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 .
Application Status
This action is written in response to applicant’s correspondence received 02/26/2024. Claims 1-20 are currently pending and are examined herein.
Claim Interpretation
“During examination, statements in the preamble reciting the purpose or intended use of the claimed invention must be evaluated to determine whether or not 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.” (MPEP 2111.02). Further, “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.” (Id.). Further, “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” (Id.).
In the instant case, claims 1-5, 9 and 11-12 are drawn to a composition, and the body of the claims fully sets forth a structurally complete composition, which is a base editing system comprising a Cas9 nuclease, TadA deaminase, and 3-methyladenine glycosylase. Therefore, for the purposes of comparison to the prior art, the intended use of the system for achieving A-to-C and/or A-to-T base mutations is not considered a limitation. Similarly, claims 6, 10, and 13-20 are drawn to a method for achieving A-to-C and/or A-to-T base mutations. This is a statement of purpose, and does not result in a manipulative difference in the method, i.e., a difference in the method steps. In the case of claims 7 and 8, however, the method comprises a step of achieving the recited base mutations, and a mechanism of action to achieve them. Those limitations are considered limiting because they are positive steps that result in a manipulative difference.
It is also relevant to note that claim 1 recites “a base editing system”. The broadest reasonable interpretation of “system” comprises systems and compositions comprising each of those elements as individual protein, as well as systems and compositions comprising two or more of those elements as fusion proteins.
Regarding claim 5:
Claim 5 recites, “the Cas9 nuclease is further configured to be replaced with nucleases capable of specifically recognizing DNA and having a cutting function”. This is interpreted as a product produced by a process of configuring the Cas9. This is also interpreted as a removal of the Cas9 nuclease and replacement with any nuclease with the required function.
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 1-20 are 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 1 is unclear over recitation of, “a base editing system…comprising adenosine deaminase TadA, Cas9 nuclease, 3-methyladenine DNA glycosylase, and variants of the 3-methyladenine DNA glycosylase”. This language is considered to be indefinite because the claim recites both the glycosylase and variants thereof as components of the system, and it is unclear from the phrasing whether the system requires either a 3-methyladenine DNA glycosylase or a variant, or whether the system requires both components to be present. In FIG. 2, the specification discloses systems comprising a TadA, Cas9 nuclease, and a single DNA glycosylase. From that, it is inferred that the claim is not reciting a list of alternatives, but is instead reciting a list of required components. However, the specification does not actually disclose any systems with two types of glycosylase, as the claim’s language suggests. Therefore, the metes and bounds of the claimed system are unclear.
Amending the claim to “A base editing system for achieving A-to-C and/or A-to-T base mutations, comprising adenosine deaminase TadA; Cas9 nuclease; and 3-methyladenine DNA glycosylase or variants thereof.” would obviate this rejection.
Claim 5 has similar phrasing, in which a series of Cas9 nucleases is listed and it is not clear whether the list is meant to be in the alternative or and is indefinite by the same rationale. It is also unclear whether “the Cas9 nickase is derived from Streptococcus pyogenes” is intended to be an alternative embodiment of the nickase, or is intended to limit the earlier recited nickase.
Those claims identified in the statement of rejection but not explicitly referenced in the rejection are also rejected for depending from a rejected claim but failing to remedy the indefiniteness therein.
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 5, 11-12, 18, 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.
As discussed in Claim Interpretation above, claim 5 states that the Cas9 nuclease is configured to be replaced. In other words, claim 5 effectively recites a method step in which the Cas9 nuclease required by the system of claim 1 is omitted and replaced with another, generic nuclease. MPEP 608.01(n).G.III states, “ the test as to whether a claim is a proper dependent claim is that it shall include every limitation of the claim from which it depends and specify a further limitation of the subject matter claimed. For example, if claim 1 recites the combination of elements A, B, C, and D, a claim reciting the structure of claim 1 in which D was omitted or replaced by E would not be a proper dependent claim, even though it placed further limitations on the remaining elements or added still other elements”. In the instant case, claim 1 recites the combination of elements A (TadA), B (Cas9 nuclease), and C (the glycosylase), while claim 5 omits element B and replaces it with element D (a generic DNA-specific cutting nuclease). Per MPEP 608.01(n).G.III, this renders claim 5 an improper dependent claim under 35 U.S.C. 112(d) because it does not include all the limitations of the claim from which it depends.
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.
