q (2nd substitution)
L180 to A/C
N
28
L273 V/I/K
(3rd substitution)
Y
Graham/GenBank PAU49021 teaches L273V;
and has 71% identity to instant SEQ ID NO:3
29
L180 A/C
(4th substitution)
N
30
A202 L/V/F (5th substitution)
N
32
Y65 F/L/M (6th substitution)
N
33
C156 D/A/P/G/S (7th substitution)
N
34
T91P (8th substitution)
N
35
N231D (9th substitution)
N
36
Y244A or S245A or G267P
(10th substitution)
Y
Graham/GenBank PAU49021 teaches G267P;
and has 71% identity to instant SEQ ID NO:3
37
L197R (11th substitution)
N
38
Q60 V/K/R
(12th substitution)
N
39
D176 to L/V/K/R/Y (13th substitution)
N
Q11 to H/L/P/M/V/W
N
V12 to L/A/G/R
N
T13 to L/M/Q/A/G
N
A14 to M/R/G/P/L/T
N
K94 to R/V
N
A95 to I/C/V/L
N
A107 to S/G
N
H123 to N/Q/S
N
T126 to S/E
N
Q127 to G/T
N
L129 to C/K/V
N
M137 to G/A/D/H/N/S/T
N
D159L
N
A248V
N
T185 to V/L
N
Q190 to Q/A/P, and G122S
N
P191 to S/V/L/I/Y/K
N
Q192S
N
L195 to I/V
N
F212L
N
S268 to K/Q/H/R/L
N
A269 to L/G/R/W
N
T272A
N
40
SEQ ID NO:16
SEQ ID NO:31-100
Y
Graham/GenBank PAU49021 teaches Y200L and has 69.42% identity to instant SEQ ID NO:16
SEQ ID NO:4-15 and 20-30
N
Information Disclosure Statement
The information disclosure statement filed on 10/19/2023 complies with 37 CFR 1.98(a)(2), which requires a legible copy of each cited foreign patent document; each non-patent literature publication or that portion which caused it to be listed; and all other information or that portion which caused it to be listed. All references were considered.
Claim Objections
Claims 26, 27 and 40 are objected to because of the following informalities:
Claim 26 recites “SEQ ID No. 3” which recites a period after “No.” within the claim, and should be amended to replace the period with a colon as in “SEQ ID NO: 3”.
Claim 26 is missing a conjunction after the third wherein clause, and should be amended to include the word “and” before the last wherein clause.
Claim 27 is missing a conjunction between the two wherein clauses, and should be amended to include the word “and” after the first wherein clause.
Claim 40 recites “SEQ ID No. 15, SEQ ID No. 14, SEQ ID No. 13 …” which recites periods after each “No.” within the claim. It is suggested that the periods be changed to colons to recite “SEQ ID NO: 15, SEQ ID NO: 14, SEQ ID NO: 13 …”
Appropriate correction is required.
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.
Claims 26-40 are rejected under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor regards as the invention.
Claim 26 recites “a modified enzyme comprising a sequence SEQ ID NO:3 with a first substitution at a position selected from the group consisting of position 200, position 180, position 160 and position 236”. It is unclear if the sequence is required to comprise the full length of SEQ ID NO:3 except for at least one substitution at a position selected from position 200, 180, 160 or 236; or if the sequence can comprise more than one substitution at a position selected from position 200, 180, 160, or 236. It is further unclear whether the phrase “comprising a sequence SEQ ID NO:3” requires that the modified enzyme sequence has 100% sequence identity SEQ ID NO:3 except for the single required substitution, or whether the modified enzyme sequence only requires at least 3 consecutive amino acids that match in addition to the required substitution. It is further unclear whether “a first substitution” requires only one substitution at a position selected from the group consisting of position 200, 180, 160 or 236; or whether “first” is to be interpreted as “at least one” and a further substitution can occur at one or more additional positions selected from positions 200, 180, 160 or 236.
It is suggested that the phrasing “a first substitution” is amended to recite “a single substitution” or “a substitution” to obviate this rejection.
