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 .
Claims 1-9, 17, 20, and 25-30 are pending.
Election/Restrictions
Applicant’s election without traverse of the invention of Group I, drawn to promoters for expressing a transgene in a CD3+ cell, in the reply filed on 02 October 2025 is acknowledged.
Applicant’s election of the species SEQ ID NO 13 (ICOS) in the reply filed on 02 October 2025 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Claims 25-30 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 02 October 2025.
Claims 1-9, 17, and 20 are examined.
Information Disclosure Statement
The IDS has been considered.
The Spec. cites references.
The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
Drawings
The drawings are objected to because of the following informalities:
Text in the following figs. is fuzzy/low resolution and hard to read:
Fig. 1—text along x-axis,
Fig. 3B—most of the text on/in each chart.
Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code on p. 5, last full ¶. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
The use of the following terms, which are trade names or marks used in commerce, has been noted in this application in the §Examples:
PEIPro®
PolyPlus®
HYDROSORT (should be HYDROSART®)
Dynabeads™
Attune™
Alexa Fluor® (AF)
Brilliant Violet™ (BV)
Zombie NIR™
FICOLL®
Gibco™
CellFix™
PE/Dazzle™
NOTE: Applicant is responsible for identifying and fixing any and all such instances for the terms listed above and any other terms that are trade names or trademarks. The terms should be accompanied by the generic terminology; furthermore the terms should be capitalized wherever it/they appear(s) or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
Claim Interpretation
Claims that recite a promoter sequence for use are interpreted as reciting an intended use that does not affect the structure of the claimed promoter sequence. Therefore an intended use provides no patentable weight.
CD+ cells are understood to be any kind of cell that expresses CD3 including all Tcells because all Tcells are known to express CD3. See Wikipedia (“CD3 [immunology”. Available at en.wikipedia.org/wiki/CD3_(immunology). Accessed on 21 October 2025).
The Spec. does not define a transgene. A transgene is interpreted in its broadest reasonable sense: any gene that has been transferred from one organism to another. One organism is interpreted to be one individual organism.
The Spec. does not define a vector. A vector is interpreted in its broadest reasonable sense: an agent that allows for gene transfer. That interpretation is in part based on the fact that the Spec. clarifies (p. 1 L20-25) that viral vectors are just one exemplary kind of vector.
Claim Objections
Claim 6 recites …wherein the promoter is capable of expressing the transgene at a higher level… but for clarity should recite …wherein the promoter expresses the transgene at a higher level….
Claim 20 recites …wherein the [NP] is capable of delivery of the vector into a CD3+ cell but for clarity should recite …wherein the [NP] is capable of delivering the vector into a CD3+ cell or …wherein the [NP] is delivers the vector into a CD3+ cell.
Claim Rejections - 35 USC § 112
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 1-9, 17, and 20 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 applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention. This is a written description rejection.
Claims 1-4 (and claims depending therefrom) recite a promoter sequence for use in expression of a transgene under control of the promoter sequence in a CD3+ cell, the promoter sequence comprising nucleotides 1501-2000, 1001-2000, or 501-2000 of any of SEQ ID NOs: 2 or 13, or SEQ ID NOs 2 or 13, or a variant thereof having at least 90% identity to said sequence.
Those broad claims encompass the large genus and sub-genera of sequences that have at least 90% identity to SEQ ID NOs 2 or 13 or to nucleotides 1501-2000, 1001-2000, or 501-2000 of any of SEQ ID NOs: 2 or 13. Any nucleic acid sequence having at least 90% identity to SEQ ID NOs 2 or 13 or any of the portions thereof (i.e., nucleotides 1501-2000, 1001-2000, or 501-2000 of any of SEQ ID NOs: 2 or 13) would be encompassed by the claims as instantly presented. Claims 1-4 recite the large genus/subgenera of promoter sequences and variants that are used to express any transgene.
Claim 8 recites a promoter sequence for use in expression of a transgene under control of the promoter sequence. Claims 1-4 and 8 recite encompass the huge genus of transgenes that can be used with the promoter sequences.
Claim 6 recites that the promoter is capable of expressing the transgene at a higher level in CD3+ cells compare to CD3- cells. Claim 6 recites a genus of items identified solely by their function: the promoter is capable of expressing the transgene at a higher level in CD3+ cells compare to CD3- cells.
Claims 9 and 17 recite a nucleic acid molecule comprising the promoter sequences of Claim 1 and a cell comprising the nucleic acid molecule of Claim 9. Those broad claims encompass the large genus of nucleic acid molecules comprising the promoter sequences of Claim 1. Any nucleic acid molecule comprising the promoter sequences of Claim 1 (including having at least 90% identity to SEQ ID NOs 2 or 13) would be encompassed by the claims as instantly presented.
Claim 20 recites a nanoparticle (NP) comprising the vector of Claim 9 wherein the NP is capable of delivery of the vector into a CD3+ cell. The broad claim encompasses the large genus of NP that are capable of delivery of the vector. Claim 20 recites a genus of items identified solely by their function: the NP is capable of delivery of the vector into a CD3+ cell.
An original claim may lack written description support when a broad genus claim is presented but the disclosure only describes a narrow species with no evidence that the genus is contemplated. See Ariad Pharms., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1349-50 (Fed. Cir. 2010) (en banc). The written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, reduction to drawings, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus. See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406. See MPEP 2163.
Regarding Claims 1-4, sequences that have at least 90% identity to either SEQ ID NOs 2/13 or to nucleotides 1501-2000, 1001-2000, or 501-2000 of any of SEQ ID NOs: 2 or 13 encompasses a large genus of nt sequences that may be ≤10% different from SEQ ID NOs 2/13. A nt sequence could be or have:
up to 10% of the nts removed from SEQ ID NOs 2/13,
a single chunk comprising ≤10% of the nts different from SEQ ID NOs 2/13,
every 10th nt (starting at any position) different from SEQ ID NOs 2/13,
every 10th nt (starting at any position) removed from SEQ ID NOs 2/13,
any other combination of nts mutated or removed from SEQ ID NOs 2/13 as long as the total adds up to ≤10% of total nts.