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.
Claim 1 is rejected under 35 U.S.C. 101 because the claimed invention is directed to a product of nature without significantly more.
Claim 1 is drawn to a base editing system comprising adenosine deaminase TadA, Cas9 nuclease, and 3-methyladenine DNA glycosylase. Please see Claim Interpretation above for the broadest reasonable interpretation of the claim. In brief, the intended use of the system is not considered a limitation, and a base editing system includes composition comprising each protein individually.
Subject Matter Eligibility Analysis
Eligibility Step 1 (MPEP 2106.03): Is the claim drawn to a statutory category.
The claim is to a composition of matter, and is eligible at Step 1.
Eligibility Step 2A Prong One (MPEP 2106.04(II)(A)(1)): Is the claim directed to a judicial exception?
The claim is directed to a system (i.e., a composition comprising) an adenosine deaminase TadA, Cas9 nuclease, and 3-methyladenine DNA glycosylase. This is a judicial exception because it reads on at least a Streptococcus aureus cell comprising the recited proteins in its cytoplasm. A S. aureus cell is a composition of matter. As evidenced by Yourik, S. aureus comprises a Cas9 nuclease (Yourik et al. Staphylococcus aureus Cas9 is a multiple-turnover enzyme. RNA. 2019 Jan;25(1):35–44.). As evidenced by Zhu, S. aureus comprises a 3-methyl-adenine DNA glycosylase I (TAG) protein (Zhu et al. A model for 3-methyladenine recognition by 3-methyladenine DNA glycosylase I (TAG) from Staphylococcus aureus. Acta Cryst. (2012). F68, 610–615.). As evidenced by Losey, S. aureus comprises a tRNA adenosine deaminase TadA (Losey et al. Crystal structure of Staphylococcus aureus tRNA adenosine deaminase TadA in complex with RNA. Nat Struct Mol Biol 13, 153–159 (2006).).
Eligibility Step 2A Prong One: Markedly Different Characteristics (MPEP 2106.04(c)):
“The markedly different characteristics analysis compares the nature-based product limitation to its naturally occurring counterpart in its natural state. Markedly different characteristics can be expressed as the product’s structure, function, and/or other properties, and are evaluated based on what is recited in the claim on a case-by-case basis. If the analysis indicates that a nature-based product limitation does not exhibit markedly different characteristics, then that limitation is a product of nature exception.” (MPEP 2106.04(c)). In the instant case, the closest naturally occurring counterpart to the claimed product is a S. aureus cell, as described in Step 2A Prong One above. Claim 1 recites no additional elements which render the claimed composition markedly different from its closest naturally occurring counterpart.
Eligibility Step 2A Prong Two (MPEP 2106.04(d)): Does the claim integrate the exception into a practical application?
Claim 1 does not recite additional elements beyond the system itself. The recitation of the variants of the 3-methyladenine DNA glycosylase is interpreted as an alternative embodiment.
Eligibility Step 2B (MPEP 2106.05): The claim does not include additional
elements that are sufficient to amount to significantly more than the judicial exception.
Claim 5 is included in this rejection because the TadA being derived from S. aureus does not render the claimed system markedly different from a naturally occurring S. aureus cell comprising a native TadA. While the limitation of the Cas9 nuclease being configured to be replaced is considered indefinite, as described above, the broadest reasonable interpretation of “configured to be replaced” includes Cas9 nuclease coding sequences which include naturally occurring structures which would facilitate its removal from the genome, such as nucleotide sequences which function as restriction endonuclease recognition sites, CRISPR PAM recognition sites, etc.
Claims 2-4 are excluded from this rejection because they recite specific sequences or a TadA derived from rats, mice or B. subtilis. A search of the art did not reveal that B. subtilis comprises a native Cas9 nuclease, nor do mammals such as rats and mice comprise a Cas9 nuclease or a TadA adenine deaminase.
Claims 11-12 are excluded from this rejection because they limit the TadA to one derived from E. coli. A naturally occurring S. aureus cell would not be expected to comprise an E. coli TadA. One which did comprise an E. coli TadA would be markedly different from its naturally occurring counterpart.
Claim Rejections - 35 USC § 112(a) - Enablement
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.