Claims 27-40 are rejected for depending from rejected claim 26 but failing to remedy the indefiniteness therein.
Claim 28 recites “the modified enzyme according to claim 26, further comprising a third substitution”. Claim 28 depends from claim 26, which requires a first substitution at a position selected from the group consisting of position 200, position 180, position 160, and position 236”. It is unclear what is meant by “third substitution” as there is no prior recitation of a “second substitution”. It is suggested that the word “third” be deleted to obviate this rejection.
Claim 29 recites “the modified enzyme according to claim 26, further comprising a fourth substitution at position 180, wherein the first substitution is not at position 180 and the second substitution if present is not at position 180”. Claim 29 depends from claim 26, which requires a first substitution at a position selected from the group consisting of position 200, position 180, position 160, and position 236”. It is unclear what is meant by “fourth substitution” as there is no prior recitation of a “second” or “third substitution”. Further, the phrase “the second substitution” lacks antecedent basis, as claim 26 does not recite “a second substitution”.
Claim 30 recites “the modified enzyme according to claim 26, further comprising a fifth substitution”. Claim 30 depends from claim 26, which requires a first substitution at a position selected from the group consisting of position 200, position 180, position 160, and position 236”. It is unclear what is meant by “fifth substitution” as there is no prior recitation of a “second”, “third”, or “fourth substitution”. It is suggested that the word “fifth” be deleted to obviate this rejection.
Claim 32 recites “the modified enzyme according to claim 26, further comprising a sixth substitution”. Claim 32 depends from claim 26, which requires a first substitution at a position selected from the group consisting of position 200, position 180, position 160, and position 236”. It is unclear what is meant by “sixth substitution” as there is no prior recitation of a “second”, “third”, “fourth” or “fifth substitution”. It is suggested that the word “sixth” be deleted to obviate this rejection.
Claim 33 recites “the modified enzyme according to claim 26, further comprising a seventh substitution”. Claim 33 depends from claim 26, which requires a first substitution at a position selected from the group consisting of position 200, position 180, position 160, and position 236”. It is unclear what is meant by “seventh substitution” as there is no prior recitation of a “second”, “third”, “fourth”, “fifth” or “sixth substitution”. It is suggested that the word “seventh” be deleted to obviate this rejection.
Claim 34 recites “the modified enzyme according to claim 26, further comprising an eighth substitution”. Claim 34 depends from claim 26, which requires a first substitution at a position selected from the group consisting of position 200, position 180, position 160, and position 236”. It is unclear what is meant by “eighth substitution” as there is no prior recitation of a “second”, “third”, “fourth”, “fifth”, “sixth” or “seventh substitution”. It is suggested that the word “eighth” be deleted to obviate this rejection.
Claim 35 recites “the modified enzyme according to claim 26, further comprising a ninth substitution”. Claim 35 depends from claim 26, which requires a first substitution at a position selected from the group consisting of position 200, position 180, position 160, and position 236”. It is unclear what is meant by “ninth substitution” as there is no prior recitation of a “second”, “third”, “fourth”, “fifth”, “sixth”, “seventh” or “eighth substitution”. It is suggested that the word “ninth” be deleted to obviate this rejection.
Claim 36 recites “the modified enzyme according to claim 26, further comprising a tenth substitution”. Claim 36 depends from claim 26, which requires a first substitution at a position selected from the group consisting of position 200, position 180, position 160, and position 236”. It is unclear what is meant by “tenth substitution” as there is no prior recitation of a “second”, “third”, “fourth”, “fifth”, “sixth”, “seventh”, “eighth” or “ninth substitution”. It is suggested that the word “tenth” be deleted to obviate this rejection.
Claim 37 recites “the modified enzyme according to claim 26, further comprising an eleventh substitution”. Claim 37 depends from claim 26, which requires a first substitution at a position selected from the group consisting of position 200, position 180, position 160, and position 236”. It is unclear what is meant by “eleventh substitution” as there is no prior recitation of a “second”, “third”, “fourth”, “fifth”, “sixth”, “seventh”, “eighth”, “ninth” or “tenth substitution”. It is suggested that the word “eleventh” be deleted to obviate this rejection.
