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 .
Claim Interpretation
The terms glucose-6-phosphatase-a and G6Pase-a are being interpreted as glucose-6-phosphatase-α and G6Pase-α.
Claim Objections
Claims 4, 7, and 19 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Status of Prior Rejections/Response to Arguments
RE: Rejection of claims 4, 6- 8, 10, and 15 under 35 U.S.C. 112(b)
Regarding claim 4: Applicants have amended claim 4 to define the term “optimized” and remove the term “preferably”. The amendments overcomes the rejection of record.
Regarding claims 6-8, 10, and 15: Applicants have amended claims 6-8, 10, and 15 to remove the terms/phrases “such as”, “preferably” and “e.g.”. The amendments overcome the rejections of record.
The rejections over claims 4, 6-8, 10, and 15 are withdrawn.
RE: Rejection of claims 1, 4-6, and 8-15 under 35 U.S.C. 102 over Alexander et al (WO2018129586A1) as evidenced by Genecards (G6PC1 page) and Chou (US10415044).
Applicants traversed the rejection of record on the grounds that Alexander et al only lists glucose-6-phosphatase in a long list of potential transgenes but does not use a glucose-6-phosphatase transgene in any examples.
In response, the argument has been fully considered but is not convincing. Alexander et al teaches, in particular embodiments the transgene is glucose-6-phosphatase and specifically claims a polynucleotide comprising a glucose-6-phosphatase in claim 21 (See ¶0012, 0057, and claim 21). A reference need not exemplify an embodiment to anticipate.
Applicants further traverse the rejection of record on the grounds that Alexander et al generically lists “glucose-6-phosphastase” but does not specify the G6Pase-a isoform. Applicant suggests the term “glucose-6-phosphatase” as used in Alexander could thus be interpreted as other isoforms of the catalytic subunit such as IGRP or glucose 6-phophaste-ß.
In response, the argument has been fully considered but the rejection cannot be withdrawn at this time. Genecards (G6PC1 page) teaches the G6PC1 gene is alternatively known as G6Pase-α and glucose-6-phosphatase whereas IGRP is alternatively known as Glucose-6-phosphatase 2 and Glucose 6-phophaste-ß is alternatively known as Glucose-6-phosphatase 3. Based on the evidence of record, the term “glucose-6-phophatase” as used in Alexander et al is interpreted as referring to G6Pase-α.
Applicants amendments to claim 4, requiring a G6Pase-a that is codon optimized by decreasing the content of GC and decreasing GC dimers overcomes the rejection of claim 4.
The rejection over claim 4 is withdrawn.
The rejection over claims 1, 5-6, and 8-15 is maintained.
RE: Rejection of claims 1-6 and 8-15 under 35 U.S.C. 103 over Alexander et al (WO2018129586A1) in view of Chou (US10415044B2).
Applicants traversed the rejection of record on the grounds that Alexander does not disclose G6Pase-a and thus the combination of Alexander and Chou amounts to impermissible hindsight.
In response to applicant's argument that the examiner's conclusion of obviousness is based upon improper hindsight reasoning, it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971). As discussed in the response to the 102 rejection over Alexander et al, Genecards teaches Glucose-6-phosphatase and G6Pase-α are both alternative names for G6PC1. Thus, substitution of one G6Pase-α for another G6Pase-α is not considered hindsight reasoning.
Applicants further traverse the rejection of record on the grounds that a person of ordinary skill in the art would not have replaced the hOTC enhancer of Alexander et al with an ApoE enhancer or cis-regulatory module because the hOTC enhancer is an essential element of the genetic construct described in Alexander et al.
In response, the argument has been fully considered but is not persuasive. None of the rejected claims require an ApoE enhancer or cis-regulatory element.
Additionally, applicants traverse the rejection of record on the grounds that a G6Pase-α under the control of the hAAT promoter reduces the risk of tumor formation as compared with the hGPE promoter in the context of gene therapy which is an unexpected result.
In response, the argument has been fully considered however Alexander teaches a Glucose-6-phosphatase under control of a hAAT promoter. Thus, the AAV of Alexander would produce the same results.
Applicants amendments to claim 4, requiring a G6Pase-a that is codon optimized by decreasing the content of GC and decreasing GC dimers. The codon optimized G6Pase-α of Chou et al has increased GC content compared to human G6Pase-α as well as compared to the modified human G6PC encoding 298C G6Pase-α. Thus amendments to claim 4 overcome the rejection.
The rejection over claim 4 is withdrawn.
The rejection over claims 1-3, 5-6 and 8-15 is maintained.
New/Maintained Rejections
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1, 5-6, and 8-15 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Alexander et al (WO2018129586A1) as evidenced by Genecards (G6PC1 page) and Chou (US10415044).
