DETAILED ACTION
Status of the Application
Claims 1-18, 20, 24-33 are pending.
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
A preliminary amendment of claim 20, cancellation of claim 21 and addition of claims 24-33 as submitted in a communication filed on 1/27/2026 is acknowledged.
Applicant’s election with traverse of Group 45, claims 20-21, drawn in part to a process for the production of beta-alanine, wherein said process requires providing a host cell that expresses a variant of the polypeptide of SEQ ID NO: 29, as submitted in a communication filed on 1/27/2026 is acknowledged.
Applicant’s traverse is on the grounds that claims 20, 24-33 share a unifying inventive concept related to the discovery that N-terminally truncated insect ADC enzymes exhibit increased conversion of aspartate to beta-alanine. Applicant also argues that these claims require the positions at which the N-terminal truncations are contemplated. Applicant states that Barnhart et al. do not teach these inventive concepts. Applicant states that since claim 1 was identified as a potential linking claim, claim 20 should be considered a linking claim. Applicant’s arguments have been fully considered but not deemed persuasive to withdraw the restriction requirement. The Examiner acknowledges the teachings of the specification regarding the effect of deleting a segment of an ADC enzyme. However, contrary to Applicant’s assertions, the technical feature linking the inventions is an insect ADC protein, which is clearly taught by Barnhart et al. Please note that in the absence of a specific structural limitation associated the “truncated” enzyme, the term “truncated” does not convey a specific structural feature to distinguish between a “truncated” protein and one that is not. For example, a gene can encode several isoforms of a protein, where the isoforms are fragments of the longest protein encoded by the gene, including an isoform that lacks a section of the N-terminus of the longest protein encoded by the gene. With regard to the argument that claim 20 should be considered a linking claim, it is noted that claim 20 is not a generic linking claim but rather a Markush claim in view of the recitation of items (a)-(n). Claim 1 does not recite any of the limitations in the Markush group of (a)-(n). The requirement is deemed proper and therefore is made FINAL.
Claims 1-18 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 1/27/2026.
Claims 20, 24-33 are at issue and will be examined only to the extent they encompass the elected invention.
Specification
The title of the invention is not descriptive. A new title is required that is clearly indicative of the invention to which the claims are directed. The invention of claims 20, 24-33 is directed to a process for the production of beta-alanine. Appropriate correction is required.
The specification is objected for not complying with sequence rules. While Figures 2-3 display alignments of several sequences, neither the drawings nor the Brief Description of the Drawings indicate the corresponding sequence identifiers. Applicant is required to insert the corresponding sequence identifiers in the Brief Description of the Drawings or amend the drawings to include the sequence identifiers in front of each sequence. See particularly 37 CFR 1.821(d). Appropriate correction is required.
Priority
Acknowledgment is made of a claim for foreign priority under 35 U.S.C. 119(a)-(d) to PCT/CN2021/078949 filed on 03/03/2021. Receipt is acknowledged of papers submitted under 35 U.S.C. 119(a)-(d), which papers have been placed of record in the file.
This is the US national application which entered the national stage from 371 of PCT/CN2022/079042 filed on 03/03/2022.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 7/11/2025 and 8/29/2023 are acknowledged. The submissions are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements have been considered by the examiner.
Drawings
The drawings submitted on 8/29/2023 have been reviewed and are accepted by the Examiner for examination purposes.
Claim Objections
Claim 24 is objected to due to the recitation of “or which is a truncated variant of a wild-type ADC enzyme, the wild-type ADC enzyme being defined by an amino acid sequence at least 90,…or 99% identical overall to the amino acid sequence of SEQ ID NO: 29”. To enhance clarity and to be consistent with commonly used claim language, the term should be amended to recite “or wherein the recombinant truncated insect ADC is a truncated variant of a wild-type ADC enzyme having an amino acid sequence at least 90…99% identical to the amino acid sequence of SEQ ID NO: 29”. Appropriate correction is required.
Claim 25 is objected to due to the recitation of “from the genus: Culex…” The colon should be removed between “genus” and “Culex”. Appropriate correction is required.
Claim 26 is objected to due to the recitation of “from the species: Culex…” The colon should be removed between “species” and “Culex”. Appropriate correction is required.
Claim Rejections - 35 USC § 112(b) or Second Paragraph (pre-AIA )
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 20, 24-33 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 pre-AIA the applicant regards as the invention.
Claim 20 (claims 24-33 dependent thereon) is indefinite in the recitation of “lacking a sufficient number of contiguous residues within the amino terminal region of a corresponding full length wild-type insect ADC..” for the following reasons. First, it is unclear if the contiguous residues missing include the N-terminal amino acid full length wild-type insect ADC, or if the contiguous residues do not necessarily include the N-terminal amino acid of the full-length wild-type insect ADC. Second, the term “sufficient” is a relative term and the claim fails to provide the basis for comparison to determine how many contiguous amino acids are “sufficient”. Correction is required.
Claim 20 (claims 24-33 dependent thereon) is indefinite in the recitation of “wherein the recombinant truncated insect ADC enzyme is truncated at a position N-terminal (upstream) of a residue corresponding to any one of: (a) position 75 of the amino acid sequence of CtADC set forth in SEQ ID NO: 2….(n) position 1 to 491 the amino acid sequence set forth in SEQ ID NO: 29” for the following reasons. As written, it is unclear if the claim requires the recombinant truncated enzyme to lack all the amino acids of the wild type ADC from the N-terminal amino acid to the amino acid that corresponds to position X of the amino acid sequence set forth in SEQ ID NO: Y, such as a variant that consists of all of SEQ ID NO: 2 except for amino acids 1-75 of the protein of SEQ ID NO: 2, or a variant that consists of all of SEQ ID NO: 4 except for amino acids 1-82 of the protein of SEQ ID NO: 4. In addition, the term “wherein the recombinant truncated insect ADC enzyme is truncated at a position N-terminal (upstream) of a residue corresponding to ….(n) position 1 to 491 the amino acid sequence set forth in SEQ ID NO: 29” is completely unclear and confusing because position 1 to 491 is not a single position, therefore there is no single residue that corresponds to positions 1-491, which is the entire SEQ ID NO: 29. In addition, even if one were to interpret the term to encompass a truncated variant that lacks a fragment from the N-terminal amino acid up to any of the amino acids 1-491 of the polypeptide of SEQ ID NO: 29, it would be unclear as to how such truncated variant would lack nothing in the case of position 1. For examination purposes, claim 20 will be interpreted as directed to a process for the production of beta-alanine, wherein said process comprises providing an asparate-1-decarboxylase (ADC) and contacting said ADC with a source of aspartate, wherein said ADC can be an insect ADC, or a truncated variant of an insect ADC. Correction is required.
Claim 30 is indefinite in the recitation of “wherein X is any integer between 5 and 50” for the following reasons. As indicated above with regard to claim 20, it is unclear if the truncated ADC is required to lack, for example, amino acids 1-75 of the polypeptide of SEQ ID NO: 2, or amino acids 1-82 of the polypeptide of SEQ ID NO: 4. Therefore, requiring the deletion to be of 5 to 50 contiguous amino acids is not within the scope of claim 20, from which claim 30 depends. Claim 30 is broader in scope thus not further limiting claim 20, from which it depends Correction is required.
Claim 31 is indefinite in the recitation of “wherein the truncation occurs at a position immediately C-terminal of a residue corresponding to position n of a full-length wild-type insect ADC, wherein n is any integer between 2 and Y, wherein Y is the most C-terminal residue position within the full-length wild-type insect ADC at which truncation from the N-terminus can occur..” for the following reasons. Claim 20 appears to require a truncated ADC enzyme wherein the truncated enzyme is missing a fragment of the N-terminus of the wild-type ADC. Claim 31 appears to require a truncation such that the truncated enzyme is missing a fragment of the C-terminus of the wild-type ADC. Therefore, it is unclear as to where the truncation should be, either the N-terminus or C-terminus of the wild-type ADC. In addition, the term “wherein Y is the most C-terminal residue position within the full-length wild-type insect ADC at which truncation from the N-terminus can occur” is completely unclear and confusing because one cannot determine what a most C-terminal residue at which truncation from the N-terminus can occur is. For examination purposes, claim 31 will be interpreted as a duplicate of claim 20 as interpreted above. Correction is required.
