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
Pursuant to a preliminary amendment filed June 15, 2022, claims 1-11 are currently pending in the instant application.
Response to Election/Restriction
Applicant's election with traverse of Group I, claims 1-6, directed to a method for analyzing a target nucleic acid; and Applicant’s election of Species without traverse as follows:
Species (A): further comprising determining a property dependent on the target nucleic acid other than its sequence (claim 3); and
Species (B): wherein the nucleotides of the mutation sites of one, two, or more libraries (claim 6), in the reply filed December 10, 2025 is acknowledged.
Response to Traversals:
The traversal of is on the grounds that: (a) claim 7 should be examined with Group I (claims 1-6) because claim 7 requires analyzing the libraries by a method according to claim 1, such that claim 7 includes all of the limitations of claim 1 (Applicant Remarks, pg. 1, second full paragraph)
Regarding (a), as indicated in the Requirement for Restriction/Election mailed October 10, 2025, Groups I-V lack unity of invention because even though the inventions of these groups require the technical feature of an analyzer, it does not make a contribution over the prior art in view of Short (US20110165627). Applicant does not provide any arguments regarding the technical feature, Groups I-V, and/or their lack of unity of invention in view of Short. Moreover, it is noted that each of Groups III-V do not recite all of the limitations of Group I. Thus, the restriction is proper.
Claims 7-11 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a non-elected invention, there being no allowable generic or linking claim. Applicant timely
traversed the restriction (election) requirement in the reply filed on December 10, 2025.
Claims 2 and 5 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a non-elected species, there being no allowable generic or linking claim.
The restriction requirement is still deemed proper and is therefore made FINAL.
The claims will be examined insofar as they read on the elected species.
Therefore, claims 1, 3, 4 and 6 are under consideration to which the following grounds of rejection are applicable.
Priority
The present application filed June 15, 2022, is a 35 U.S.C. 371 national stage filing of
International Application No. PCT/EP2020/086800, filed December 17, 2020, which claims the benefit of European Patent Application EP19217297.1, filed December 18, 2019.
Acknowledgment is made of applicant's claim for foreign priority based on an application filed in Germany on March 26, 2020 including the certified copy of the German Patent Application 10-2020-108-373.4 as required by 37 CFR 1.55.
Information Disclosure Statement
The information disclosure statements (IDSs) submitted on June 15, 2022; September 1, 2022 and December 10, 2025 have been considered. Initialed copies of the IDSs accompany this Office Action.
Claim Objections/Rejections
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.
Claims 1, 3, 4 and 6 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 applicant regards as the invention.
Claim 1 is indefinite for the recitation of the terms “the members;” “each member;” “one member;” and “respective member,” such as recited in claim 1, lines 3, 6, 7 and 9. There is insufficient antecedent basis for the terms “the members;” “each member;” “one member;” and “respective member” in the claim because claim 1, line 2 recites the term “isolated members.”
Claims 1 and 6 are indefinite for the recitation of the terms “the mutation sites” and “the respective mutation sites” such as recited in claim 1, lines 4 and 8. There is insufficient antecedent basis for the term “the mutation sites” and “the respective mutation sites” in the claim because claim 1, line 4 recites the term “one or more library-specific mutation sites.”
Claim 1 is indefinite for the recitation of the term “the respectively mutated target nucleic acid sites” such as recited in claim 1, lines 7-8. There is insufficient antecedent basis for the term “the respectively mutated target nucleic acid sites” in the claim because claim 1, lines 4-5 recites the term “a target nucleic acid mutated at one or more library-specific mutation sites.”
Claims 1 and 6 are indefinite for the recitation of the term “the nucleotides” such as recited in claim 1, line 8. There is insufficient antecedent basis for the term “the nucleotides” in the claim.
Claim 1 is indefinite for the recitation of the term “the respective mutation sites” such as recited in claim 1, line 8. There is insufficient antecedent basis for the term “the respective mutation sites” in the claim because claim 1, line 4 recites the term “one or more library-specific mutation sites.”
Claim 3 is indefinite for the recitation of the term “at least one member” such as recited in claim 3, lines 1-2. There is insufficient antecedent basis for the term “at least one member” in the claim because claim 1, line 2 recites the term “isolated members.”