Claim 5 is rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
Claim 5 recites, “the Cas9 nuclease is further configured to be replaced with nucleases capable of specifically recognizing DNA and having a cutting function”. This phrase is not considered a, “means or step plus function” limitation invoking 35 U.S.C. 112(f) because the term “Cas9 nuclease” has a specific structural meaning and is not considered a generic placeholder or nonce term, and thus the phrase does not pass step A of the 3-prong analysis (MPEP 2181.I). However, the claim is considered indefinite because it is not clear how the Cas9 is to be configured to be replaced with nucleases capable of specifically recognizing DNA and having a cutting function. The specification does not provide any guidance or examples of configuring a Cas9 nuclease to be replaced with another nuclease capable of specifically recognizing DNA and having a cutting function, and it is unclear what structural changes to the Cas9 nuclease the ordinary artisan would be required to implement to configure the nuclease to achieve the stated functional outcome.
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.
(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, 3-8, 11, 13, and 16-18 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by U.S. PGPUB No. 2021/0403898 A1 to Kim (published 12/20/2021, effective filing date 06/30/2020, hereinafter ‘Kim’).
Regarding claim 1:
Kim teaches a base editing system for achieving A-to-C and/or A-to-T base mutations, comprising adenosine deaminase TadA, Cas9 nuclease, and 3-methyladenine DNA glycosylase:
[0237] Several glycosylase domains were fused to either the N-terminus or C-terminus of ABE8.20m (SEQ ID NO:57)…Three putative inosine glycosylases were tested, which are…mMPG from Mus musculus (SEQ ID NO:83, UniProtKB—Q04841)
[0239] FIG. 9 shows the editing efficiency of target adenines in the base editing window to cytosine and thymine bases for each of the four sites and different architectures.
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839
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As evidenced by UniProt Q04841, mMPG is inherently a DNA-3-methyladenine glycosylase (see attached).
As evidenced by Gaudelli, ABE8.20 is a term known in the art which inherently refers to an adenine base editor (ABE) construct comprising a TadA deaminase and catalytically impaired Cas9 (Gaudelli et al. Directed evolution of adenine base editors with increased activity and therapeutic application. Nat Biotechnol. 2020 Jul;38(7):892-900.):
ABE is a molecular machine comprising an evolved Escherichia coli tRNAARG-modify
ing enzyme, TadA, covalently fused to a catalytically impaired Cas9 protein (D10A nickase Cas9, nCas9) (Fig. 1a,b). (p. 892)
we selected a subset of ABE8 constructs…ABE8.20-m (p. 893)
Fig. 1… TadA* deaminase chemically converts adenine to inosine
In summary, Kim teaches base editing systems such as ABE8.20m-hMPG, and while Kim does not explicitly state that the system comprises a dCas9, TadA, and DNA 3-methyladenine glycosylase, they describe working examples of systems (e.g., ABE8.20-mMPG) using art-recognized terms for the recited components.
Regarding claims 3 and 4, Kim teaches that ABE8.20-mMPG, which is derived from mice, comprises SEQ ID NO: 83, which comprises an amino acid sequence with 100% identity to instant SEQ ID NO: 7, as shown below:
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710
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Regarding claim 5, Kim as evidenced by Gaudelli teaches that the source of the TadA is E. coli (see above) and the Cas9 enzyme is a dCas9 nickase (also see above).
Regarding claims 6-7, 13, and 16-18, Kim teaches that the ABE8.20m-glycosylase fusion constructs were expressed in human/eukaryotic/mammalian host cells:
[0238] The following plasmids were transfected into HEK293T cells: a plasmid encoding ABE8.20m or a fusion protein including ABE8.20m fused to one of the above inosine glycosylases, and a plasmid encoding a guide RNA.
Regarding claim 8, the targeting of a sequence by a dCas9/guide RNA complex, the deamination of adenine to hypoxanthine by TadA, and excision of hypoxanthine by 3-methyladenine DNA glycosylase, and the base conversions under the mediation of endogenous DNA damage repair, and the editing window range is A2-A10, are all merely inherent functions which flow from those structures, as evidenced by the following art:
Kamat states, “Adenine deaminase…catalyzes the conversion of adenine to hypoxanthine. (Kamat et al. Catalytic Mechanism and Three-Dimensional Structure of Adenine Deaminase. Biochemistry 2011, 50, 1917–1927.)
Wyatt, in Table 1, shows that mouse 3-methyladenine DNA glycosylase excises hypoxanthine, and states that, “DNA glycosylases cleave theN-glycosylic bond between the target base and the deoxyriboseto produce an abasic site” (Wyatt et al. 3-methyladenine DNA glycosylases: structure, function, and biological importance. (1999) BioEssays 21:668–67.)