Claim 32 is indefinite in the recitation of “The process of claim 20, the truncation occurs at a position C-terminal …of a residue corresponding to any one of (a) position 2, 3, 4….of the amino acid sequence of CtADC set forth in SEQ ID NO: 2….(n) position 1 to 491 the amino acid sequence set forth in SEQ ID NO: 29” for the following reasons. As indicated above, it appears from claim 20 that the truncated enzyme is one that lacks a segment of the N-terminus of the wild-type ADC. If the intended phrase in claim 32 is “The process of claim 20, wherein the truncation occurs”, such phrase would indicate that the truncation is at the C-terminus of the wild-type ADC. Therefore, it is unclear as to where the truncation should be, either the N-terminus or C-terminus of the wild-type ADC. For example, as written, claim 32 appears to require a truncated variant of the polypeptide of SEQ ID NO: 2, wherein all the amino acids after amino acid 2 are removed so that the truncated variant only comprises the first two amino acids of SEQ ID NO: 2 because the truncation would occur at position 2 of the amino acid sequence of SEQ ID NO: 2. This is confusing because claim 20 appears to require, for example, a truncated ADC that lacks amino acids 1-75 of the polypeptide of SEQ ID NO: 2, or amino acids 1-82 of the polypeptide of SEQ ID NO: 4. In addition, the term “the truncation occurs at a position C-terminal …of a residue corresponding to ….(n) position 1 to 491 the amino acid sequence set forth in SEQ ID NO: 29” is completely unclear and confusing because positions 1-491 is not a single position, therefore there is no single residue that corresponds to positions 1-491, which is the entire SEQ ID NO: 29. For examination purposes, claim 32 will be interpreted as a duplicate of claim 20 as interpreted above. Correction is required.
Claim Rejections - 35 USC § 112(a) or First Paragraph (pre-AIA )
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 20, 24-33 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
As stated in MPEP 2111.01, during examination, the claims must be interpreted as broadly as their terms reasonably allow. Claims 20, 24-33 are directed in part to a process for the production of beta alanine which requires a genus of aspartate decarboxylases (ADC) having essentially any structure, and ADCs having at least 80% sequence identity to the polypeptide of SEQ ID NO: 29. See Claim Rejections - 35 USC § 112(b) or Second Paragraph (pre-AIA ) for claim 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.
There is either (a) no structural limitation, or (b) a significant amount of structural variability with respect to the members of the genus of proteins required by the claimed process. While the specification in the instant application discloses the structure of a limited number of species of the recited genus of insect ADCs, it provides no clue as to the structural elements required in any insect ADC or any truncated variant of an insect ADC as required by the claimed process. The specification is silent with regard to the structural elements required in an insect ADC as recited in the claims. No disclosure of a structure/function correlation has been provided which would allow one of skill in the art to recognize which proteins are insect ADCs or the structural features found in an insect ADC not found in other ADCs.
The claims encompass a large genus of proteins which are structurally unrelated or substantially unrelated. A polypeptide having at least 80% sequence identity with the polypeptide of SEQ ID NO: 29 allows for any combination of 99 amino acid modifications within SEQ ID NO: 29 (99 = 0.2x491; SEQ ID NO: 29 has 491 amino acids). In view of the fact that the polypeptide of SEQ ID NO: 29 has 270 undefined amino acids (Xaa) and 221 defined amino acids, these 99 amino acid modifications would have to be present within the 221 defined amino acids. As such, a variant having at least 80% sequence identity to the polypeptide of SEQ ID NO: 29 would only have 122 defined amino acids (122 = 221-99) and 369 undefined amino acids (369 = 491-122). That is equivalent to a variant having 24.8% sequence identity to a protein where 491 amino acids are fully defined (24.8% = 122x100/491). The total number of variants of a polypeptide having a specific number of amino acid substitutions can be calculated from the formula N!x19A/(N-A)!/A!, where N is the length in amino acids of the reference polypeptide and A is the number of allowed substitutions. Thus, for a variant of the polypeptide of SEQ ID NO: 29 having at least 80% sequence identity to SEQ ID NO: 29, the total number of variants that result from amino acid substitutions is 491!x19369/(491-369)!/369! or 1.07x10590 variants. A sufficient written description of a genus of polypeptides may be achieved by a recitation of a representative number of polypeptides defined by their amino acid sequence or a recitation of structural features common to members of the genus, which features constitute a substantial portion of the genus. However, in the instant case, there is either no recited structural feature which is representative of all the members of the genus of ADCs recited in the claim, or the recited structural feature, i.e., 80% sequence identity to SEQ ID NO: 29, is not representative of all the members of the genus of insect ADCs recited since there is no information as to which of the defined amino acids within the polypeptide of SEQ ID NO: 29 are essential in an insect ADC having the recited activity, which are the remaining structural elements required in the recited polypeptides in addition to those recited in the claims such that the desired ADC activity is displayed, or a correlation between structure and function which would provide those unknown structural features. Furthermore, while one could argue that the few species disclosed are representative of the structure of all the members of the genus, it is noted that the art teaches several examples of how even highly structurally homologous polypeptides can have different enzymatic activities. For example, Witkowski et al. (Biochemistry 38:11643-11650, 1999) teach that one conservative amino acid substitution transforms a β-ketoacyl synthase into a malonyl decarboxylase and completely eliminates β-ketoacyl synthase activity. Tang et al. (Phil Trans R Soc B 368:20120318, 1-10, 2013) teach that two Dehalobacter reductive dehalogenases, CfrA and DcrA, having 95.2% sequence identity to teach other have exclusively different substrate (Abstract; page 7, left column, Discussion, CfrA and DcrA). Seffernick et al. (J. Bacteriol. 183(8):2405-2410, 2001) teach that two naturally occurring Pseudomonas enzymes having 98% amino acid sequence identity catalyze two different reactions: deamination and dehalogenation, therefore having different function. Therefore, since minor structural differences may result in changes affecting function, and no additional information correlating structure with the desired functional characteristics has been provided, one cannot reasonably conclude that the few species disclosed are representative of the structure of all the insect ADCs required by the claims.
Due to the fact that the specification only discloses a limited number of species of the genus of insect ADCs required by the claimed process, and the lack of description of any additional species by any relevant, identifying characteristics or properties, one of skill in the art would not recognize from the disclosure that Applicant was in possession of the claimed invention.
Claims 20, 24-33 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for a process for the production of beta alanine, wherein said process requires contacting aspartate with a variant of the polypeptide of SEQ ID NO: 2 having ADC activity, wherein said variant comprises all of SEQ ID NO: 2 except for (a) amino acids 1-11 of SEQ ID NO: 2, (b) amino acids 1-21 of SEQ ID NO: 2, (c) amino acids 1-31 of SEQ ID NO: 2, (d) amino acids 1-41 of SEQ ID NO: 2, (e) amino acids 1-51 of SEQ ID NO: 2 (f) amino acids 1-61 of SEQ ID NO: 2, or (g) amino acids 1-711 of SEQ ID NO: 2, does not reasonably provide enablement for a process for the production of beta alanine, wherein said process requires contacting aspartate with any insect ADC, a protein comprising SEQ ID NO: 29, any variant of an insect ADC that results from deleting any number of amino acids from the N-terminus of an insect ADC, or any variant of the protein of SEQ ID NO: 29 that results from deleting any number of amino acids from the N-terminus of the protein of SEQ ID NO: 29. 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 these claims.
Factors to be considered in determining whether undue experimentation is required are summarized in In re Wands (858 F.2d 731, 737, 8 USPQ2nd 1400 (Fed. Cir. 1988)) as follows: 1) quantity of experimentation necessary, 2) the amount of direction or guidance presented, 3) the presence and absence of working examples, 4) the nature of the invention, 5) the state of 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 claims. The factors which have led the Examiner to conclude that the specification fails to teach how to make and/or use the claimed invention without undue experimentation, are addressed in detail below.
The breadth of the claims. Claims 20, 24-33 broadly encompass a process for producing beta alanine that requires contacting aspartate with ADC enzymes having essentially any structure, ADC enzymes having at least 80% sequence identity to the polypeptide of SEQ ID NO: 29, any insect ADC, any variant of an insect ADC that results from deleting any number of amino acids from the N-terminus of an insect ADC, or any variant of the protein of SEQ ID NO: 29 that results from deleting any number of amino acids from the N-terminus of the protein of SEQ ID NO: 29. See Claim Rejections - 35 USC § 112(b) or Second Paragraph (pre-AIA ) for claim interpretation.
The enablement provided is not commensurate in scope with the claims due to the extremely large number of proteins of unknown structure encompassed by the claims, and the lack of information regarding the structural elements which are required in any of the ADCs required by the claims. In the instant case, the specification enables a process for the production of beta alanine, wherein said process requires contacting aspartate with a variant of the polypeptide of SEQ ID NO: 2 having ADC activity, wherein said variant comprises all of SEQ ID NO: 2 except for (a) amino acids 1-11 of SEQ ID NO: 2, (b) amino acids 1-21 of SEQ ID NO: 2, (c) amino acids 1-31 of SEQ ID NO: 2, (d) amino acids 1-41 of SEQ ID NO: 2, (e) amino acids 1-51 of SEQ ID NO: 2 (f) amino acids 1-61 of SEQ ID NO: 2, or (g) amino acids 1-711 of SEQ ID NO: 2.