Alexander et al teaches a polynucleotide sequence comprising from 5’ to 3’ a human ornithine transcarbamylase (hOTC) enhancer, a liver specific promoter, and a transgene which is operably linked to the liver-specific promoter (See ¶007). In some embodiments, the polynucleotide further comprises an intron and/or a Kozak sequence between the promoter and the transgene and a polyadenylation signal 3’ of the transgene. Thus in some embodiments, the polynucleotide sequence comprises from 5’ to 3’ a hOTC enhancer, a liver-specific promoter, an intron, a Kozak sequence, a transgene and a polyadenylation signal (See ¶007 and Fig. 1). The transgene can include glucose-6-phosphatase (See ¶0012 and claim 21). The liver specific promoter can be a human alpha 1 antitrypsin (hAAT) promoter comprising SEQ ID NO: 4 (See ¶009 and claims 8 and 17). Alexander et al further teaches an AAV comprising the polynucleotide sequence (See claims 30 and 34). The AAV is usually of serotype AAV2, AAV3, or AAV8 but can comprise any of AAV1-AAV9 or any variants thereof (See ¶0082). The AAV can be used to express the transgene in liver cells and can be used as a treatment for a disease or disorder associated with the liver (See ¶006 and ¶0056). Additionally, the vector or polynucleotide can be part of a pharmaceutical composition which comprises the vector or polynucleotide and a pharmaceutically acceptable carrier (See ¶0088).
Regarding claim 1: Alexander et al teaches an AAV vector comprising a polynucleotide sequence comprising a glucose-6-phophatase transgene (reads on G6Pase-a (See Genecards)) which can be used to express the transgene in a liver cell. Thus the AAV vector of Alexander et al reads on an AAV vector comprising a nucleic acid construct for the expression of a glucose06-phosphatase-a (G6Pase-a) in a cell. The glucose-6-phosphastase transgene of Alexander et al is operably linked to a hAAT promoter which reads on the G6Pase-a is operably linked to a hAAT promoter.
Regarding claim 5: Following the discussion of claim 1 above, the polynucleotide sequence of Alexander et al comprises a hAAT promoter comprising an amino acid sequence of SEQ ID NO: 4. of Alexander et al is 100% identical to SEQ ID NO: 8 of the instant application (See sequence alignment at end of office action).
Regarding claim 6: Following the discussion of claim 1 above, the AAV of Alexander et al comprises a hOTC enhancer 5’ of the hAAT promoter which reads on the hAAT promoter is preceded by an enhancer.
Regarding claim 8: Following the discussion of claim 1 above, in some embodiments, the AAV vector of alexander comprises a polynucleotide sequence which comprises from 5’ to 3’ 3’ a hOTC enhancer, a hAAT promoter, an intron, a Kozak sequence, a glucose-6-phosphatase transgene, and a polyadenylation signal which reads on the nucleic acid construct comprise in the 5’ to 3’ orientation, a hAAT promoter preceded by an enhancer, a nucleic acid sequence encoding the G6Pase-a, and a polyadenylation signal.
Regarding claim 9: Following the discussion of claim 1 above, the AAV of Alexander et al (reads on the AAV of claim 1) is used to express a transgene in a liver cell.
Regarding claim 10: Following the discussion of claim 1 above, the AAV of Alexander et al (reads on the AAV of claim 1) is usually an AAV with a liver tropic serotype such as AAV8 which reads on the AAV is an AAV serotype 8.
Regarding claims 11 and 12: Alexander et al discloses using the an AAV (reads on the AAV of claim 1) to express a transgene in a liver cell. Thus, the liver cell in which the transgene is expressed reads on a cell transformed with the AAV vector of claim 1.
Regarding claim 13: Alexander et al discloses a pharmaceutical composition comprising the AAV (reads on the AAV of claim 1) vector and a pharmaceutically acceptable carrier.
Regarding claim 14: Alexander discloses the AAV (reads on the AAV of claim 1) can be used to express the transgene in liver cells and can be used as a treatment for a disease or disorder associated with the liver which reads on the AAV vector for use as a medicament.
Regarding claim 15: Alexander et al discloses an AAV which can be used to express Glucose-6-phosphatase in liver cells and can be used as a treatment for a liver disease. Chou teaches Glycogen storage disease type Ia (GSD-Ia) is caused by a deficiency in glucose-6-phosphatase, which is primarily expressed in the liver, kidney, and intestine (See Col. 1, lns 26-29). Given that GSD-Ia is caused by a deficiency of glucose-6-phosphatase in liver and Alexander et al teaches an AAV which can be used to express glucose-6-phosphatase in the liver, the liver disease treatment method of Alexander et al is inherently a method for treating GSD-Ia (reads on a glycogen storage disease) (See MPEP2112.02).
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
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 1-3, 5-6, and 8-15 are rejected under 35 U.S.C. 103 as being unpatentable over Alexander et al (WO2018129586A1), as evidenced by Genecards (G6PC1 page) , in view of Chou (US10415044B2).