Each of those categories comprises a broad subgenus with diverse members and different structures that affect their functions. Since SEQ ID NOs 2/13 are each 2000 nt, that means as many as 200 nt could be altered or absent or added to SEQ ID NOs 2/13. Some of those sequence structures may have altered promoter activity or other altered function(s) (e.g., when it comes to expressing a transgene). For example, Smale (and Kadonaga. 2003. The RNA Polymerase II Core Promoter. Annu. Rev. Biochem. 72:449-479, “Smale”) teaches (§PROPERTIES OF RNA POLYMERASE II CORE PROMOTER ELEMENTS) core elements that are required for transcription. 10% alteration to the claimed SEQ ID NOs 2 or 13 or truncated sequences could result in those necessary elements being lost. At the same time, Wikipedia (“Promoter (genetics)”. Available online at en.wikipedia.org. Accessed on 22 October 2025, “Wikipedia”) teaches (§Eukaryotic) there is no such thing as a set of “universal elements” found in every core promoter. Since the required elements can vary, an adequate written description describing those elements is required to substantiate the full scope of the claims was in Applicant’s possession at time of filing.
Aside from disclosing (starting at p. 23) SEQ ID NOs 2/13 themselves, the Spec. does not provide any guidance on what portions of SEQ ID NOs 2/13 may or may not be altered. Regarding what structure is encompassed by the sequences that have at least 90% identity to either SEQ ID NOs 2/13 or to nucleotides 1501-2000, 1001-2000, or 501-2000 of any of SEQ ID NOs: 2 or 13, the Spec. does not provide information describing requisite features. The Spec. does not disclose what physical structure(s) are required for their invention. Furthermore, the claims recite the intended use of expressing a transgene. But the Spec. does not disclose what structures may or may not be altered or how any alterations may or may not affect transgene expression.
Regarding the transgene of Claim 1 and claims depending therefrom and Claim 8, the Spec. discloses (p. 6 full ¶1) the transgene can be any gene. The Spec. discloses that (same §) such transgenes can be intended for immunotherapy involving enhancing the activity of a T-cell or a sub-population of T-cells, including CD4+ cells, CD8+ cells, Th cells, or Treg cells. The following ¶ discloses still more potential transgenes:
an anti-checkpoint protein or polypeptide, such as an inhibitor of CTLA-4, PD1, POL 1, LAG-3, TIM 3, B7-H3, ICOS, IDO, 4-1 BB, or CD47… a chimeric antigen receptor (CAR) having binding specificity for any desired antigen, such as a tumor antigen or an antigen on the surface of a pathogen such as a bacterium, virus, yeast, or parasite. The CAR can be a universal CAR, which binds to an adapter molecule having a domain for CAR binding as well as an antigen binding domain suitable for binding to an antigen such as a tumor antigen or an antigen on the surface of a pathogen such as a bacterium, virus, yeast, or parasite. The transgene can be a protein or a combination of proteins able to elicit an immune response and act as a vaccine. The elicited immune response can be prophylactic or therapeutic, and can stimulate an immune response against bacteria, viruses, other microbial pathogens, or cancer cells, or another undesired cell type found in the body of a subject
That encompasses a huge number of potential transgenes—literally any gene in existence. But Applicant’s Spec. and Examples do not demonstrate possession of the promoter sequence used with any transgene or with a representative number of transgenes from the huge genus of all transgenes. The Examples disclose using the exact sequences encoded by each SEQ ID NO and the two transgenes (pp. 7-8, 11; Table 2) GFP and CAR-CD19. The Examples do not disclose any other transgenes.
Applicant’s examples show possession of the claimed SEQ ID NOs 2/13 and portions of them (i.e., nucleotides 1501-2000, 1001-2000, or 501-2000 of any of SEQ ID NOs: 2 or 13), but not sequences having 90% identity to those sequences. Those examples are not sufficient to provide written description support for sequences having 90% identity to the claimed sequences.
Although the Specification teaches the examples discussed above, it does not identify a core structure or nucleotide sequence (or way to identify such a sequence) of which at least 90% must be preserved and which is common among various members of the claimed genus. No core structure, partial structure, physical or chemical property, or functional characteristic coupled with a known or disclosed structure/function relationship of a promoter sequence comprising a sequence having at least 90% identity to nts 1501-2000, 1001-2000, or 501-2000 of SEQ ID NOs 2/13, or a sequence having at least 90% identity to SEQ ID NOs 2/13 is disclosed in such a way to demonstrate possession of the full invention as claimed at time of filing.
The specification teaches only these species within the claimed genus/genera: SEQ ID NOs 2 and 13 themselves. But those are only a paltry number compared with the breadth of what is claimed. Altogether, the number of species disclosed by complete structure is not sufficient to provide the written description support for the huge genera and subgenera that are encompassed by the claims: a promoter sequence comprising a sequence having at least 90% identity to nts 1501-2000, 1001-2000, or 501-2000 of SEQ ID NOs 2/13, or a sequence having at least 90% identity to SEQ ID NOs 2/13.
Regarding the transgenes recited in Claims 1 and 8, the Spec. discloses only GFP and CAR-CD19. The Spec. has not, therefore, demonstrated possession of the full invention as claimed (i.e., comprising any transgene) at time of filing.
Regarding Claim 6, the Spec. discloses (starts on p. 5, final ¶) the promoter sequence is capable of selectively promoting expression of a transgene in CD3+ cells compared to CD3- cells. However, the Spec. does not disclose what structure(s) makes the promoter capable of expressing the transgene at a higher level in CD3+ cells compared to CD3- cells.