The amount of direction or guidance presented and the existence of working examples. The specification discloses the amino acid sequence of a limited number of insect ADC proteins as working examples. However, the specification fails to provide any clue as to the structural elements required in any insect ADC or variant thereof that can be used in the claimed process, including which structural features within the proteins disclosed by the specification are required in any insect ADC or those structural features which are specific to insect ADCs not found in other ADCs. Moreover, while the polypeptide of SEQ ID NO: 29 has 270 amino acids that are variable, it is unclear if the remaining 221 defined amino acids is all that is required to have an insect ADC. In addition, while the claims require variants of the polypeptide of SEQ ID NO: 29 having at least 80% sequence identity to the polypeptide of SEQ ID NO: 29, it is unclear as to which of the 221 amino acids that are defined can be modified or which are the 122 amino acids that must be present to have a variant with ADC activity. No correlation between structure and function has been presented.
The state of prior art, the relative skill of those in the art, and the predictability or unpredictability of the art. The amino acid sequence of a polypeptide determines its structural and functional properties. While the art discloses a limited number of insect ADCs, neither the specification nor the art provide a correlation between structure and function such that one of skill in the art can envision the structure of any insect ADC that can be used in the claimed process. In addition, the art does not provide any teaching or guidance as to which variants having at least 80% sequence identity to the proteins recited are proteins with ADC activity. The art clearly teaches that (a) determining function based solely on structural homology, and (b) modification of a protein’s amino acid sequence to obtain the desired activity without any guidance/knowledge as to which amino acids in a protein are tolerant of modification and which ones are conserved are highly unpredictable. For example, Singh et al. (Current Protein and Peptide Science 19(1):5-15, 2018) disclose different protein engineering approaches and state that despite the availability of an ever-growing database of protein structures and highly sophisticated computational algorithms, protein engineering is still limited by the incomplete understanding of protein functions, folding, flexibility and conformational changes (page 11, left column, last paragraph). Sadowski et al. (Current Opinion in Structural Biology 19:357-362, 2009) teach that much of the problem in assigning function from structure comes from functional convergence, where although a stable structure is required to perform many functions it is not always necessary to adopt a particular structure to carry out a particular function (page 357, right column, first full paragraph). Sadowski et al. further explain that the unexpected and significant difficulties of predicting function from structure show that the potential of structural models for providing novel functional annotations has not yet fully realized. Sadowski et al. also states that while a few successes have been achieved which required manual intervention, the ability to vary the requirements for specificity in prediction means that it is difficult to determine how useful the end result may be for the user (page 361, left column, first full paragraph). The teachings of Singh et al. and Sadowski et al. are further supported by the teachings of Witkowski et al., Tang et al. and Seffernick et al. already discussed above, where it is shown that even small amino acid changes result in enzymatic activity changes.
The quantity of experimentation required to practice the claimed invention based on the teachings of the specification. While methods of generating or isolating variants of a polypeptide and enzymatic assays were known in the art at the time of the invention, it was not routine in the art to screen by a trial and error process for an essentially infinite number of proteins to find a protein with ADC activity which can be used in a process as claimed. In the absence of (i) a rational and predictable scheme for selecting those proteins most likely to have the desired functional features, and/or (ii) a correlation between structure and ADC activity, one of skill in the art would have to test an essentially infinite number of proteins to determine which ones have the desired functional characteristics.
Therefore, taking into consideration the extremely broad scope of the claim, the lack of guidance, the amount of information provided, the lack of knowledge about a correlation between structure and the desired function, and the high degree of unpredictability of the prior art in regard to structural changes and their effect on function, one of ordinary skill in the art would have to go through the burden of undue experimentation in order to practice the claimed invention. Thus, Applicant has not provided sufficient guidance to enable one of ordinary skill in the art to make and use the invention in a manner reasonably correlated with the scope of the claims.
Claim Rejections - 35 USC § 103 (AIA )
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 of this title, 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.
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.
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.
Claims 20, 24-28, 31-33 are rejected under 35 U.S.C. 103 as being unpatentable over Liu et al. (Aplied Microbiology and Biotechnology 103:9443-9453, 2019) in view of Adams et al. (GenBank accession No. AHN54424 4/22/2019, herein after Adams 1) and Barnhart et al. (U.S. Publication No. 2016/0168600 6/16/2016; cited in the IDS) as evidenced by Adams et al. (Genbank accession No. AFH03699 4/20/2020, hereinafter Adams 2).
Liu et al. teach a process for the production of beta-alanine that requires contacting a whole E. coli cell that produces an insect ADH (from T. castaneum) with aspartate to produce beta-alanine (page 9447, right column, Whole-cell catalysis using E. coli expressing recombinant TcCSADC-page 9448 and Figure 4). Liu et al. teach using HPLC to detect beta-alanine, thus teaching isolation of the beta-alanine produced (page 9445, left column Determination of the activity and kinetic parameters of TcCSADC). Liu et al. teach that research on ADCs from insects has indicated that the activity of these ADCs from eukaryotes is much higher than the activity of ADCs from prokaryotes (page 9444, left column, second full paragraph). Liu et al. do not teach an ADC from D. melanogaster.
Adams 1 discloses a D. melanogaster ADC that comprises 514 amino acids which is a truncated version of another D. melanogaster ADC having 575 amino acids as evidenced by Adams 2. Adams 1 teach that this ADC belongs to EC 4.1.1.11 and has aspartate decarboxylase activity (see entry for Protein and CDS). As shown in the alignment below, the protein of Adams 1 consists of amino acids 62-575 of the protein of Adams 2. Therefore, the protein of Adams 1 is a truncated variant of the D. melanogaster ADC of Adams 2 that lacks amino acids 1-61. The protein of Adams 2 is identical to the polypeptide of SEQ ID NO: 8 of the instant application. Therefore, the wild-type ADC is at least 99% sequence identical to the polypeptide of SEQ ID NO: 8. As shown in the alignment below, the protein of Adams 1 (truncated variant) is 95.1% sequence identical to the polypeptide of SEQ ID NO: 29 because there are 268 positions in the protein of SEQ ID NO: 29 that can be any amino acid which would match the corresponding 268 positions in the protein of Adams 1 in addition to 199 matches with defined amino acids (95.1% = (199 + 268)x100/491; SEQ ID NO: 29 has 491 amino acids). As shown in the alignment below, the protein of Adams 2 (wild-type ADC) is 95.1% sequence identical to the polypeptide of SEQ ID NO: 29 because there are 268 positions in the protein of SEQ ID NO: 29 that can be any amino acid which would match the corresponding 268 positions in the protein of Adams 2 in addition to 199 matches with defined amino acids (95.1% = (199 + 268)x100/491; SEQ ID NO: 29 has 491 amino acids).
Barnhart et al. teach that there is an improved production of 3-hydroxypropionic acid (3-HP) in host cells when an ADC from insects is used (page 1, paragraph [0009]). Barnhart et al. teach that 3-HP is produced from beta alanine as a precursor (Figure 1). Barnhart et al. teach that ADC is an enzyme that catalyzes the conversion of aspartate to beta alanine and belongs to EC 4.1.1.11 (page 3, paragraph [0048]) and that the ADC can be from Drosophila, including Drosophila melanogaster (page 7, paragraph [0091]). Barnhart et al. do not teach the D. melanogaster ADC of Adams 1.
Claims 20, 24-28, 31-33 are directed in part to a process for the production of beta-alanine that requires (i) contacting an ADH, wherein said ADH is a truncated variant of a wild-type insect ADH, wherein said wild-type insect ADH is from Drosophila melanogaster, and wherein said truncated variant catalyzes the conversion of aspartate to beta-alanine, and (ii) isolating the beta-alanine produced, wherein said wild-type insect ADH is at least 95% sequence identical to the polypeptide of SEQ ID NO: 8 or the polypeptide of SEQ ID NO: 29, wherein said truncated variant is at least 95% identical to the polypeptide of SEQ ID NO: 29, and wherein the truncated variant can be comprised in an intact host cell. See Claim Rejections - 35 USC § 112(b) or Second Paragraph (pre-AIA ) for claim interpretation.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to replace the ADC of Adams 1 in the process of Liu et al. A person of ordinary skill in the art is motivated to use the ADC of Adams 1 because Liu et al. teach that insect ADCs have been shown to have a higher enzymatic activity compared to prokaryotic ADCs, and Barnhart et al. clearly suggest that insect ADCs such as those from D. melanogaster appear to have increased enzymatic activity in view of the enhanced production of a compound that requires the conversion of aspartate to beta alanine. The use of the protein of Adams 1 is merely a replacement with a functional equivalent as evidenced by the fact that the protein of Adams 1 belongs to EC 4.1.1.11. One of ordinary skill in the art has a reasonable expectation of success at using the ADC of Adams 1 in the process of Liu et al. because the protein of Adams 1 has the exact same enzymatic activity as that of the enzyme in the process of Liu et al. Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention.