Gaudelli shows the ABE8 editing window in Figure 1e, which is ~A2-A10.
Regarding claim 11, Kim teaches wherein the TadA is derived from E. coli, as already described above.
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.
Claim 12 is rejected under 35 U.S.C. 103 as being unpatentable over U.S. PGPUB No. 2021/0403898 to Kim (cited above), as applied to claims 1, 3-8, 11, 13, and 16-18, in view of Richter (Richter et al. Phage-assisted evolution of an adenine base editor with improved Cas domain compatibility and activity. Nature Biotechnology volume 38, pages883–891 (2020)).
Kim teaches the base editing system of claims 1, 5 and 11, from which the instantly rejected claims depend, as described above.
Kim does not teach wherein the TadA is TadA-8e.
Richter teaches TadA-8e, which has an additional mutation in the TadA-8e domain which can ameliorate, “Cas9-dependent and -independent DNA off-target editing, and in transcriptome-wide RNA off-target editing” (Abstract).
It would have been prima facie obvious to a person having ordinary skill in the art before the effective filing date of the claimed invention to have modified the ABE8.20-mMPG base editing system, as taught by Kim, by incorporating the TadA-8e deaminase, as taught by Richter. The ordinary artisan would have been motivated to do so, and would have had a reasonable expectation of success, by Richter’s teachings that the TadA-8e enzyme reduced off-target editing.
Claims 9-10 and 14 are rejected under 35 U.S.C. 103 as being unpatentable over U.S. PGPUB No. 2021/0403898 to Kim (cited above), as applied to claims 1, 3-8, 11, 13, and 16-18, in view of Gaudelli (cited above) and Ahern (The Scientist, Vol:9, #15, pg 20, July 24, 1995).
Kim teaches the system of claim 1, from which the instantly rejected claims depend.
Kim does not a product comprising the base editing system of claim 1, wherein the product comprises a kit and pharmaceutical composition.
Gaudelli teaches that ABE systems have been used in vivo, i.e., in pharmaceutical compositions (p. 892).
Ahern teaches that, “More researchers are buying premade reagents and kits because they are convenient and they save time…Rather than browsing through catalogs and buying individual chemicals from one or several suppliers, investigators can instead purchase a kit that supplies all of the necessary reagents for a particular research application and even provides them with detailed instructions to follow.” (p. 5/8).
It would have been prima facie obvious to a person having ordinary skill in the art before the effective filing date of the claimed invention to have included the base editing system as taught by Kim in a pharmaceutical composition and kit, as taught by Gaudelli and Ahern, to yield a convenient, time-saving product ready for pharmaceutical applications.
Subject Matter Free of the Prior Art
The prior art does not teach or suggest 3-methyladenine DNA glycosylases comprising SEQ ID NOs: 2-4 in their entirety, with 100% identity, as claim 2 is interpreted as requiring.
The closest prior art to SEQ ID NO: 2 is the Mus musculus 3-methylpurine DNA glycosylase mRNA sequence, which however only has 55.8% overall identity to SEQ ID NO: 2:
MMU10420
LOCUS MMU10420 1061 bp mRNA linear ROD 01-JUL-1994
DEFINITION Mus musculus 3T3L1 methyl purine glycosylase (Mpg) mRNA, complete
cds.
ACCESSION U10420 S55313
VERSION U10420.1
KEYWORDS .
SOURCE Mus musculus (house mouse)
ORGANISM Mus musculus
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha;
Muroidea; Muridae; Murinae; Mus; Mus.
REFERENCE 1 (bases 1 to 1061)
AUTHORS Engelward,B.P., Boosalis,M.S., Chen,B.J., Deng,Z., Siciliano,M.J.
and Samson,L.D.
TITLE Cloning and characterization of a mouse
3-methyladenine/7-methyl-guanine/3-methylguanine DNA glycosylase
cDNA whose gene maps to chromosome 11
JOURNAL Carcinogenesis 14 (2), 175-181 (1993)
PUBMED 8435858
REFERENCE 3 (bases 1 to 1061)
AUTHORS Engelward,B.P.