Claim 6 recites a functional characteristics (i.e., the promoter sequence is capable of selectively promoting expression of a transgene in CD3+ cells compared to CD3- cells), but the functional characteristic is not coupled with any known structure. An artisan therefore would not know whether or not the promoter having a truncated sequence or having at least 90% identity to the claimed SEQ ID NOs is capable of expressing the transgene at a higher level in a CD3+ cell compared to a CD3- cell.
The Spec. does not identify a core structure necessary for performing the claimed function(s) of selectively promoting expression of a transgene in CD3+ cells compared to CD3- cells. The Spec. does not disclose any core structure, partial structure, physical or chemical property, or functional characteristic coupled with a known or disclosed structure/function relationship responsible for selectively promoting expression of a transgene in CD3+ cells compared to CD3- cells in such a way to demonstrate possession of the full invention as claimed at time of filing.
Regarding Claims 9 and 17, the Spec. does not disclose any nucleic acid molecules that comprise the promoter sequence of Claim 1 aside from SEQ ID NOs 2 and 13 themselves.
Although Claims 9 and 17 recite the huge genera of nucleic acid molecules comprising the promoter sequence of Claim 1, they have not demonstrated possession of the full invention as claimed at time of filing.
Regarding Claim 20, the Spec. does not disclose what structure makes the NP capable of delivery of the vector into a CD3+ cell. Although Claim 20 recites a functional characteristics (i.e., wherein the NP is capable of delivery of the vector into a CD3+ cell), the functional characteristic is not coupled with any known structure. The Examples teach that (p. 22) NP comprising “bald” lentiviral vectors (LV) resulted in no expression of GFP, and they describe that nanoparticles comprising poly(beta-amino ester)s (PBAEs) restored their transduction efficiency. That indicates that the NP comprising PBAE were capable of delivery of the vector into a CD3+ cell. However, the Spec. has described no core structure responsible for the claimed function. An artisan therefore would not know whether a NP is or is not capable of delivering the vector into a CD3+ cell.
Although the Specification teaches the examples discussed above, it does not identify a core structure necessary for performing the claimed function(s) of delivering the vector into a CD3+ cell. The Spec. does not disclose any core structure, partial structure, physical or chemical property, or functional characteristic coupled with a known or disclosed structure/function relationship responsible for delivering the vector into a CD3+ cell in such a way to demonstrate possession of the full invention as claimed at time of filing.
The specification teaches only these species within the claimed genus/genera: PBAEs. But those are only a paltry number compared with the breadth of what is claimed. Altogether, the Spec. has not described what makes a NP capable or not capable of delivering a vector into a CD3+ cell. The number of species of things that make a NP capable of delivering a vector into a CD3+ cell disclosed by complete structure is not sufficient to provide the written description support for the huge genera encompassed by the claims.
Altogether, the Spec. does not disclose: what structures must be preserved from SEQ ID NOs 2/13, the structure that makes the promoter capable of expressing the transgene at a higher level in CD3+ cells compared to CD3- cells, or the structure that makes a NP capable of delivering the vector into a CD3+ cell. The Spec. has not disclosed a representative number of transgenes or nucleic acid molecules comprising the promoter.
While none of these elements is specifically required to demonstrate possession, in combination their absence means that one skilled in the art at the time of filing would conclude that the inventors lacked possession of the full breadth of the invention claimed. Claims 1-4, 6, 8-9, and 20 are rejected for failing to demonstrate possession of the claimed invention. Claims 2-7, 9, 17, and 20 are rejected because they depend from Claim(s) 1-3 and/or 9 and do not remedy the issues.
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.
Section 33(a) of the America Invents Act reads as follows:
Notwithstanding any other provision of law, no patent may issue on a claim directed to or encompassing a human organism.
Claim 17 is rejected under 35 U.S.C. 101 and section 33(a) of the America Invents Act as being directed to or encompassing a human organism. See also Animals - Patentability, 1077 Off. Gaz. Pat. Office 24 (April 21, 1987) (indicating that human organisms are excluded from the scope of patentable subject matter under 35 U.S.C. 101).
Claim 17 recites a cell comprising the vector, plasmid, or nucleic acid molecule of Claim 9 and therefore could be interpreted to read on a human organism. Amending the claim to recite the following, as appropriate, would obviate the rejection:
An isolated cell comprising the vector, plasmid, or nucleic acid molecule of Claim 9.
Claims 1-9, 17, and 20 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a product of nature without significantly more.
The claim(s) recite(s) a promoter sequence for use in expression of a transgene under control of a promoter sequence in a CD3+ cell, the promoter sequence comprising nucleotides 1501-2000, 1001-2000, or 501-2000 of SEQ ID NOs 2 or 13, or a variant having at least 90% identity to any of those sequences, or comprising SEQ ID NO 2 (Claims 1-4, 8); wherein the promoter sequence comprises a binding sequence for one or more transcription factors selected from the group consisting of… (Claim 5); wherein the promoter is capable of expressing the transgene at a higher level in CD3+ cells compared to CD3- cells (Claim 6); wherein the ratio of expression in CD3+ cells to CD3- cells is at least 2:1 (Claim 7); a… nucleic acid molecule comprising the promoter sequence of Claim 1 (Claim 9); a cell comprising the nucleic acid molecule of Claim 9 (Claim 17); and a nanoparticle comprising the vector of Claim 9, wherein the nanoparticle is capable of delivery of the vector into a CD3+ cell (Claim 20).
This judicial exception is not integrated into a practical application because the recited sequences exist in cells in Nature. The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the sequences exist within cells in Nature.
Claims 1-4 and 8 recite a promoter sequence for use in expression of a transgene under control of a promoter sequence in a CD3+ cell, the promoter sequence comprising nucleotides 1501-2000, 1001-2000, or 501-2000 of SEQ ID NOs 2 or 13, or a variant having at least 90% identity to any of those sequences, or comprising SEQ ID NO 2.