SEQ ID NO: 8
X2J8B3_DROME
ID X2J8B3_DROME Unreviewed; 514 AA.
AC X2J8B3;
DT 11-JUN-2014, integrated into UniProtKB/TrEMBL.
DT 11-JUN-2014, sequence version 1.
DT 08-OCT-2025, entry version 77.
DE SubName: Full=Black, isoform C {ECO:0000313|EMBL:AHN54424.1};
DE EC=4.1.1.- {ECO:0000313|EMBL:AHN54424.1};
DE EC=4.1.1.11 {ECO:0000313|EMBL:AHN54424.1};
DE EC=4.1.1.15 {ECO:0000313|EMBL:AHN54424.1};
GN Name=Adc {ECO:0000313|FlyBase:FBgn0000153};
GN Synonyms=ADC {ECO:0000313|EMBL:AHN54424.1}, anon-34Db
GN {ECO:0000313|EMBL:AHN54424.1}, B {ECO:0000313|EMBL:AHN54424.1}, b
GN {ECO:0000313|EMBL:AHN54424.1}, BG:DS00941.5
GN {ECO:0000313|EMBL:AHN54424.1}, Black {ECO:0000313|EMBL:AHN54424.1},
GN cDNA 1 {ECO:0000313|EMBL:AHN54424.1}, DGad2
GN {ECO:0000313|EMBL:AHN54424.1}, Dmel\CG7811
GN {ECO:0000313|EMBL:AHN54424.1}, DmGad2 {ECO:0000313|EMBL:AHN54424.1},
GN Gad2 {ECO:0000313|EMBL:AHN54424.1}, GAD[[2]]
GN {ECO:0000313|EMBL:AHN54424.1};
GN ORFNames=CG7811 {ECO:0000313|EMBL:AHN54424.1,
GN ECO:0000313|FlyBase:FBgn0000153}, Dmel_CG7811
GN {ECO:0000313|EMBL:AHN54424.1};
OS Drosophila melanogaster (Fruit fly).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota;
OC Neoptera; Endopterygota; Diptera; Brachycera; Muscomorpha; Ephydroidea;
OC Drosophilidae; Drosophila; Sophophora.
OX NCBI_TaxID=7227 {ECO:0000313|EMBL:AHN54424.1, ECO:0000313|Proteomes:UP000000803};
RN [1] {ECO:0000313|EMBL:AHN54424.1, ECO:0000313|Proteomes:UP000000803}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Berkeley {ECO:0000313|Proteomes:UP000000803};
RX PubMed=10731132; DOI=10.1126/science.287.5461.2185;
RA Adams M.D., Celniker S.E., Holt R.A., Evans C.A., Gocayne J.D.,
RA Amanatides P.G., Scherer S.E., Li P.W., Hoskins R.A., Galle R.F.,
RA George R.A., Lewis S.E., Richards S., Ashburner M., Henderson S.N.,
RA Sutton G.G., Wortman J.R., Yandell M.D., Zhang Q., Chen L.X., Brandon R.C.,
RA Rogers Y.H., Blazej R.G., Champe M., Pfeiffer B.D., Wan K.H., Doyle C.,
RA Baxter E.G., Helt G., Nelson C.R., Gabor G.L., Abril J.F., Agbayani A.,
RA An H.J., Andrews-Pfannkoch C., Baldwin D., Ballew R.M., Basu A.,
RA Baxendale J., Bayraktaroglu L., Beasley E.M., Beeson K.Y., Benos P.V.,
RA Berman B.P., Bhandari D., Bolshakov S., Borkova D., Botchan M.R., Bouck J.,
RA Brokstein P., Brottier P., Burtis K.C., Busam D.A., Butler H., Cadieu E.,
RA Center A., Chandra I., Cherry J.M., Cawley S., Dahlke C., Davenport L.B.,
RA Davies P., de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I.,
RA Dietz S.M., Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C.,
RA Dunn P., Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S.,
RA Fleischmann W., Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M.,
RA Glasser K., Glodek A., Gong F., Gorrell J.H., Gu Z., Guan P., Harris M.,
RA Harris N.L., Harvey D., Heiman T.J., Hernandez J.R., Houck J., Hostin D.,
RA Houston K.A., Howland T.J., Wei M.H., Ibegwam C., Jalali M., Kalush F.,
RA Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A., Kimmel B.E., Kodira C.D.,
RA Kraft C., Kravitz S., Kulp D., Lai Z., Lasko P., Lei Y., Levitsky A.A.,
RA Li J., Li Z., Liang Y., Lin X., Liu X., Mattei B., McIntosh T.C.,
RA McLeod M.P., McPherson D., Merkulov G., Milshina N.V., Mobarry C.,
RA Morris J., Moshrefi A., Mount S.M., Moy M., Murphy B., Murphy L.,
RA Muzny D.M., Nelson D.L., Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R.,
RA Pacleb J.M., Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V.,
RA Reese M.G., Reinert K., Remington K., Saunders R.D., Scheeler F., Shen H.,
RA Shue B.C., Siden-Kiamos I., Simpson M., Skupski M.P., Smith T., Spier E.,
RA Spradling A.C., Stapleton M., Strong R., Sun E., Svirskas R., Tector C.,
RA Turner R., Venter E., Wang A.H., Wang X., Wang Z.Y., Wassarman D.A.,
RA Weinstock G.M., Weissenbach J., Williams S.M., WoodageT, Worley K.C.,
RA Wu D., Yang S., Yao Q.A., Ye J., Yeh R.F., Zaveri J.S., Zhan M., Zhang G.,
RA Zhao Q., Zheng L., Zheng X.H., Zhong F.N., Zhong W., Zhou X., Zhu S.,
RA Zhu X., Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M., Venter J.C.;
RT "The genome sequence of Drosophila melanogaster.";
RL Science 287:2185-2195(2000).
RN [2] {ECO:0000313|Proteomes:UP000000803}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Berkeley {ECO:0000313|Proteomes:UP000000803};
RX PubMed=12537568;
RA Celniker S.E., Wheeler D.A., Kronmiller B., Carlson J.W., Halpern A.,
RA Patel S., Adams M., Champe M., Dugan S.P., Frise E., Hodgson A.,
RA George R.A., Hoskins R.A., Laverty T., Muzny D.M., Nelson C.R.,
RA Pacleb J.M., Park S., Pfeiffer B.D., Richards S., Sodergren E.J.,
RA Svirskas R., Tabor P.E., Wan K., Stapleton M., Sutton G.G., Venter C.,
RA Weinstock G., Scherer S.E., Myers E.W., Gibbs R.A., Rubin G.M.;
RT "Finishing a whole-genome shotgun: release 3 of the Drosophila melanogaster
RT euchromatic genome sequence.";
RL Genome Biol. 3:RESEARCH0079-RESEARCH0079(2002).
RN [3] {ECO:0000313|Proteomes:UP000000803}
RP GENOME REANNOTATION.
RC STRAIN=Berkeley {ECO:0000313|Proteomes:UP000000803};
RX PubMed=12537572; DOI=10.1186/gb-2002-3-12-research0083;
RA Misra S., Crosby M.A., Mungall C.J., Matthews B.B., Campbell K.S.,
RA Hradecky P., Huang Y., Kaminker J.S., Millburn G.H., Prochnik S.E.,
RA Smith C.D., Tupy J.L., Whitfield E.J., Bayraktaroglu L., Berman B.P.,
RA Bettencourt B.R., Celniker S.E., de Grey A.D.N.J., Drysdale R.A.,
RA Harris N.L., Richter J., Russo S., Schroeder A.J., Shu S.Q., Stapleton M.,
RA Yamada C., Ashburner M., Gelbart W.M., Rubin G.M., Lewis S.E.;
RT "Annotation of the Drosophila melanogaster euchromatic genome: a systematic
RT review.";
RL Genome Biol. 3:RESEARCH0083.1-RESEARCH0083.22(2002).
RN [4] {ECO:0000313|Proteomes:UP000000803}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Berkeley {ECO:0000313|Proteomes:UP000000803};
RX PubMed=12537573;
RA Kaminker J.S., Bergman C.M., Kronmiller B., Carlson J., Svirskas R.,
RA Patel S., Frise E., Wheeler D.A., Lewis S.E., Rubin G.M., Ashburner M.,
RA Celniker S.E.;
RT "The transposable elements of the Drosophila melanogaster euchromatin: a
RT genomics perspective.";
RL Genome Biol. 3:RESEARCH0084.1-RESEARCH0084.20(2002).