Claim 3 is indefinite for the recitation of the term “step ii)” such as recited in claim 3, line 2. There is insufficient antecedent basis for the term “step ii)” in the claim because claim 1, line 6 recites the term “ii).”
Claim 3 is indefinite for the recitation of the term “a property dependent on the target nucleic acid other than its sequence is determined” such as recited in claim 3, lines 2-3 because claim 3 depends from instant claim 1, wherein claim 1 does not recite a property of the target nucleic acid, determining a property of the target nucleic acid and/or sequencing the target nucleic acid. Instead, claim 1 recite sequencing the probe nucleic acids of the mixture and, thus, the metes and bounds of the claim cannot be determined.
Claim 4 is indefinite for the recitation of the term “a protein encoded by the target nucleic acid” such as recited in claim 4, line 2 because claim 4 depends from instant claims 1 and 3, wherein claims 1 and 3 do not recite the presence of a protein encoded by the target nucleic acid and, thus, the metes and bounds of the claim cannot be determined.
Claim 6 is indefinite for the recitation of the term “one, two or more libraries” such as recited in claim 6, line 2. There is insufficient antecedent basis for the term “one, two or more libraries” in the claim because claim 1, line 2 recites the term “a set of two or more mutagenesis libraries.”
Claim 6 is indefinite for the recitation of the term “the target nucleic acid sequence” such as recited in claim 6, lines 3 and 5. There is insufficient antecedent basis for the term “the target nucleic acid sequence” in the claim.
Claim 6 is indefinite for the recitation of the terms “one or more arbitrary nucleotides;” “one or more degenerate nucleotides;” and a “predefined set of nucleotide or nucleotide sequences” such as recited in claim 6, lines 3-8. There is insufficient antecedent basis for the term “one or more arbitrary nucleotides” in the claim. Moreover, claim 6 depends from claim 1, wherein claim 1 does not recite the presence of ‘one or more arbitrary nucleotides;’ ‘one or more degenerate nucleotides;’ and ‘predefined set of nucleotide or nucleotide sequences’ and, thus, the metes and bounds of the claim cannot be determined.
Claim 6 is indefinite for the recitation of the terms “predefined set of nucleotide or nucleotide sequences” such as recited in claim 6, line 8 because the meaning of and/or difference between a “predefined set of nucleotide” and “nucleotide sequences” is unclear and, thus, the metes and bounds of the claim cannot be determined.
Claim Rejections - 35 USC § 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.
Claims 3, 4 and 6 are rejected under 35 U.S.C. 112(d) 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 3 recites (in part): “wherein for at least one member selected in step ii) a property dependent on the target nucleic acid other than its sequence is determined” in lines 1-3 because claim 3 depends from instant claim 1, wherein claim 1 does not recite a step ii), determining a property dependent on the target nucleic acid, sequencing the target nucleic acid, etc. Thus, claim 3 is an improper dependent claim 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 4 recites (in part): “wherein the a …cell wall, excretion” in lines 1-15 because claim 4 depends from instant claims 1 and 3, wherein claims 1 and 3 do not recite a protein encoded by the target nucleic acid. Thus, claim 4 is an improper dependent claim 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 6 recites (in part): “wherein the nucleotides of the mutation sites of one, two or more libraries…a predefined set of nucleotide or nucleotide sequences” in lines 2-8 because claim 6 depends from claim 1, wherein claim 1 does not recite one, two or more libraries, arbitrary nucleotides, degenerate nucleotides, a predefined set of nucleotide or nucleotide sequences. Thus, claim 6 is an improper dependent claim 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.
Applicant may cancel the claim, amend the claim to place the claim in proper dependent form, rewrite the claim in independent form, or present a sufficient showing that the dependent claim complies with the statutory requirements.
Claim Rejections - 35 USC § 102
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 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 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 1, 3, 4 and 6 are rejected under 35 U.S.C. 102(a1)/102(a2) as being anticipated by Cozens et al. (hereinafter “Cozens”) (Nucleic Acids Research, 2018, 46(8), 1-13).