Claim 5 recites that the promoter comprises binding sequences for a number of transcription factors.
Claims 6 and 7 recite that the promoter expresses the transgene at a higher level in CD3+ cells vs CD3- cells, including at a ratio of 2:1 higher expression in CD3+ cells.
Claim 9 recites a vector/plasmid/nucleic acid molecule comprising the promoter sequence; Claim 17 recites a cell comprising a vector/plasmid/nucleic acid molecule comprising the promoter sequence; and Claim 20 recites a nanoparticle comprising the promoter sequence.
The claimed characteristics are not markedly different from the product’s naturally occurring counterpart in the natural state. This judicial exception is not integrated into a practical application because the claims do not provide a promoter that is markedly different from its naturally occurring counterpart (Claims 1-9 and 17) or a promoter that is markedly different from something routine and conventional (Claim 20).
Step 1 – Statutory Category: The claimed invention is either a composition of matter or a manufacture. Under 35 USC 101, the claimed invention must be “any new and useful process, machine, manufacture, or composition of matter.” The composition comprising SEQ ID NO 2 or comprising portions of SEQ ID NO 13 can be considered a composition of matter or a manufactured product. Therefore, the composition falls under one of the statutory categories identified in 35 USC 101.
Step 2A Judicial Exception – Prong 1 (Nature of the claim recitation & Markedly different characteristics analysis): Prong 1 asks whether the claim recites an abstract idea, law of nature, or natural phenomenon (product of nature). Even a composition or a manufactured product may not be patent-eligible if it falls under a judicial exception. Nature-based products falling within the judicial exception can include 1) naturally occurring products or 2) those that are not naturally occurring but have characteristics that are not markedly different from a naturally occurring counterpart. The Federal Circuit in University of Utah Research Foundation v. Ambry Genetics (Fed. Circ. December 2014) held claimed synthetically made primers that have the identical nucleotide sequences as portions (i.e., fragments) of naturally occurring nucleic acids are ineligible nature-based products. The court reasoned that simply being synthetic or non-naturally created is not enough for eligibility when the identical sequences occur in nature.
The instantly claimed invention is a composition but recites the promoter comprises SEQ ID NO 2. The following sequence alignment demonstrates that SEQ ID NO 2 is found within the human genome:.
RESULT 1
AC008746
LOCUS AC008746 200070 bp DNA linear PRI 17-JAN-2003
DEFINITION Homo sapiens chromosome 19 clone CTD-2587H19, complete sequence.
ACCESSION AC008746
VERSION AC008746.10
KEYWORDS HTG.
SOURCE Homo sapiens (human)
ORGANISM Homo sapiens
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
Catarrhini; Hominidae; Homo.
REFERENCE 1 (bases 1 to 200070)
AUTHORS DOE Joint Genome Institute and Stanford Human Genome Center.
TITLE Direct Submission
JOURNAL Unpublished
REFERENCE 2 (bases 1 to 200070)
AUTHORS DOE Joint Genome Institute.
TITLE Direct Submission
JOURNAL Submitted (03-AUG-1999) Production Sequencing Facility, DOE Joint
Genome Institute, 2800 Mitchell Drive, Walnut Creek, CA 94598, USA
REFERENCE 3 (bases 1 to 200070)
AUTHORS DOE Joint Genome Institute and Stanford Human Genome Center.
TITLE Direct Submission
JOURNAL Submitted (01-AUG-2002) DOE Joint Genome Institute, 2800 Mitchell
Drive, Walnut Creek, CA 94598, USA
REFERENCE 4 (bases 1 to 200070)
AUTHORS DOE Joint Genome Institute and Stanford Human Genome Center.
TITLE Direct Submission
JOURNAL Submitted (17-JAN-2003) DOE Joint Genome Institute, 2800 Mitchell
Drive, Walnut Creek, CA 94598, USA
COMMENT On Jan 17, 2003 this sequence version replaced AC008746.9.
Draft Sequence Produced by DOE Joint Genome Institute
www.jgi.doe.gov
Finishing Completed at Stanford Human Genome Center
www-shgc.stanford.edu
Quality: Phrap Quality >=40 99.9\% of Sequence;
Estimated Total Number of Errors is 0.1.
NOTE: Forced join 88769
NOTE: Shatter libraries failed to resolve dinucleotide repeat
region 83591-83893. Unsure number of repeat copies 83591-83893.
Forced Join 83797.
FEATURES Location/Qualifiers
source 1..200070
/organism="Homo sapiens"
/mol_type="genomic DNA"
/db_xref="taxon:9606"
/chromosome="19"
/clone="CTD-2587H19"
misc_feature 82591..83893
/note="NOTE: Forced join 88769
NOTE: Shatter libraries failed to resolve dinucleotide
repeat region 83591-83893. Unsure number of repeat copies
83591-83893. Forced Join 83797.