RN [5] {ECO:0000313|EMBL:AHN54424.1, ECO:0000313|Proteomes:UP000000803}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Berkeley {ECO:0000313|Proteomes:UP000000803};
RX PubMed=12537574;
RA Hoskins R.A., Smith C.D., Carlson J.W., Carvalho A.B., Halpern A.,
RA Kaminker J.S., Kennedy C., Mungall C.J., Sullivan B.A., Sutton G.G.,
RA Yasuhara J.C., Wakimoto B.T., Myers E.W., Celniker S.E., Rubin G.M.,
RA Karpen G.H.;
RT "Heterochromatic sequences in a Drosophila whole-genome shotgun assembly.";
RL Genome Biol. 3:RESEARCH0085-RESEARCH0085(2002).
RN [6] {ECO:0000313|EMBL:AHN54424.1, ECO:0000313|Proteomes:UP000000803}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Berkeley {ECO:0000313|Proteomes:UP000000803};
RX PubMed=16110336; DOI=10.1371/journal.pcbi.0010022;
RA Quesneville H., Bergman C.M., Andrieu O., Autard D., Nouaud D.,
RA Ashburner M., Anxolabehere D.;
RT "Combined evidence annotation of transposable elements in genome
RT sequences.";
RL PLoS Comput. Biol. 1:166-175(2005).
RN [7] {ECO:0000313|EMBL:AHN54424.1, ECO:0000313|Proteomes:UP000000803}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Berkeley {ECO:0000313|Proteomes:UP000000803};
RX PubMed=17569856; DOI=10.1126/science.1139815;
RA Smith C.D., Shu S., Mungall C.J., Karpen G.H.;
RT "The Release 5.1 annotation of Drosophila melanogaster heterochromatin.";
RL Science 316:1586-1591(2007).
RN [8] {ECO:0000313|EMBL:AHN54424.1, ECO:0000313|Proteomes:UP000000803}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Berkeley {ECO:0000313|Proteomes:UP000000803};
RX PubMed=17569867; DOI=10.1126/science.1139816;
RA Hoskins R.A., Carlson J.W., Kennedy C., Acevedo D., Evans-Holm M.,
RA Frise E., Wan K.H., Park S., Mendez-Lago M., Rossi F., Villasante A.,
RA Dimitri P., Karpen G.H., Celniker S.E.;
RT "Sequence finishing and mapping of Drosophila melanogaster
RT heterochromatin.";
RL Science 316:1625-1628(2007).
CC -!- COFACTOR:
CC Name=pyridoxal 5'-phosphate; Xref=ChEBI:CHEBI:597326;
CC Evidence={ECO:0000256|ARBA:ARBA00001933,
CC ECO:0000256|PIRSR:PIRSR602129-50, ECO:0000256|RuleBase:RU000382};
CC -!- SUBUNIT: Homodimer. {ECO:0000256|ARBA:ARBA00011738}.
CC -!- SIMILARITY: Belongs to the group II decarboxylase family.
CC {ECO:0000256|ARBA:ARBA00009533, ECO:0000256|RuleBase:RU000382}.
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DR EMBL; AE014134; AHN54424.1; -; Genomic_DNA.
DR RefSeq; NP_001285910.1; NM_001298981.1.
DR AlphaFoldDB; X2J8B3; -.
DR SMR; X2J8B3; -.
DR DNASU; 34791; -.
DR GeneID; 34791; -.
DR AGR; FB:FBgn0000153; -.
DR CTD; 34791; -.
DR FlyBase; FBgn0000153; Adc.
DR VEuPathDB; VectorBase:FBgn0000153; -.
DR HOGENOM; CLU_011856_0_0_1; -.
DR OrthoDB; 392571at2759; -.
DR BioGRID-ORCS; 34791; 0 hits in 3 CRISPR screens.
DR Proteomes; UP000000803; Chromosome 2L.
DR Bgee; FBgn0000153; Expressed in muscle cell in imaginal disc-derived wing and 51 other cell types or tissues.
DR ExpressionAtlas; X2J8B3; baseline and differential.
DR GO; GO:0004068; F:aspartate 1-decarboxylase activity; IMP:FlyBase.
DR GO; GO:0030170; F:pyridoxal phosphate binding; IEA:InterPro.
DR GO; GO:0019483; P:beta-alanine biosynthetic process; TAS:FlyBase.
DR GO; GO:0048066; P:developmental pigmentation; TAS:FlyBase.
DR GO; GO:0006212; P:uracil catabolic process; TAS:FlyBase.
DR GO; GO:0007632; P:visual behavior; IMP:FlyBase.
DR CDD; cd06450; DOPA_deC_like; 1.
DR FunFam; 3.40.640.10:FF:000016; Glutamate decarboxylase like 1; 1.
DR Gene3D; 3.90.1150.170; -; 1.
DR Gene3D; 3.40.640.10; Type I PLP-dependent aspartate aminotransferase-like (Major domain); 1.
DR InterPro; IPR002129; PyrdxlP-dep_de-COase.
DR InterPro; IPR015424; PyrdxlP-dep_Trfase.
DR InterPro; IPR015421; PyrdxlP-dep_Trfase_major.
DR PANTHER; PTHR45677:SF12; BLACK, ISOFORM A; 1.
DR PANTHER; PTHR45677; GLUTAMATE DECARBOXYLASE-RELATED; 1.
DR Pfam; PF00282; Pyridoxal_deC; 1.
DR SUPFAM; SSF53383; PLP-dependent transferases; 1.
PE 1: Evidence at protein level;
KW Decarboxylase {ECO:0000256|ARBA:ARBA00022793};
KW Lyase {ECO:0000256|ARBA:ARBA00023239, ECO:0000256|RuleBase:RU000382};
KW Proteomics identification {ECO:0007829|PeptideAtlas:X2J8B3};
KW Pyridoxal phosphate {ECO:0000256|ARBA:ARBA00022898,
KW ECO:0000256|PIRSR:PIRSR602129-50};
KW Reference proteome {ECO:0000313|Proteomes:UP000000803}.
FT MOD_RES 326
FT /note="N6-(pyridoxal phosphate)lysine"
FT /evidence="ECO:0000256|PIRSR:PIRSR602129-50"
SQ SEQUENCE 514 AA; 58477 MW; 2265F7539D76F377 CRC64;
Query Match 90.0%; Score 2723; Length 514;
Best Local Similarity 100.0%;
Matches 514; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 62 MLANAANNNNNNNNNITSTKDDLSSFVASHPAAEFEGFIRACVDEIIKLAVFQGTNRSSK 121
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 MLANAANNNNNNNNNITSTKDDLSSFVASHPAAEFEGFIRACVDEIIKLAVFQGTNRSSK 60
Qy 122 VVEWHEPAELRQLFDFQLREQGESQDKLRELLRETIRFSVKTGHPYFINQLYSGVDPYAL 181
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 VVEWHEPAELRQLFDFQLREQGESQDKLRELLRETIRFSVKTGHPYFINQLYSGVDPYAL 120
Qy 182 VGQWLTDALNPSVYTYEVAPLFTLMEEQVLAEMRRIVGFPNGGQGDGIFCPGGSIANGYA 241
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 VGQWLTDALNPSVYTYEVAPLFTLMEEQVLAEMRRIVGFPNGGQGDGIFCPGGSIANGYA 180
Qy 242 ISCARYRHSPESKKNGLFNAKPLIIFTSEDAHYSVEKLAMFMGFGSDHVRKIATNEVGKM 301
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 ISCARYRHSPESKKNGLFNAKPLIIFTSEDAHYSVEKLAMFMGFGSDHVRKIATNEVGKM 240
Qy 302 RLSDLEKQVKLCLENGWQPLMVSATAGTTVLGAFDDLAGISEVCKKYNMWMHVDAAWGGG 361
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 RLSDLEKQVKLCLENGWQPLMVSATAGTTVLGAFDDLAGISEVCKKYNMWMHVDAAWGGG 300
Qy 362 ALMSKKYRHLLNGIERADSVTWNPHKLLAASQQCSTFLTRHQQVLAQCHSTNATYLFQKD 421
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 ALMSKKYRHLLNGIERADSVTWNPHKLLAASQQCSTFLTRHQQVLAQCHSTNATYLFQKD 360
Qy 422 KFYDTSFDTGDKHIQCGRRADVFKFWFMWKAKGTQGLEAHVEKVFRMAEFFTAKVRERPG 481
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 361 KFYDTSFDTGDKHIQCGRRADVFKFWFMWKAKGTQGLEAHVEKVFRMAEFFTAKVRERPG 420
Qy 482 FELVLESPECTNISFWYVPPGLREMERNREFYDRLHKVAPKVKEGMIKKGSMMITYQPLR 541
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 421 FELVLESPECTNISFWYVPPGLREMERNREFYDRLHKVAPKVKEGMIKKGSMMITYQPLR 480
Qy 542 QLPNFFRLVLQNSCLEESDMVYFLDEIESLAQNL 575
||||||||||||||||||||||||||||||||||
Db 481 QLPNFFRLVLQNSCLEESDMVYFLDEIESLAQNL 514
Q24062_DROME
ID Q24062_DROME Unreviewed; 575 AA.