TITLE Direct Submission
JOURNAL Submitted (07-JUN-1994) Bevin P. Engelward, Molecular and Cellular
Toxicology, Harvard School of Public Health, 665 Huntington Avenue,
Boston, MA 02115
COMMENT On Jun 21, 1994 this sequence version replaced gi:265938.
FEATURES Location/Qualifiers
source 1..1061
/organism="Mus musculus"
/mol_type="mRNA"
/strain="3T3L1"
/db_xref="taxon:10090"
/chromosome="11"
/clone="pBE1.1"
gene 1..1061
/gene="Mpg"
CDS 30..1031
/gene="Mpg"
/function="recognizes damaged bases and releases them by
cutting the glycosylic bond"
/note="also known as alkyl-adenine glycosylase (Aag), or
3-methyladenine DNA glycosylase"
/codon_start=1
/product="methyl purine glycosylase"
/protein_id="AAA19487.1"
/translation="MPARGGSARPGRGSLKPVSVTLLPDTEQPPFLGRARRPGNARAG
SLVTGYHEVGQMPAPLSRKIGQKKQRLADSEQQQTPKERLLSTPGLRRSIYFSSPEDH
SGRLGPEFFDQPAVTLARAFLGQVLVRRLADGTELRGRIVETEAYLGPEDEAAHSRGG
RQTPRNRGMFMKPGTLYVYLIYGMYFCLNVSSQGAGACVLLRALEPLEGLETMRQLRN
SLRKSTVGRSLKDRELCSGPSKLCQALAIDKSFDQRDLAQDDAVWLEHGPLESSSPAV
VVAAARIGIGHAGEWTQKPLRFYVQGSPWVSVVDRVAEQMDQPQQTACSEGLLIVQK"
regulatory 1003
/regulatory_class="polyA_signal_sequence"
/gene="Mpg"
ORIGIN
Query Match 55.8%; Score 548.8; Length 1061;
Best Local Similarity 74.4%;
Matches 720; Conservative 0; Mismatches 242; Indels 6; Gaps 2;
Qy 7 CGTGGCGGCACGGCAAGACTGGGCAGAGGAAGCCTGAAGCCCGTAAGCGTAGTCCTG--- 63
|| || || | || | | |||||||||| ||| || || || ||| ||||
Db 39 CGCGGTGGTAGTGCGCGCCCGGGCAGAGGATCCCTAAAACCGGTGTCCGTGACCCTGCTC 98
Qy 64 CCCGACACCGAGCACCCCGCCTTCCCCGGCAGAACACGAAGACCCGGAAATGCCAGAGCC 123
|||||||||||||| || | || | || || | || | || || |||||||||||
Db 99 CCCGACACCGAGCAGCCTCCATTTCTTGGACGAGCCCGCCGCCCAGGGAATGCCAGAGCA 158
Qy 124 GGCAGCCAAGTGACCGGCTCTAGAGAGGTGGGCCAGATGCCCGCCCCCCTGAGCAGAAAG 183
|| || ||||||||| | | ||||| ||||||||||| || || || | |||||
Db 159 GGATCCCTAGTGACCGGATATCATGAGGTCGGCCAGATGCCAGCGCCGCTTTCCCGAAAG 218
Qy 184 ATCGGCCAGAAGAAGCAGCAGCTGGCCCAGAGCGAGCAGCAGCAGACCCCCAAGGAGAGA 243
|| || || || ||||||| ||||| | ||||||||||||||||| || ||||||
Db 219 ATTGGGCAAAAAAAGCAGCGACTGGCAGATTCAGAGCAGCAGCAGACCCCTAAAGAGAGA 278
Qy 244 CTGAGCAGCACCCCCGGCCTGCTGAGAAGCATCTACTTCAGCAGCCCCGAGGACAGACCC 303
|| ||||| ||||| | | | || ||||||||| |||||| |||||| |
Db 279 CTCCTGTCGACCCCGGGCCTCCGGCGGAGTATCTACTTCTCCAGCCCAGAGGACCATTCT 338
Qy 304 GCCAGACTGGGGCCCGAGTATTTCGACCAGCCCGCCGTGACCCTGGCCAGAGCCTTCCTG 363
| | | || || || |||| ||| |||||||| || || ||||| ||| | || || |||
Db 339 GGCCGGCTAGGACCAGAGTTTTTTGACCAGCCAGCAGTCACCCTAGCCCGTGCATTTCTG 398