Claim 38 recites “the modified enzyme according to claim 26, further comprising a twelfth substitution”. Claim 38 depends from claim 26, which requires a first substitution at a position selected from the group consisting of position 200, position 180, position 160, and position 236”. It is unclear what is meant by “twelfth substitution” as there is no prior recitation of a “second”, “third”, “fourth”, “fifth”, “sixth”, “seventh”, “eighth”, “ninth”, “tenth” or “eleventh substitution”. It is suggested that the word “twelfth” be deleted to obviate this rejection.
Claim 39 recites “the modified enzyme according to claim 26, further comprising a thirteenth substitution”. Claim 38 depends from claim 26, which requires a first substitution at a position selected from the group consisting of position 200, position 180, position 160, and position 236”. It is unclear what is meant by “thirteenth substitution” as there is no recitation of a “second”, “third”, “fourth”, “fifth”, “sixth”, “seventh”, “eighth”, “ninth”, “tenth”, “eleventh” or “twelfth substitution”. It is suggested that the word “thirteenth” be deleted to obviate this rejection.
Claim 40 recites “the modified enzyme according to claim 26, wherein the modified enzyme comprises a sequence selected from SEQ ID No. 15, SEQ ID No. 14, SEQ ID No. 13, SEQ ID No. 16, SEQ ID No. 12, SEQ ID No. 11, SEQ ID No. 10, SEQ ID No. 9, SEQ ID No. 8, SEQ ID No. 7, SEQ ID No. 6, SEQ ID No. 5, SEQ ID No. 4, and SEQ ID No. 20 to 100.” Claim 40 depends from Claim 26, which requires a modified enzyme comprising a sequence SEQ ID NO. 3 with a first substitution at a position selected from the group consisting of position 200, position 180, position 160, and position 236”. It is unclear whether claim 40 requires the modified enzyme to comprise an additional sequence selected from the listed alternatives, or SEQ ID NO:3 is encompassed by the alternative SEQ ID NOs listed in claim 40, making it unclear what amino acid sequence the enzyme is required to comprise.
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 26-40 are rejected under 35 U.S.C. 112(a) as failing to comply with the written description requirement. The claims 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, at the time the application was filed, had possession of the claimed invention.
Applicant is referred to MPEP 2163(II)(A)(3)(a)(i and ii), which states that 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 applicant was in possession of the claimed genus. 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. The disclosure of only one species encompassed within a genus adequately describes a claim directed to that genus only if the disclosure indicates that the patentee has invented species sufficient to constitute the genus. For inventions in an unpredictable art, adequate written description of a genus which embraces widely variant species cannot be achieved by disclosing only one species within the genus.
Claim 26 is drawn to a modified enzyme comprising a sequence SEQ ID NO:3 with a first substitution at a position selected from the group consisting of position 200, position 180, position 160 and position 236. Claims 27-39 are drawn to the modified enzyme of claim 26, further comprising one additional substitution at a specific amino acid position selected from a group of particular amino acids. Claim 40 is drawn to the modified enzyme of claim 26, comprising a sequence selected from SEQ ID NO:4-16 or SEQ ID NO: 20-100. The specification does not disclose a representative number of modified enzymes having the recited substitutions that correspond to the genus of possible enzyme activities.
The current specification describes a modified enzyme comprising a first substitution of base SEQ ID NO:3 at a position selected from the group consisting of position 200, position 180, position 160 and position 236 (p.2, [0004]). The current specification further describes a modified enzyme comprising a second, third, fourth, fifth, sixth, seventh, eighth, ninth, tenth, eleventh, twelfth and thirteenth substitution at specific positions relative to SEQ ID NO:3 (p.2-4, [0005] – [0016]). The specification further describes a modified enzyme comprising a sequence selected from the group consisting of SEQ ID NO:4-16 or SEQ ID NO:20-100 [p.4, [0017]). The specification provides specific examples of selected methyltransferases (pMT1, SaMT, and ScMT) (Fig. 2a). The specification further describes structure-based enzyme engineering to improve pMT activity, by creating mutant libraries starting with Gly85 mutants [0079]-[0082], Y200 mutagenesis [0083], and site-saturation mutagenesis on L180 and S182 [0084].