AC Q24062;
DT 01-NOV-1996, integrated into UniProtKB/TrEMBL.
DT 01-NOV-1996, sequence version 1.
DT 08-OCT-2025, entry version 195.
DE SubName: Full=Black, isoform A {ECO:0000313|EMBL:AAF53337.1};
DE EC=4.1.1.- {ECO:0000313|EMBL:AAF53337.1, ECO:0000313|EMBL:AFH03699.1};
DE EC=4.1.1.11 {ECO:0000313|EMBL:AAF53337.1, ECO:0000313|EMBL:AFH03699.1};
DE EC=4.1.1.15 {ECO:0000313|EMBL:AAF53337.1, ECO:0000313|EMBL:AFH03699.1};
DE SubName: Full=Black, isoform B {ECO:0000313|EMBL:AFH03699.1};
DE SubName: Full=Glutamate decarboxylase {ECO:0000313|EMBL:AAC46466.1};
DE SubName: Full=LP11089p {ECO:0000313|EMBL:AAL39897.1};
GN Name=Adc {ECO:0000313|FlyBase:FBgn0000153};
GN Synonyms=ADC {ECO:0000313|EMBL:AAF53337.1}, anon-34Db
GN {ECO:0000313|EMBL:AAF53337.1}, B {ECO:0000313|EMBL:AAF53337.1}, b
GN {ECO:0000313|FlyBase:FBgn0000153}, BG:DS00941.5
GN {ECO:0000313|EMBL:AAF53337.1}, Black {ECO:0000313|EMBL:AAF53337.1},
GN cDNA 1 {ECO:0000313|EMBL:AAF53337.1}, DGad2
GN {ECO:0000313|EMBL:AAF53337.1}, Dmel\CG7811
GN {ECO:0000313|EMBL:AAF53337.1}, DmGad2 {ECO:0000313|EMBL:AAF53337.1},
GN Gad2 {ECO:0000313|EMBL:AAF53337.1}, GAD[[2]]
GN {ECO:0000313|EMBL:AAF53337.1};
GN ORFNames=CG7811 {ECO:0000313|EMBL:AAF53337.1,
GN ECO:0000313|FlyBase:FBgn0000153}, Dmel_CG7811
GN {ECO:0000313|EMBL:AAF53337.1};
OS Drosophila melanogaster (Fruit fly).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota;
OC Neoptera; Endopterygota; Diptera; Brachycera; Muscomorpha; Ephydroidea;
OC Drosophilidae; Drosophila; Sophophora.
OX NCBI_TaxID=7227 {ECO:0000313|EMBL:AAC46466.1};
RN [1] {ECO:0000313|EMBL:AAC46466.1}
RP NUCLEOTIDE SEQUENCE.
RC STRAIN=Oregon-R {ECO:0000313|EMBL:AAC46466.1};
RC TISSUE=Neural {ECO:0000313|EMBL:AAC46466.1};
RX PubMed=8376987; DOI=10.1111/j.1471-4159.1993.tb13621.x;
RA Phillips A.M., Salkoff L.B., Kelly L.E.;
RT "A neural gene from Drosophila melanogaster with homology to vertebrate and
RT invertebrate glutamate decarboxylases.";
RL J. Neurochem. 61:1291-1301(1993).
RN [2] {ECO:0000313|EMBL:AAC46466.1}
RP NUCLEOTIDE SEQUENCE.
RC STRAIN=Oregon-R {ECO:0000313|EMBL:AAC46466.1};
RC TISSUE=Neural {ECO:0000313|EMBL:AAC46466.1};
RA Phillips M.A.;
RL Submitted (SEP-1993) to the EMBL/GenBank/DDBJ databases.
RN [3] {ECO:0000313|EMBL:AAF53337.1, ECO:0000313|Proteomes:UP000000803}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Berkeley {ECO:0000313|Proteomes:UP000000803};
RX PubMed=10731132; DOI=10.1126/science.287.5461.2185;
RA Adams M.D., Celniker S.E., Holt R.A., Evans C.A., Gocayne J.D.,
RA Amanatides P.G., Scherer S.E., Li P.W., Hoskins R.A., Galle R.F.,
RA George R.A., Lewis S.E., Richards S., Ashburner M., Henderson S.N.,
RA Sutton G.G., Wortman J.R., Yandell M.D., Zhang Q., Chen L.X., Brandon R.C.,
RA Rogers Y.H., Blazej R.G., Champe M., Pfeiffer B.D., Wan K.H., Doyle C.,
RA Baxter E.G., Helt G., Nelson C.R., Gabor G.L., Abril J.F., Agbayani A.,
RA An H.J., Andrews-Pfannkoch C., Baldwin D., Ballew R.M., Basu A.,
RA Baxendale J., Bayraktaroglu L., Beasley E.M., Beeson K.Y., Benos P.V.,
RA Berman B.P., Bhandari D., Bolshakov S., Borkova D., Botchan M.R., Bouck J.,
RA Brokstein P., Brottier P., Burtis K.C., Busam D.A., Butler H., Cadieu E.,
RA Center A., Chandra I., Cherry J.M., Cawley S., Dahlke C., Davenport L.B.,
RA Davies P., de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I.,
RA Dietz S.M., Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C.,
RA Dunn P., Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S.,
RA Fleischmann W., Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M.,
RA Glasser K., Glodek A., Gong F., Gorrell J.H., Gu Z., Guan P., Harris M.,
RA Harris N.L., Harvey D., Heiman T.J., Hernandez J.R., Houck J., Hostin D.,
RA Houston K.A., Howland T.J., Wei M.H., Ibegwam C., Jalali M., Kalush F.,
RA Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A., Kimmel B.E., Kodira C.D.,
RA Kraft C., Kravitz S., Kulp D., Lai Z., Lasko P., Lei Y., Levitsky A.A.,
RA Li J., Li Z., Liang Y., Lin X., Liu X., Mattei B., McIntosh T.C.,
RA McLeod M.P., McPherson D., Merkulov G., Milshina N.V., Mobarry C.,
RA Morris J., Moshrefi A., Mount S.M., Moy M., Murphy B., Murphy L.,
RA Muzny D.M., Nelson D.L., Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R.,
RA Pacleb J.M., Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V.,
RA Reese M.G., Reinert K., Remington K., Saunders R.D., Scheeler F., Shen H.,
RA Shue B.C., Siden-Kiamos I., Simpson M., Skupski M.P., Smith T., Spier E.,
RA Spradling A.C., Stapleton M., Strong R., Sun E., Svirskas R., Tector C.,
RA Turner R., Venter E., Wang A.H., Wang X., Wang Z.Y., Wassarman D.A.,
RA Weinstock G.M., Weissenbach J., Williams S.M., WoodageT, Worley K.C.,
RA Wu D., Yang S., Yao Q.A., Ye J., Yeh R.F., Zaveri J.S., Zhan M., Zhang G.,
RA Zhao Q., Zheng L., Zheng X.H., Zhong F.N., Zhong W., Zhou X., Zhu S.,
RA Zhu X., Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M., Venter J.C.;
RT "The genome sequence of Drosophila melanogaster.";
RL Science 287:2185-2195(2000).
RN [4] {ECO:0000313|EMBL:AAL39897.1}
RP NUCLEOTIDE SEQUENCE.
RC STRAIN=Berkeley {ECO:0000313|EMBL:AAL39897.1};
RA Stapleton M., Brokstein P., Hong L., Agbayani A., Carlson J., Champe M.,
RA Chavez C., Dorsett V., Farfan D., Frise E., George R., Gonzalez M.,
RA Guarin H., Li P., Liao G., Miranda A., Mungall C.J., Nunoo J., Pacleb J.,
RA Paragas V., Park S., Phouanenavong S., Wan K., Yu C., Lewis S.E.,
RA Rubin G.M., Celniker S.;
RL Submitted (DEC-2001) to the EMBL/GenBank/DDBJ databases.
RN [5] {ECO:0000313|Proteomes:UP000000803}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Berkeley {ECO:0000313|Proteomes:UP000000803};
RX PubMed=12537568;
RA Celniker S.E., Wheeler D.A., Kronmiller B., Carlson J.W., Halpern A.,
RA Patel S., Adams M., Champe M., Dugan S.P., Frise E., Hodgson A.,
RA George R.A., Hoskins R.A., Laverty T., Muzny D.M., Nelson C.R.,
RA Pacleb J.M., Park S., Pfeiffer B.D., Richards S., Sodergren E.J.,
RA Svirskas R., Tabor P.E., Wan K., Stapleton M., Sutton G.G., Venter C.,
RA Weinstock G., Scherer S.E., Myers E.W., Gibbs R.A., Rubin G.M.;
RT "Finishing a whole-genome shotgun: release 3 of the Drosophila melanogaster
RT euchromatic genome sequence.";
RL Genome Biol. 3:RESEARCH0079-RESEARCH0079(2002).