Qy 364 GGCCAGGTGCTGGTGAGAAGACTGGCCGACGGCACCGAGCTGAGAGGCAGAATCGTGGAG 423
|| ||||| || || | |||| || || || || || || | || | || ||||||
Db 399 GGACAGGTTCTTGTCCGGCGACTCGCTGATGGAACAGAACTCCGTGGGCGCATTGTGGAG 458
Qy 424 ACCGAGGCATATCTGGGCCCCGAAGATGAGGCGGCTCACAGCAGAGGGGGCAGGCAAACC 483
|| |||||||| |||| || |||||||| || |||||| ||||| ||| |||| |||
Db 459 ACTGAGGCATACTTGGGGCCAGAAGATGAAGCTGCTCACTCAAGAGGTGGCCGGCAGACC 518
Qy 484 CCCAGAAACAGAGGCATGTTCATGAAGCCCGGCACCCTGTACGTGTACCTGATCTACGGC 543
||| | ||| | |||||||||||||| || || |||||||| |||||||| ||||| |||
Db 519 CCCCGGAACCGTGGCATGTTCATGAAACCTGGGACCCTGTATGTGTACCTCATCTATGGC 578
Qy 544 ATGTACTTCTGCCTGAACGTATCCTCCCAGGGCGCAGGTGCGTGTGTGCTGCTGAGAGCC 603
|||||||||||| |||| || || || || || || || ||||| |||| |||||
Db 579 ATGTACTTCTGCTTGAATGTCTCTAGTCAAGGGGCTGGGGCTTGTGTCTTGCTAAGAGCA 638
Qy 604 CTGGAGCCCCTGGAGGGCCTGGAGACCATGAGACAGCTGAGAAACAGCCTGAGAAAGAGC 663
|| ||||||||||||||||||||||||||| | ||||| | ||| ||| |||| |||
Db 639 CTAGAGCCCCTGGAGGGCCTGGAGACCATGCGGCAGCTTCGTAACTCCCTCCGAAAAAGC 698
Qy 664 ACCGTGGGCAGAAGCCTGAAGGACAGAGAGCTGTGCAACGGCCCCAGCAAGCTGTGCCAG 723
|| || ||| | ||| |||||| | || || || | || ||| |||||||||||||
Db 699 ACTGTCGGCCGTTCCCTCAAGGACCGTGAACTCTGTAGTGGTCCCTCCAAGCTGTGCCAG 758
Qy 724 GCCCTGGCCATCGACAAGAGCTTCGACCAGAGAGACTTAGCCCAGGACGAGGCTGTGTGG 783
||||||||||| || |||||||| |||||| ||||| | || || || || |||||||||
Db 759 GCCCTGGCCATTGATAAGAGCTTTGACCAGCGAGACCTGGCTCAAGATGATGCTGTGTGG 818
Qy 784 CTGGAACACGGGCCCCTGGAAAGCAGCAGCCCGGC---GGTGGTGGCCGCTGCCAGAATC 840
||||| || || || ||||| ||| ||||| || ||||||||| || ||| | ||
Db 819 CTGGAGCATGGCCCTCTGGAGTCCAGTAGCCCAGCTGTGGTGGTGGCAGCAGCCCGTATA 878
Qy 841 GGCATCGGCCACGCCGGCGAGTGGACCCAGAAGCCCCTGAGATTCTACGTGCAGGGCAGC 900
|| || || || || || |||||||| ||||||||| || | ||||| || |||||||||
Db 879 GGTATTGGTCATGCAGGGGAGTGGACACAGAAGCCCTTGCGCTTCTATGTCCAGGGCAGC 938
Qy 901 CCCTGGGTGAGCGTCGTAGACAGAGTGGCCGAGCAGATGTACCAGCCCCAGCAGACCGCC 960
|| ||||| || || |||||||||||||| || |||||| | ||||| ||||| || |||
Db 939 CCATGGGTCAGTGTGGTAGACAGAGTGGCTGAACAGATGGATCAGCCTCAGCAAACAGCC 998
Qy 961 TGCAGCGA 968
||| ||
Db 999 TGCTCTGA 1006
Similarly, the same sequence is the closest prior art to SEQ ID NOs: 3 (61.9% overall identity; omitted for brevity, see search results in SCV). Analysis of the codon usage did not show consistent codon usage patterns indicative of standard codon optimization.
Conclusion
No claim is allowed at this time.
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/AMANDA M ZAHORIK/Examiner, Art Unit 1636
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