The teachings of Alexander et al are set forth above.
Alexander et al anticipates claims 1, 5, 6, and 8-15.
Regarding claim 2: Following the discussion of claim 1 above, Alexander et al discloses the vector of claim 1 which can be used to treat a liver disease.
Alexander et al does not disclose the G6Pase-a has an amino acid sequence having at least 90% identity to SEQ ID NO: 1.
Chou discloses a nucleic acid molecule encoding a modified G6Pase-α (reads on G6Pase-a) comprising an amino acid sequence of SEQ ID NO: 8 (See claims 1-2). SEQ ID NO: 8 of Chou is 99.5% identical to SEQ ID NO: 1 of the instant application (See alignment at end of office action). Chou further discloses an AAV8 vector comprising the nucleic acid molecule (See claims 4, 9, and 10). The AAV vector can be used for gene therapy in treatment of glycogen storage disease type Ia (GSD-Ia).
Given that both Alexander et al and Chou teach AAV vectors expressing Glucose-6-phosphatase which can be used to treat a liver disease, it would be obvious to substitute the amino acid sequence encoding Glucose-6-phosphatase of Alexander et al with SEQ ID NO: 8 of Chou which encodes a modified G6Pase-α (reads on Glucose-6-phosphatase). One would have expected SEQ ID NO: 8 of Chou and the amino acid sequence encoding Glucose-6-phosphatase of Alexander et al to work equivocally, in the AAV of Alexander et al, because both sequences encode Glucose-6-phosphatase and in an AAV that can be used to treat a liver disease. Substitution of one element for another known in the field, wherein the result of the substitution would have been predictable is considered to be obvious. See KSR International Co. V Teleflex Inc 82 USPQ2d 1385 (US2007) at page 1395.
Regarding claim 3: Following the discussion of claim 1 above, Following the discussion of claim 1 above, Alexander et al discloses the vector of claim 1 which can be used to treat a liver disease.
Alexander et al does not disclose the G6Pase-a has a nucleic acid sequence having at least 90% identity to SEQ ID NO: 2.
Chou discloses a nucleic acid molecule encoding a modified G6Pase-α (reads on G6Pase-a) comprising a nucleotide sequence of SEQ ID NO: 6 (See claims 1 and 3). SEQ ID NO: 6 of Chou is 99.7% identical to SEQ ID NO: 1 of the instant application (See alignment at end of office action). Chou further discloses an AAV8 vector comprising the nucleic acid molecule (See claims 4, 9, and 10). The AAV vector can be used for gene therapy in treatment of glycogen storage disease type Ia (GSD-Ia).
Given that both Alexander et al and Chou teach AAV vectors expressing Glucose-6-phosphatase which can be used to treat a liver disease, it would be obvious to substitute the nucleotide sequence encoding Glucose-6-phosphatase of Alexander et al with SEQ ID NO: 6 of Chou which encodes a modified G6Pase-α (reads on Glucose-6-phosphatase). One would have expected SEQ ID NO: 6 of Chou and the nucleotide sequence encoding Glucose-6-phosphatase of Alexander et al to work equivocally, in the AAV of Alexander et al, because both sequences encode Glucose-6-phosphatase in an AAV that can be used to treat a liver disease. Substitution of one element for another known in the field, wherein the result of the substitution would have been predictable is considered to be obvious. See KSR International Co. V Teleflex Inc 82 USPQ2d 1385 (US2007) at page 1395.
Claims 1-3, 5-6, 8-18, and 20-22 are rejected under 35 U.S.C. 103 as being unpatentable over Chou (US10415044B2) in view of Von Maltzahn et al (WO2020014209A1) and as evidenced by Genecards (G6PC1 page).
Chou discloses an AAV8 vector comprising a nucleic acid molecule encoding a modified G6Pase-α (reads on G6Pase-a) comprising an amino acid sequence of SEQ ID NO: 8 (See pg. 2, lns 14-24 and claims 1, 2, 4, 9, and 10). The G6Pase-α is under the control of a promoter such as a G6Pase-α promoter and enhancer (See pg. 2, lns 18-20). The AAV vector can be used for gene therapy in treatment of glycogen storage disease type Ia (GSD-Ia) (See pg. 2 ln 31- pg. 3 ln 2). Chou teaches delivery of a G6Pase-α transgene to the liver an achieve extended correction of GSD-Ia (See pg. 11 ln 27-pg 12 ln, 2).
Regarding claims 1, 9-14, and 22: Chou discloses an AAV8 comprising a nucleic acid for the expression of G6Pase-α. The AAV of Chou can be used as a gene therapy for GSD-Ia which can be corrected by expressing G6Pase-α in the liver.
Chou does not disclose a G6Pase-α operably linked to a hAAT promoter.