RN [6] {ECO:0000313|Proteomes:UP000000803}
RP GENOME REANNOTATION.
RC STRAIN=Berkeley {ECO:0000313|Proteomes:UP000000803};
RX PubMed=12537572; DOI=10.1186/gb-2002-3-12-research0083;
RA Misra S., Crosby M.A., Mungall C.J., Matthews B.B., Campbell K.S.,
RA Hradecky P., Huang Y., Kaminker J.S., Millburn G.H., Prochnik S.E.,
RA Smith C.D., Tupy J.L., Whitfield E.J., Bayraktaroglu L., Berman B.P.,
RA Bettencourt B.R., Celniker S.E., de Grey A.D.N.J., Drysdale R.A.,
RA Harris N.L., Richter J., Russo S., Schroeder A.J., Shu S.Q., Stapleton M.,
RA Yamada C., Ashburner M., Gelbart W.M., Rubin G.M., Lewis S.E.;
RT "Annotation of the Drosophila melanogaster euchromatic genome: a systematic
RT review.";
RL Genome Biol. 3:RESEARCH0083.1-RESEARCH0083.22(2002).
RN [7] {ECO:0000313|Proteomes:UP000000803}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Berkeley {ECO:0000313|Proteomes:UP000000803};
RX PubMed=12537573;
RA Kaminker J.S., Bergman C.M., Kronmiller B., Carlson J., Svirskas R.,
RA Patel S., Frise E., Wheeler D.A., Lewis S.E., Rubin G.M., Ashburner M.,
RA Celniker S.E.;
RT "The transposable elements of the Drosophila melanogaster euchromatin: a
RT genomics perspective.";
RL Genome Biol. 3:RESEARCH0084.1-RESEARCH0084.20(2002).
RN [8] {ECO:0000313|EMBL:AAF53337.1, ECO:0000313|Proteomes:UP000000803}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Berkeley {ECO:0000313|Proteomes:UP000000803};
RX PubMed=12537574;
RA Hoskins R.A., Smith C.D., Carlson J.W., Carvalho A.B., Halpern A.,
RA Kaminker J.S., Kennedy C., Mungall C.J., Sullivan B.A., Sutton G.G.,
RA Yasuhara J.C., Wakimoto B.T., Myers E.W., Celniker S.E., Rubin G.M.,
RA Karpen G.H.;
RT "Heterochromatic sequences in a Drosophila whole-genome shotgun assembly.";
RL Genome Biol. 3:RESEARCH0085-RESEARCH0085(2002).
RN [9] {ECO:0000313|EMBL:AAF53337.1, ECO:0000313|Proteomes:UP000000803}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Berkeley {ECO:0000313|Proteomes:UP000000803};
RX PubMed=16110336; DOI=10.1371/journal.pcbi.0010022;
RA Quesneville H., Bergman C.M., Andrieu O., Autard D., Nouaud D.,
RA Ashburner M., Anxolabehere D.;
RT "Combined evidence annotation of transposable elements in genome
RT sequences.";
RL PLoS Comput. Biol. 1:166-175(2005).
RN [10] {ECO:0000313|EMBL:AAF53337.1}
RP NUCLEOTIDE SEQUENCE.
RA Celniker S., Carlson J., Wan K., Frise E., Hoskins R., Park S.,
RA Svirskas R., Rubin G.;
RL Submitted (AUG-2006) to the EMBL/GenBank/DDBJ databases.
RN [11] {ECO:0000313|EMBL:AAF53337.1, ECO:0000313|Proteomes:UP000000803}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Berkeley {ECO:0000313|Proteomes:UP000000803};
RX PubMed=17569856; DOI=10.1126/science.1139815;
RA Smith C.D., Shu S., Mungall C.J., Karpen G.H.;
RT "The Release 5.1 annotation of Drosophila melanogaster heterochromatin.";
RL Science 316:1586-1591(2007).
RN [12] {ECO:0000313|EMBL:AAF53337.1, ECO:0000313|Proteomes:UP000000803}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Berkeley {ECO:0000313|Proteomes:UP000000803};
RX PubMed=17569867; DOI=10.1126/science.1139816;
RA Hoskins R.A., Carlson J.W., Kennedy C., Acevedo D., Evans-Holm M.,
RA Frise E., Wan K.H., Park S., Mendez-Lago M., Rossi F., Villasante A.,
RA Dimitri P., Karpen G.H., Celniker S.E.;
RT "Sequence finishing and mapping of Drosophila melanogaster
RT heterochromatin.";
RL Science 316:1625-1628(2007).
RN [13] {ECO:0000313|EMBL:AAF53337.1}
RP NUCLEOTIDE SEQUENCE.
RX PubMed=26109357; DOI=.1534/g3.115.018929;
RG FlyBase Consortium;
RA Matthews B.B., Dos Santos G., Crosby M.A., Emmert D.B., St Pierre S.E.,
RA Gramates L.S., Zhou P., Schroeder A.J., Falls K., Strelets V., Russo S.M.,
RA Gelbart W.M., null;
RT "Gene Model Annotations for Drosophila melanogaster: Impact of High-
RT Throughput Data.";
RL G3 (Bethesda) 5:1721-1736(2015).
RN [14] {ECO:0000313|EMBL:AAF53337.1}
RP NUCLEOTIDE SEQUENCE.
RX PubMed=26109356; DOI=.1534/g3.115.018937;
RG FlyBase Consortium;
RA Crosby M.A., Gramates L.S., Dos Santos G., Matthews B.B., St Pierre S.E.,
RA Zhou P., Schroeder A.J., Falls K., Emmert D.B., Russo S.M., Gelbart W.M.,
RA null;
RT "Gene Model Annotations for Drosophila melanogaster: The Rule-Benders.";
RL G3 (Bethesda) 5:1737-1749(2015).
RN [15] {ECO:0000313|EMBL:AAF53337.1}
RP NUCLEOTIDE SEQUENCE.
RX PubMed=25589440;
RA Hoskins R.A., Carlson J.W., Wan K.H., Park S., Mendez I., Galle S.E.,
RA Booth B.W., Pfeiffer B.D., George R.A., Svirskas R., Krzywinski M.,
RA Schein J., Accardo M.C., Damia E., Messina G., Mendez-Lago M.,
RA de Pablos B., Demakova O.V., Andreyeva E.N., Boldyreva L.V., Marra M.,
RA Carvalho A.B., Dimitri P., Villasante A., Zhimulev I.F., Rubin G.M.,
RA Karpen G.H., Celniker S.E.;
RT "The Release 6 reference sequence of the Drosophila melanogaster genome.";
RL Genome Res. 25:445-458(2015).