The specification does not provide any guidance on the structure-function relationship of SEQ ID NO:3; does not provide any information on what type of enzymatic function or activity the modified enzymes should or should not have; and does not provide any guidance on whether a specific percent sequence identity is required to SEQ ID NO:3 other than the required substitutions. Based on the lack of an art-recognized structure-function relationship of the genus of modified enzymes and enzyme activities, it is highly unpredictable as to what modified enzyme sequences would correspond to the genus of enzyme activities encompassed by modified enzymes comprising any sequence identity to SEQ ID NO:3.
Graham et al. (“Genome sequence of Streptomyces albireticuli NRRL B-1670”, GenBank accession number PAU49021, deposited on September 5, 2017, Direct Submission) discloses a methyltransferase type 11 comprising a leucine at position 200 relative to instant SEQ ID NO:3; a valine in position 273 relative to instant SEQ ID NO:3; and a proline in position 267 relative to instant SEQ ID NO:3. The sequence taught by Graham has 71% identity to the amino acid sequence of SEQ ID NO:3, and 69% identity to instant SEQ ID NO:16. Graham does not disclose the activity of the methyltransferase 11 relative to wildtype, nor provide any guidance on what amino acid positions guide the structure-function relationship of the methyltransferase enzyme.
The disclosure of a single species of a modified methyltransferase enzyme having an amino acid sequence according to SEQ ID NO:3 with amino acid substitutions in 13 positions is not considered to constitute a representative number of species of the genus of enzyme activities, in view of the lack of any guidance as to what % identity to the full length of SEQ ID NO:3 is required of the modified enzyme. Thus, one of ordinary skill in the art could not conclude that Applicant was in possession of the claimed genus of modified enzymes comprising any percent identity to SEQ ID NO:3 and having a substitution at the positions required by the claims. This disclosure does not constitute a representative number of species of the genus in view of the potential breadth and variability of the genus, and so there is a failure to satisfy the written description requirement for the genus.
Claim Rejections - 35 USC § 102
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.
Claims 26, 28, 36 and 40 are rejected under 35 U.S.C. 102(a)(1) as being clearly anticipated by Graham et al. (“Genome sequence of Streptomyces albireticuli NRRL B-1670”, GenBank accession number PAU49021, deposited on September 5, 2017, Direct Submission).
As the claims do not require a particular percent identity to SEQ ID NO:3, the claims are being interpreted to include any type of enzyme with any percentage identity to instant SEQ ID NO:3. Therefore, the following claims are anticipated by Graham et al. (“Genome sequence of Streptomyces albireticuli NRRL B-1670”, GenBank accession number PAU49021, deposited on September 5, 2017, Direct Submission).
Regarding claim 26, Graham teaches a methyltransferase type 11 comprising a leucine in position 200 relative to instant SEQ ID NO:3.
Regarding claim 28, Graham teaches a methyltransferase type 11 further comprising a valine in position 273 relative to instant SEQ ID NO:3.
Regarding claim 36, Graham teaches a methyltransferase type 11 further comprising a proline in position 267 relative to instant SEQ ID NO:3.
Regarding claim 40, Graham teaches a methyltransferase type 11 comprising an amino acid sequence that has 69% identity to instant SEQ ID NO:16, and comprises a leucine in position 200 relative to instant SEQ ID NO:3.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to DEEPA MISHRA whose telephone number is (571) 272-6464. The examiner can normally be reached Monday - Friday 9:30am - 3:30pm EST.
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/DEEPA MISHRA/Examiner, Art Unit 1657
/LOUISE W HUMPHREY/Supervisory Patent Examiner, Art Unit 1657
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