Query Match 100.0%; Score 2000; Length 200070;
Best Local Similarity 100.0%;
Matches 2000; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 CCCACTTGCTCCCTGGGCTTGGAGCACAACCACTCAAACAGAACTGGCTTTTGGTCAGTA 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 175526 CCCACTTGCTCCCTGGGCTTGGAGCACAACCACTCAAACAGAACTGGCTTTTGGTCAGTA 175585
Qy 61 AGGAAGAAGTGAGCAACGGCTGCGGTGTAGACCCTCGTCAATGCCTGCGACGGTTACACC 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 175586 AGGAAGAAGTGAGCAACGGCTGCGGTGTAGACCCTCGTCAATGCCTGCGACGGTTACACC 175645
Qy 121 TGGAGACAAGCTCCCCAGTGTCCTCAGGAGCAGCGGAGATGAGAATCCATGATAGGGTGG 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 175646 TGGAGACAAGCTCCCCAGTGTCCTCAGGAGCAGCGGAGATGAGAATCCATGATAGGGTGG 175705
Qy 181 GCTCTGTCCCCCTCAGCTCCGTGATGCCGAAATGCACTGCTGGTCCTGGTCCTGCTCCTC 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 175706 GCTCTGTCCCCCTCAGCTCCGTGATGCCGAAATGCACTGCTGGTCCTGGTCCTGCTCCTC 175765
Qy 241 ATTCCACACCCGGCTGAGTGCCCATCTGACCCCAGACCTCAACGCGAGGTTCTAAGCACT 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 175766 ATTCCACACCCGGCTGAGTGCCCATCTGACCCCAGACCTCAACGCGAGGTTCTAAGCACT 175825
Qy 301 GTCTCCTGACCCTTCAACCCCTTCGGGATTTTGCATGTGCTGTTGGACCACCTCACTCCC 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 175826 GTCTCCTGACCCTTCAACCCCTTCGGGATTTTGCATGTGCTGTTGGACCACCTCACTCCC 175885
Qy 361 ACCTGGAGCCAAATGACACTGTAGGAGGAGGGGAAGAGAACTTATGCTAGTAGAGTGTGT 420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 175886 ACCTGGAGCCAAATGACACTGTAGGAGGAGGGGAAGAGAACTTATGCTAGTAGAGTGTGT 175945
Qy 421 GTGTGTGTGTGTGTGTGTGTGTGAATGTGTGTGTGTATTATACATAATATATATAATTAC 480
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 175946 GTGTGTGTGTGTGTGTGTGTGTGAATGTGTGTGTGTATTATACATAATATATATAATTAC 176005
Qy 481 AACATTGTTAATGGGGCCGGGCGCGGTGGCTCACACCTGTAATCACAGCACTTTGGGAGG 540
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 176006 AACATTGTTAATGGGGCCGGGCGCGGTGGCTCACACCTGTAATCACAGCACTTTGGGAGG 176065
Qy 541 CTGAGATGGGCAGATCACATGAGGTCAGGAGTTCAAGACCAGCCTGGCCAACATGGTGAA 600
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 176066 CTGAGATGGGCAGATCACATGAGGTCAGGAGTTCAAGACCAGCCTGGCCAACATGGTGAA 176125
Qy 601 ACCCCGTCTCTACTAAAATACAAAAATTAGCCGGGCATGGTGGCGTGCGCCTGTAGTCCC 660
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 176126 ACCCCGTCTCTACTAAAATACAAAAATTAGCCGGGCATGGTGGCGTGCGCCTGTAGTCCC 176185
Qy 661 GGCTACTCAGCAGGCTGAGGCAAGAGAATTGCTTGAGCCTGGGAGGCGGAGGTTGCAGTG 720
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 176186 GGCTACTCAGCAGGCTGAGGCAAGAGAATTGCTTGAGCCTGGGAGGCGGAGGTTGCAGTG 176245
Qy 721 AGCCAAGATTGCACCACTGCACTCCAGCCTGGGCAACAGAGTACGACTCCATCTCCACAC 780
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 176246 AGCCAAGATTGCACCACTGCACTCCAGCCTGGGCAACAGAGTACGACTCCATCTCCACAC 176305
Qy 781 ACACATACACACACACACACACACACACAAATTGTTAATTGTATATGTATAATTATAATA 840
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 176306 ACACATACACACACACACACACACACACAAATTGTTAATTGTATATGTATAATTATAATA 176365
Qy 841 GTTTATATATATTAACAATTATATATAAACTTGCATATATATAGTATTTGCTGTATTATT 900
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 176366 GTTTATATATATTAACAATTATATATAAACTTGCATATATATAGTATTTGCTGTATTATT 176425
Qy 901 ATATATAAACAATTATATATGTAATGACTGTATAAAATAGATAAACAATTTTAACTAATA 960
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 176426 ATATATAAACAATTATATATGTAATGACTGTATAAAATAGATAAACAATTTTAACTAATA 176485
Qy 961 ATATTATATTAATTATATTATTATTAGATGTAATAATTATAATTATTTATATATAATATT 1020
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 176486 ATATTATATTAATTATATTATTATTAGATGTAATAATTATAATTATTTATATATAATATT 176545
Qy 1021 TATTATTATGTATCATTGTTAGAACACTTAACGTGAGCTCTGTCCTCTTAACAAATTTCA 1080
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 176546 TATTATTATGTATCATTGTTAGAACACTTAACGTGAGCTCTGTCCTCTTAACAAATTTCA 176605
Qy 1081 AGTGAACAAGACGTTATTGCTGACGATGGGTCGTATGTGGTGCAGCAGATCTCTAGGCCT 1140
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 176606 AGTGAACAAGACGTTATTGCTGACGATGGGTCGTATGTGGTGCAGCAGATCTCTAGGCCT 176665
Qy 1141 GTTTGTTAATAACTCCCCATTTCCCCCTCCTCCCAGCCCCCGTAACCACCATTCCCTGCT 1200
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 176666 GTTTGTTAATAACTCCCCATTTCCCCCTCCTCCCAGCCCCCGTAACCACCATTCCCTGCT 176725
Qy 1201 GTGATGTTGTGACTCTGGTGACTTTGCAGATCTCCTGTAAGTGACATCATGCAGTACTTG 1260
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 176726 GTGATGTTGTGACTCTGGTGACTTTGCAGATCTCCTGTAAGTGACATCATGCAGTACTTG 176785
Qy 1261 GTCTCTGCCTCTGCGTCGCTTGGCGTGATGTCCTCAGGTTTCGTCCGTGTTGTCGCCCAT 1320