Query Match 100.0%; Score 3024; Length 575;
Best Local Similarity 100.0%;
Matches 575; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 MLASENFPTHHFKESIFKPYSTTSGDDLASVSPLTATAALVASTSSPADSTSTVAFEQAS 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 MLASENFPTHHFKESIFKPYSTTSGDDLASVSPLTATAALVASTSSPADSTSTVAFEQAS 60
Qy 61 KMLANAANNNNNNNNNITSTKDDLSSFVASHPAAEFEGFIRACVDEIIKLAVFQGTNRSS 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 KMLANAANNNNNNNNNITSTKDDLSSFVASHPAAEFEGFIRACVDEIIKLAVFQGTNRSS 120
Qy 121 KVVEWHEPAELRQLFDFQLREQGESQDKLRELLRETIRFSVKTGHPYFINQLYSGVDPYA 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 KVVEWHEPAELRQLFDFQLREQGESQDKLRELLRETIRFSVKTGHPYFINQLYSGVDPYA 180
Qy 181 LVGQWLTDALNPSVYTYEVAPLFTLMEEQVLAEMRRIVGFPNGGQGDGIFCPGGSIANGY 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 LVGQWLTDALNPSVYTYEVAPLFTLMEEQVLAEMRRIVGFPNGGQGDGIFCPGGSIANGY 240
Qy 241 AISCARYRHSPESKKNGLFNAKPLIIFTSEDAHYSVEKLAMFMGFGSDHVRKIATNEVGK 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 AISCARYRHSPESKKNGLFNAKPLIIFTSEDAHYSVEKLAMFMGFGSDHVRKIATNEVGK 300
Qy 301 MRLSDLEKQVKLCLENGWQPLMVSATAGTTVLGAFDDLAGISEVCKKYNMWMHVDAAWGG 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 MRLSDLEKQVKLCLENGWQPLMVSATAGTTVLGAFDDLAGISEVCKKYNMWMHVDAAWGG 360
Qy 361 GALMSKKYRHLLNGIERADSVTWNPHKLLAASQQCSTFLTRHQQVLAQCHSTNATYLFQK 420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 361 GALMSKKYRHLLNGIERADSVTWNPHKLLAASQQCSTFLTRHQQVLAQCHSTNATYLFQK 420
Qy 421 DKFYDTSFDTGDKHIQCGRRADVFKFWFMWKAKGTQGLEAHVEKVFRMAEFFTAKVRERP 480
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 421 DKFYDTSFDTGDKHIQCGRRADVFKFWFMWKAKGTQGLEAHVEKVFRMAEFFTAKVRERP 480
Qy 481 GFELVLESPECTNISFWYVPPGLREMERNREFYDRLHKVAPKVKEGMIKKGSMMITYQPL 540
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 481 GFELVLESPECTNISFWYVPPGLREMERNREFYDRLHKVAPKVKEGMIKKGSMMITYQPL 540
Qy 541 RQLPNFFRLVLQNSCLEESDMVYFLDEIESLAQNL 575
|||||||||||||||||||||||||||||||||||
Db 541 RQLPNFFRLVLQNSCLEESDMVYFLDEIESLAQNL 575
Query = SEQ ID NO:29
Sbjct = GenBank accession No. AHN54424 (identical to GenBank accession No. NP_001285910)
NW Score Identities Positives Gaps
772 199/518(38%) 208/518(40%) 31/518(5%)
Query 1 SLPXXXXHXX---------------------------FXXXXXXXXLXXAXFXXTXRXNX 33
L + F + A F T R +
Sbjct 1 MLANAANNNNNNNNNITSTKDDLSSFVASHPAAEFEGFIRACVDEIIKLAVFQGTNRSSK 60
Query 34 VXXXXXPXXLXXXXXXXXXXXXXXXXXLXXXXXXXXXXSVKTGHPXFXNQLFSXXDXYXX 93
V P L L SVKTGHP F NQL+S D Y
Sbjct 61 VVEWHEPAELRQLFDFQLREQGESQDKLRELLRETIRFSVKTGHPYFINQLYSGVDPYAL 120
Query 94 XXQXXXDALNPXVYTXEVSPXFXLMEEXVLXEMRXXVGXXXXXXGDXXFXPGGSXXNGYX 153
Q DALNP VYT EV+P F LMEE VL EMR VG GD F PGGS NGY
Sbjct 121 VGQWLTDALNPSVYTYEVAPLFTLMEEQVLAEMRRIVGFPNGGQGDGIFCPGGSIANGYA 180
Query 154 ISCXRXXXXPXXKXKGLXXXPRLVXFTSXDXHYSXXKXXSXXGXGXDNVYXXXXXXXGXX 213
ISC R P K GL L+ FTS D HYS K G G D+V G
Sbjct 181 ISCARYRHSPESKKNGLFNAKPLIIFTSEDAHYSVEKLAMFMGFGSDHVRKIATNEVGKM 240
Query 214 XXXXLXXXXXRXXXEGXAXPFXVXATXGTTVXGAFDPXXXXAXXCXKXXXWXHXDAAWGG 273
L + E P V AT GTTV GAFD + C K W H DAAWGG
Sbjct 241 RLSDLEKQV-KLCLENGWQPLMVSATAGTTVLGAFDDLAGISEVCKKYNMWMHVDAAWGG 299
Query 274 GXXXSXKXXXLXXGXERXDSVTWNPHKXLXXPQQCSTXLXRXXXXLXXXXSXXAXYLFQK 333
G S K L G ER DSVTWNPHK L QQCST L R L S A YLFQK
Sbjct 300 GALMSKKYRHLLNGIERADSVTWNPHKLLAASQQCSTFLTRHQQVLAQCHSTNATYLFQK 359
Query 334 DKXYDTXXDXGDKHIQCGRRXDVXKFWXMWXAKGXXGXXXHXXXXFXXXXXXXXXXXXXX 393
DK YDT D GDKHIQCGRR DV KFW MW AKG G H F
Sbjct 360 DKFYDTSFDTGDKHIQCGRRADVFKFWFMWKAKGTQGLEAHVEKVFRMAEFFTAKVRERP 419
Query 394 XFXXVXXXPEXTNXCFWYXPXXXXXXXXXXXXXXXXXHXXAPXXKEXMXXXGXMMXTYQX 453
F V PE TN FWY P H AP KE M G MM TYQ
Sbjct 420 GFELVLESPECTNISFWYVPPGLREMERNREFYDRL-HKVAPKVKEGMIKKGSMMITYQP 478
Query 454 XXXXPNFFRXVXQXSXXXXXDMXXXXXXXEXXXXXLXX 491
PNFFR V Q S DM E L
Sbjct 479 LRQLPNFFRLVLQNSCLEESDMVYFLDEIESLAQNL-- 514
Query = SEQ ID NO:29
Sbjct = Genbank accession No. AFH03699
NW Score Identities Positives Gaps
709 199/579(34%) 207/579(35%) 92/579(15%)
Query 1 SLPXXXX----------------------------------------------------- 7
L
Sbjct 1 MLASENFPTHHFKESIFKPYSTTSGDDLASVSPLTATAALVASTSSPADSTSTVAFEQAS 60
Query 8 -----------------------------------HXXFXXXXXXXXLXXAXFXXTXRXN 32
F + A F T R +
Sbjct 61 KMLANAANNNNNNNNNITSTKDDLSSFVASHPAAEFEGFIRACVDEIIKLAVFQGTNRSS 120
Query 33 XVXXXXXPXXLXXXXXXXXXXXXXXXXXLXXXXXXXXXXSVKTGHPXFXNQLFSXXDXYX 92
V P L L SVKTGHP F NQL+S D Y
Sbjct 121 KVVEWHEPAELRQLFDFQLREQGESQDKLRELLRETIRFSVKTGHPYFINQLYSGVDPYA 180
Query 93 XXXQXXXDALNPXVYTXEVSPXFXLMEEXVLXEMRXXVGXXXXXXGDXXFXPGGSXXNGY 152
Q DALNP VYT EV+P F LMEE VL EMR VG GD F PGGS NGY
Sbjct 181 LVGQWLTDALNPSVYTYEVAPLFTLMEEQVLAEMRRIVGFPNGGQGDGIFCPGGSIANGY 240
Query 153 XISCXRXXXXPXXKXKGLXXXPRLVXFTSXDXHYSXXKXXSXXGXGXDNVYXXXXXXXGX 212
ISC R P K GL L+ FTS D HYS K G G D+V G
Sbjct 241 AISCARYRHSPESKKNGLFNAKPLIIFTSEDAHYSVEKLAMFMGFGSDHVRKIATNEVGK 300
Query 213 XXXXXLXXXXXRXXXEGXAXPFXVXATXGTTVXGAFDPXXXXAXXCXKXXXWXHXDAAWG 272
L + E P V AT GTTV GAFD + C K W H DAAWG
Sbjct 301 MRLSDLEKQV-KLCLENGWQPLMVSATAGTTVLGAFDDLAGISEVCKKYNMWMHVDAAWG 359
Query 273 GGXXXSXKXXXLXXGXERXDSVTWNPHKXLXXPQQCSTXLXRXXXXLXXXXSXXAXYLFQ 332
GG S K L G ER DSVTWNPHK L QQCST L R L S A YLFQ
Sbjct 360 GGALMSKKYRHLLNGIERADSVTWNPHKLLAASQQCSTFLTRHQQVLAQCHSTNATYLFQ 419
Query 333 KDKXYDTXXDXGDKHIQCGRRXDVXKFWXMWXAKGXXGXXXHXXXXFXXXXXXXXXXXXX 392
KDK YDT D GDKHIQCGRR DV KFW MW AKG G H F
Sbjct 420 KDKFYDTSFDTGDKHIQCGRRADVFKFWFMWKAKGTQGLEAHVEKVFRMAEFFTAKVRER 479
Query 393 XXFXXVXXXPEXTNXCFWYXPXXXXXXXXXXXXXXXXXHXXAPXXKEXMXXXGXMMXTYQ 452
F V PE TN FWY P H AP KE M G MM TYQ
Sbjct 480 PGFELVLESPECTNISFWYVPPGLREMERNREFYDRL-HKVAPKVKEGMIKKGSMMITYQ 538
Query 453 XXXXXPNFFRXVXQXSXXXXXDMXXXXXXXEXXXXXLXX 491
PNFFR V Q S DM E L
Sbjct 539 PLRQLPNFFRLVLQNSCLEESDMVYFLDEIESLAQNL-- 575
Conclusion
No claim is in condition for allowance.
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Any inquiry concerning this communication or earlier communications from the examiner should be directed to DELIA M RAMIREZ, Ph.D., whose telephone number is (571) 272-0938. The examiner can normally be reached on Monday-Friday from 8:30 AM to 5:00 PM. If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Robert B. Mondesi, can be reached at (408) 918-7584. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
/DELIA M RAMIREZ/Primary Examiner, Art Unit 1652
DR
March 5, 2026