Regarding claim 1, Cozens teaches a new library assembly method to uncompromisingly address all four quality bottlenecks of simultaneous multiple site saturation mutagenesis, wherein Darwin Assembly is a simple, fast, low-cost and flexible platform capable of delivering large (>108 transformations), user-defined libraries with any desired combinations of mutations anywhere in a gene of interest, or in multiple genes/features in a plasmid, which takes a single working day and is both highly effective and efficient (all clones mutated at all positions targeted) (pg. 2, col 1, first full paragraph). Cozens teaches that scanning libraries introduce a single point mutation at different sites in a target gene, where alanine scanning is a traditional approach to identify functionally important residues in enzymes but scanning libraries can also be used to map the local functional neighborhood of an enzyme or even to generate datasets for deep mutational scanning-guided rational protein design, wherein mutant generation can be laborious when mutations are introduced individually by site-directed mutagenesis (interpreted as site mutagenesis; interpreting scanning libraries as a set of two or more libraries; and providing isolated library members, claim 1(i) (pg. 8, col 1, second full paragraph). Cozens teaches that Darwin Assembly can efficiently generate scanning libraries by combining oligonucleotides targeting the same binding site, but each introducing a different mutation, such that using the CAT gene as the model, an alanine scan library was assembled around residues Thr101 and Ser104, using Leu105 (CTC→CTG) recording as an assembly control, such that five inner oligonucleotides were designed: four introducing an alanine mutation (Thr101Ala, Phe102Ala, Ser103Ala, or Ser104Ala) and one wild-type, such that all five oligonucleotides introduced the CTC→CTG control mutation at the Leu105 codon (interpreted as selecting one member of each site mutagenesis library; and obtaining a probe nucleic acid of the target mutated nucleic acid, claim 1(ii) and 1(iii)) (pg. 8, col 1, third full paragraph). Cozens teaches that the five oligonucleotides were mixed in a 1:1:1:1:1 ratio in the assembly reaction to create a library where each variant was expected to be 20% of the final population, wherein assembly was successful and over 103 transformants were isolated, pooled, their plasmid DNA purified and deep sequenced––generating nearly 80,000 reads, such that the control Leu105 (CTC→CTG) mutation was present in 99.7% of the samples, a frequency comparable to sites that had not been targeted for mutagenesis (see Table 2) (interpreted as mixing probe nucleic acids; and sequencing the probe nucleic acids of the mixture obtained in step iv in parallel, claim 1(iv) and 1(v)) (pg. 8, col 1, fourth full paragraph). Cozens teaches Illumina sequencing and data analysis, wherein deep sequencing was carried out on an Illumina MiSeq at the UCL Genomics Center using an 150 cycle MiSeq Reagent Kit v3 (interpreted as sequencing in parallel, claim 1(v)) (pg. 6, col 2, second full paragraph).
Regarding claims 3 and 4, Cozens teaches that natural enzymes are optimized to their in vivo setting and are often unsuited for the synthesis of biological or synthetic compounds in vitro, such that expression and functional optimization, or more radical engineering is often required to generate the desired enzymatic activity, whether boosting an existing activity or changing enzyme function altogether, where those needs have led to the flourishing of directed evolution and protein engineering and it has repeatedly proven possible to enhance a number of protein properties, including expression, folding, thermostability, substrate specificity and catalytic efficiency (interpreted as a property of the target nucleic acid selected from expression, activity, etc., claims 3 and 4) (pg. 1, col 1, first partial paragraph; and col 2, first partial paragraph).
Regarding claim 6, Cozens teaches that Darwin Assembly can efficiently generate scanning libraries by combining oligonucleotides targeting the same binding site, but each introducing a different mutation, such that using the CAT gene as the model, an alanine scan library was assembled around residues Thr101 and Ser104, using Leu 105 (CTC→CTG) recording as an assembly control, such that five inner oligonucleotides were designed: four introducing an alanine mutation (Thr101Ala, Phe102Ala, Ser103Ala, or Ser104Ala) and one wild-type, such that all five oligonucleotides introduced the CTC→CTG control mutation at the Leu105 codon (interpreted as differ from the target nucleic acid sequence by one or more arbitrary nucleotides; and are selected from a predefined set of nucleotide sequences, claim 6) (pg. 8, col 1, third full paragraph).
Cozens meets all the limitations of the claims and, therefore, anticipates the claimed invention.
Conclusion
Claims 1, 3, 4 and 6 are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to AMY M BUNKER whose telephone number is (313) 446-4833. The examiner can normally be reached on Monday-Friday (6am-2:30pm).
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/AMY M BUNKER/Primary Examiner, Art Unit 1684