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 176786 GTCTCTGCCTCTGCGTCGCTTGGCGTGATGTCCTCAGGTTTCGTCCGTGTTGTCGCCCAT 176845
Qy 1321 GGCAGAATTTTCTTCCTTGTTTAAGGCTGAATAGTATTCCCCTGTGTGTGCACCACATTT 1380
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 176846 GGCAGAATTTTCTTCCTTGTTTAAGGCTGAATAGTATTCCCCTGTGTGTGCACCACATTT 176905
Qy 1381 TCTATATCAATTCTTCTATCAATGGACATTTAGATGATTTTCACGTCTTAGCTATTGCGA 1440
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 176906 TCTATATCAATTCTTCTATCAATGGACATTTAGATGATTTTCACGTCTTAGCTATTGCGA 176965
Qy 1441 ATAGTGCTGCAGTGATCAGGGGAGTTCAGACGGCTCTTTGCATACTGAATTTGTTTCTTT 1500
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 176966 ATAGTGCTGCAGTGATCAGGGGAGTTCAGACGGCTCTTTGCATACTGAATTTGTTTCTTT 177025
Qy 1501 TAAATATAGACCCAGAAGTGGCATTGTTGGACCATACGGTAGCTCTATGTTTAGTTTTTT 1560
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 177026 TAAATATAGACCCAGAAGTGGCATTGTTGGACCATACGGTAGCTCTATGTTTAGTTTTTT 177085
Qy 1561 GAGGAACCTCCCCACTGTTCTCTATAGTGAGTGCACAATTTTTCAGCCTCCCAAAGTGCT 1620
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 177086 GAGGAACCTCCCCACTGTTCTCTATAGTGAGTGCACAATTTTTCAGCCTCCCAAAGTGCT 177145
Qy 1621 GGGATCACAGGCGTGAGCCACCGCGCCCGGCGCACTGTAGGATCTTTTTTAATGCATTAT 1680
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 177146 GGGATCACAGGCGTGAGCCACCGCGCCCGGCGCACTGTAGGATCTTTTTTAATGCATTAT 177205
Qy 1681 ATACCTTGCTGAGATTTTAGCAGAGATCACAATATTAAAAACTTGGGGAAGGATTTCTAT 1740
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 177206 ATACCTTGCTGAGATTTTAGCAGAGATCACAATATTAAAAACTTGGGGAAGGATTTCTAT 177265
Qy 1741 GACTCTCATTTTAAATACAAGGACATGTCGACTTCTAGTTTTGTAACATCTTGCCCAAGA 1800
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 177266 GACTCTCATTTTAAATACAAGGACATGTCGACTTCTAGTTTTGTAACATCTTGCCCAAGA 177325
Qy 1801 GCGGTGGTCGTTAATGTGTGGAGTTGGGATGACATCCAAGTCAGTTGGTTGCACGACCTT 1860
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 177326 GCGGTGGTCGTTAATGTGTGGAGTTGGGATGACATCCAAGTCAGTTGGTTGCACGACCTT 177385
Qy 1861 TATTCTGTCTTGTCCCATAGATTTAGAAAGAGGCTGACACATCGGGTAACTAGTTTAAGG 1920
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 177386 TATTCTGTCTTGTCCCATAGATTTAGAAAGAGGCTGACACATCGGGTAACTAGTTTAAGG 177445
Qy 1921 TCATCTGATCATGCGGGTAAGCGACATTTTTCAGAAACCAAGGCCCTCCCTCTCATCTCA 1980
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 177446 TCATCTGATCATGCGGGTAAGCGACATTTTTCAGAAACCAAGGCCCTCCCTCTCATCTCA 177505
Qy 1981 CTAGTGGGAAGGGTGGAAAG 2000
||||||||||||||||||||
Db 177506 CTAGTGGGAAGGGTGGAAAG 177525
In addition, data provided by The Human Protein Atlas (“Lair2” and [see following ¶s] “ICOS”. Available at proteinatlas.org. Accessed on 21 October 2025, “Atlas”) shows that Lair2 (which an artisan would understand is under the control of its own promoter sequence in a natural setting) is expressed in CD3+ cells, including at a ratio of at least 2:1 (see, e.g., data for §Immune Cell Type Expression [RNA]). Portions of those data are presented here:
PNG
media_image1.png
394
1178
media_image1.png
Greyscale
Similarly, the claims recite the promoter comprises a variant having at least 90% identity to nt SEQ ID NO 13. The following sequence alignment demonstrates that recited sequence is found within the human genome:
RESULT 2
AJ535718/c
LOCUS AJ535718 186585 bp DNA linear PRI 08-NOV-2003
DEFINITION Homo sapiens partial ICOS gene for inducible costimulator protein.
ACCESSION AJ535718
VERSION AJ535718.1
KEYWORDS ICOS gene; inducible costimulator protein.
SOURCE Homo sapiens (human)
ORGANISM Homo sapiens
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
Catarrhini; Hominidae; Homo.
REFERENCE 1
AUTHORS Ueda,H., Howson,J., Heward,J., Esposito,L., Snook,H., Smith,A.,
DiGenova,G., Herr,M., Dahlman,I., Payne,F., Smyth,D., Lowe,C.,
Twells,R., Howlett,S., Healy,B., Smink,L., Lam,A., Cordell,H.J.,
Walker,N., Hulme,J., Bordin,C., Cucca,F., Motzo,C., Hess,F.,
Metzker,M., Chamberlain,G., Rainbow,D., Hunter,K., Rogers,J.,
Gregory,S., Allahabadia,A., Nithiyananthan,R., Tuomilehto,J.,
Tuomilehto Wolf,E., Bingley,P., Gillespie,K., Undlien,D.,
Ronningen,K., Savage,D., Franklyn,J.A., Clayton,D., Peterson,L.B.,
Wicker,L.S., Todd,J.A. and Gough,S.C.
TITLE Increased levels of alternative isoforms of the T
lymphocyte-inhibitory receptor, cytotoxic T lymphocyte antigen-4,
are associated with genetic protection from autoimmune disease
JOURNAL Unpublished
REFERENCE 2 (bases 1 to 186585)
AUTHORS Todd,J.A.
TITLE Direct Submission
JOURNAL Submitted (08-NOV-2002) Todd J.A., JDRF/WT DIL, Cambridge Institute
for Medical Research, Hills Road, Cambridge, CB2 2XY, UNITED
KINGDOM
FEATURES Location/Qualifiers
source 1..186585
/organism="Homo sapiens"
/mol_type="genomic DNA"
/db_xref="taxon:9606"
/chromosome="2"
/map="2q33"
/clone="278L16"
/clone_lib="RPCI-11"
gene complement(11552..91402)
/gene="ICOS"
CDS complement(join(11552..11566,13269..13352,14386..14492,
15180..15515,91345..91402))
/gene="ICOS"
/codon_start=1
/product="inducible costimulator protein"
/protein_id="CAD59742.1"
/db_xref="GDB:10450295"
/db_xref="GOA:Q9Y6W8"
/db_xref="HGNC:HGNC:5351"
/db_xref="InterPro:IPR013783"
/db_xref="UniProtKB/Swiss-Prot:Q9Y6W8"
/translation="MKSGLWYFFLFCLRIKVLTGEINGSANYEMFIFHNGGVQILCKY
PDIVQQFKMQLLKGGQILCDLTKTKGSGNTVSIKSLKFCHSQLSNNSVSFFLYNLDHS
HANYYFCNLSIFDPPPFKVTLTGGYLHIYESQLCCQLKFWLPIGCAAFVVVCILGCIL
ICWLTKKKYSSSVHDPNGEYMFMRAVNTAKKSRLTDVTL"
exon complement(11552..11566)
/gene="ICOS"
intron complement(11567..13268)
/gene="ICOS"
exon complement(13269..13352)
/gene="ICOS"
intron complement(13353..14385)
/gene="ICOS"
exon complement(14386..14492)
/gene="ICOS"
intron complement(14493..15179)
/gene="ICOS"
exon complement(15180..15515)
/gene="ICOS"
intron complement(15516..91344)
/gene="ICOS"
exon complement(91345..91402)
/gene="ICOS
Query Match 99.9%; Score 1999; Length 186585;
Best Local Similarity 100.0%;
Matches 1999; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 2 TAATTTCTAGCCAAATAAATGAGGATAAGTGTGTGAGTGTGGTGGGGTAGTTAAGAGTTT 61
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 93484 TAATTTCTAGCCAAATAAATGAGGATAAGTGTGTGAGTGTGGTGGGGTAGTTAAGAGTTT 93425
Qy 62 GGAATCCAGAGTTTCACTGTCTGGATTTGAACAGGCTCCGTTGCTCATCAGCTCTGTGAC 121
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 93424 GGAATCCAGAGTTTCACTGTCTGGATTTGAACAGGCTCCGTTGCTCATCAGCTCTGTGAC 93365
Qy 122 TCCGGGCAAATGACTGAATCTCTCTAACTCTCAGTTTTCTCATCTATGAAATGAGAATAA 181
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 93364 TCCGGGCAAATGACTGAATCTCTCTAACTCTCAGTTTTCTCATCTATGAAATGAGAATAA 93305
Qy 182 GTAACAGACTCTCCCTCGCTGAGTTGTTTGAGAACGGGATCAGACAATGCACGTGGAGCC 241
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 93304 GTAACAGACTCTCCCTCGCTGAGTTGTTTGAGAACGGGATCAGACAATGCACGTGGAGCC 93245
Qy 242 CCGTGTCTGGCACACACTATGTCCTCATTGCATATTTATTATTAGGTTTCTGCTTTGTAT 301
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 93244 CCGTGTCTGGCACACACTATGTCCTCATTGCATATTTATTATTAGGTTTCTGCTTTGTAT 93185
Qy 302 TTTTCTCTGTGCAACAGCCCTGAGCTCTAGAACTTATGACAGCTTTTCTCAAGTGAAGTT 361
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 93184 TTTTCTCTGTGCAACAGCCCTGAGCTCTAGAACTTATGACAGCTTTTCTCAAGTGAAGTT 93125
Qy 362 AAAGTTCCCCATACTCAGTTCCAGAGCTAGGCCTCACCTAGGTTGGAAGAAGTCAATTGT 421
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 93124 AAAGTTCCCCATACTCAGTTCCAGAGCTAGGCCTCACCTAGGTTGGAAGAAGTCAATTGT 93065
Qy 422 TCTCCACTGCCTGCCTGTGTGCTGGGAAAGGACTCTAGCACAGTGCCGGTGGGGCTGGAA 481
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 93064 TCTCCACTGCCTGCCTGTGTGCTGGGAAAGGACTCTAGCACAGTGCCGGTGGGGCTGGAA 93005
Qy 482 GCCTTTCCTCATGATGCTACGGGGAGTACAGTGAAAAGGGAGGAGATTGGGGTAGCAAGG 541
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 93004 GCCTTTCCTCATGATGCTACGGGGAGTACAGTGAAAAGGGAGGAGATTGGGGTAGCAAGG 92945
Qy 542 TCCCAGGGGTCCTGGCAGCCCAGGCTCTACTTCTCAGGCTAGCTCAGTCCCTCAAACAGC 601
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 92944 TCCCAGGGGTCCTGGCAGCCCAGGCTCTACTTCTCAGGCTAGCTCAGTCCCTCAAACAGC 92885
Qy 602 TTCCTTCACACCCACTGCTGAGACCCAGGAGCCCTACAGAAGGTAGCTAGGGGAAGCTTC 661
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 92884 TTCCTTCACACCCACTGCTGAGACCCAGGAGCCCTACAGAAGGTAGCTAGGGGAAGCTTC 92825
Qy 662 AGCAGCTAGGGGGATCCCTGCAGGATCAGCCTCCTCCTTACCTTGCAGACCCCTTGGCTG 721
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 92824 AGCAGCTAGGGGGATCCCTGCAGGATCAGCCTCCTCCTTACCTTGCAGACCCCTTGGCTG 92765
Qy 722 TGGTCTGGCATTCCTAGTGGCTGGCCTAAAGCCCCAAACCTGGAATCTGTTTCAGAGCCT 781
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 92764 TGGTCTGGCATTCCTAGTGGCTGGCCTAAAGCCCCAAACCTGGAATCTGTTTCAGAGCCT 92705
Qy 782 GGACCTTTTGGACTCACACCTTGGTTTCCCTGGCCAGCTGATTTCAGCTTCTCATCTAAA 841
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 92704 GGACCTTTTGGACTCACACCTTGGTTTCCCTGGCCAGCTGATTTCAGCTTCTCATCTAAA 92645
Qy 842 TGTCATTTCTGCAGGCTAAGGGAAGTCCAGCCTGGATCTAGCATCTTGGAAGCGCGTTCA 901
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 92644 TGTCATTTCTGCAGGCTAAGGGAAGTCCAGCCTGGATCTAGCATCTTGGAAGCGCGTTCA 92585
Qy 902 GACTTCTGGATGGAGGGATCAGCAGGCCTTGGTATTGGTGGTTCTACCTGCTTCGGTTAA 961
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 92584 GACTTCTGGATGGAGGGATCAGCAGGCCTTGGTATTGGTGGTTCTACCTGCTTCGGTTAA 92525
Qy 962 GAGTGAGGACTCTGGAGCCAGACTCTCTAAATCATAGCACTGACACTTACTATATGACTT 1021
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 92524 GAGTGAGGACTCTGGAGCCAGACTCTCTAAATCATAGCACTGACACTTACTATATGACTT 92465
Qy 1022 GGGCCAGGTTCGTTACCTGTCTGTGCCTCAGTTTTCCTCATCTGTAAAATGGGAGATTAG 1081
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 92464 GGGCCAGGTTCGTTACCTGTCTGTGCCTCAGTTTTCCTCATCTGTAAAATGGGAGATTAG 92405
Qy 1082 TGGTCACCATTGGGATGATTAAGAAGATTAAATGAGTTAATGTATGTATAAACTATAGTT 1141
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 92404 TGGTCACCATTGGGATGATTAAGAAGATTAAATGAGTTAATGTATGTATAAACTATAGTT 92345
Qy 1142 ATAATGTAAATATATATACAAACAGTAACCATTTACATGCATATAAAACATAATATAAAT 1201
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 92344 ATAATGTAAATATATATACAAACAGTAACCATTTACATGCATATAAAACATAATATAAAT 92285
Qy 1202 GTAATATTAGCTATATTCATATATAAAAATAGGTATATTTTATATATAAAATATATTACA 1261
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 92284 GTAATATTAGCTATATTCATATATAAAAATAGGTATATTTTATATATAAAATATATTACA 92225
Qy 1262 TTTAATTTTTTACATTTTGCATTAAGATATATTATTTCATATAAAACATTTAAGTACATA 1321
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 92224 TTTAATTTTTTACATTTTGCATTAAGATATATTATTTCATATAAAACATTTAAGTACATA 92165
Qy 1322 TACATATAATTATCTATGTAATTATTATTGTTATTGTTGTTATTGTCTACTTTACCTCCC 1381
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 92164 TACATATAATTATCTATGTAATTATTATTGTTATTGTTGTTATTGTCTACTTTACCTCCC 92105
Qy 1382 TGCAGGGATGGGGAGACCACGGCAGGCTTTTAAACATTCTTGGTCTCACTGAGCCGTAGG 1441
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 92104 TGCAGGGATGGGGAGACCACGGCAGGCTTTTAAACATTCTTGGTCTCACTGAGCCGTAGG 92045
Qy 1442 TGAGGAATCCCTGGTTCCTACAGACTCTGCTGTAATATGAGGAGCAGGGTTTAAGTTAGT 1501
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 92044 TGAGGAATCCCTGGTTCCTACAGACTCTGCTGTAATATGAGGAGCAGGGTTTAAGTTAGT 91985
Qy 1502 TTAAAACTGACCCCATCATTTGAAACATTGCAATCTACAATGAATGCCACATAAATATCA 1561
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 91984 TTAAAACTGACCCCATCATTTGAAACATTGCAATCTACAATGAATGCCACATAAATATCA 91925
Qy 1562 TTTCTCAGATTCCTATGATGCTCTTCTTTCAGATCTTTTCACTTCAATTTCTATAATAAT 1621
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 91924 TTTCTCAGATTCCTATGATGCTCTTCTTTCAGATCTTTTCACTTCAATTTCTATAATAAT 91865
Qy 1622 TTTGTTTGTTTCTTGTCCTATTTCAAAGGCTTTCTTATCTCTGGAGCACCTAGCATAAGA 1681
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 91864 TTTGTTTGTTTCTTGTCCTATTTCAAAGGCTTTCTTATCTCTGGAGCACCTAGCATAAGA 91805
Qy 1682 TAGAAATGTGTCAAAATATATGTTTTATTCATCATGTGAGTATTTTTAGGTCCTGTTAAC 1741
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 91804 TAGAAATGTGTCAAAATATATGTTTTATTCATCATGTGAGTATTTTTAGGTCCTGTTAAC 91745
Qy 1742 CCCCATAACTATTGATTCAGAGAAGTAGGGTGGTTCTGAAAAATACAGGCATAATCTCTT 1801
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 91744 CCCCATAACTATTGATTCAGAGAAGTAGGGTGGTTCTGAAAAATACAGGCATAATCTCTT 91685
Qy 1802 TAACTTGTTTTATAGGAACCAGAATAAGGGTAATGTTTTCCTCTGTCTTCAAAATCATCA 1861
|||||||||||||||||||||||||||||||||||||||||||||