Von Maltzahn et al discloses fusosomes, including retroviral vectors and lentiviral vectors for expression of a therapeutic transgene in liver cells (See pg. 2 lns 5-10). The fusosome comprises a payload gene operably linked to a liver specific promoter such as ApoE.HCR-hAAT promoter which includes an ApoE enhancer and hAAT promoter(See pg. 3, lns 25-29, Table 3, and claim 32). The therapeutic transgene can be G6PC (Reads on G6Pase-α) (See claim 21 and Genecards G6PC1 page).
Given that Chou teaches a vector for expressing G6Pase-α which can be used to treat GSD-Ia by expressing G6Pase-α in the liver and Von Maltzahn teaches an ApoE.HCR-hAAT promoter can be used to express G6Pase-α in the liver, it would have been prima facie obvious to modify the AAV of Chou to include an ApoE.HCR-hAAT promoter, in order to express G6Pase-α in liver cells (reads on a cell transformed with the vector of claim 1) as a treatment for GSD-Ia. One would have been motivated to modify the AAV of Chou by adding an ApoE.HCR-hAAT promoter because Chou teaches expressing G6Pase-α in the liver can correct GSD-Ia. There is a reasonable expectation of success because Von Maltzahn teaches an ApoE.HCR-hAAT promoter can be used to drive expression of G6Pase-α in the liver.
Regarding claim 2: Following the discussion of claim 1 above, Chou discloses a nucleic acid molecule encoding a modified G6Pase-α (reads on G6Pase-a) comprising an amino acid sequence of SEQ ID NO: 8 (See claims 1-2). SEQ ID NO: 8 of Chou is 99.5% identical to SEQ ID NO: 1 of the instant application (See alignment at end of office action).
Regarding claim 3: Following the discussion of claim 1 above, Chou discloses a nucleic acid molecule encoding a modified G6Pase-α (reads on G6Pase-a) comprising a nucleotide sequence of SEQ ID NO: 6 (See claims 1 and 3). SEQ ID NO: 6 of Chou is 99.7% identical to SEQ ID NO: 1 of the instant application (See alignment at end of office action).
Regarding claim 5: Following the discussion of claim 1 above, Chou discloses an AAV8 comprising a G6Pase-α which can be expressed in the liver to correct GSD-Ia. Von Maltzahn teaches an ApoE.HCR-hAAT promoter comprising SEQ ID NO. 133 (See table 3 and claim 32) which drives liver specific expression. It would have been obvious to modify the vector of Chou to comprise the ApoE.HCR-hAAT of Von Maltzahn in order to drive liver specific expression of G6Pase-α (See claim 1 rejection above). SEQ ID NO. 133 of Von Maltzahn is 100% identical to SEQ ID NO: 8 of the instant application (See sequence alignment at end of office action).
Regarding claim 6: Following the discussion of claim 1 above, Chou discloses an AAV8 comprising a G6Pase-α which can be expressed in the liver to correct GSD-Ia. Von Maltzahn teaches an ApoE.HCR-hAAT promoter comprising an ApoE enhancer preceding a hAAT to drive liver specific expression promoter (See table 3, SEQ ID NO:133, and claim 32). It would have been obvious to modify the vector of Chou to comprise the ApoE.HCR-hAAT of Von Maltzahn in order to drive liver specific expression of G6Pase-α (See claim 1 rejection above).
Regarding claim 8, 16, and 20-21: Following the discussion of claim 1 above, Chou discloses an AAV8 comprising a G6Pase-α which can be expressed in the liver to correct GSD-Ia. Von Maltzahn teaches an ApoE.HCR-hAAT promoter to drive liver specific expression (See table 3, SEQ ID NO:133, and claim 32). SEQ ID NO: 133 of Von Maltzahn comprises a region 100% identical to SEQ ID NO:9 of the instant application (See sequence alignment at end of office action). It would have been obvious to modify the vector of Chou to comprise the ApoE.HCR-hAAT of Von Maltzahn in order to drive liver specific expression of G6Pase-α (reads on a hAAT promoter preceded by an enhancer 5’ of a G6Pase-α encoding sequence) (See claim 1 rejection above).
Von Maltzahn further teaches including a polyadenylation signal sequence 3’ of a gene promotes mRNA stability leasing to increase translational efficiency (See pg. 50, lns 8-15). Therefore, it would have been obvious to further modify the vector of Chou in order to add a polyA sequence 3’ of G6Pase-α in order to improve stability of G6Pase-α mRNA. One would have been motivated to include a PolyA signal (reads on a naturally occurring or artificial polyadenylation signal) in the vector of Chou in order to improve to improve stability of G6Pase-α mRNA. There is a reasonable expectation of success because adding polyA signals 3’ of a gene to increase translational efficiency is a known technique in the art.
Regarding claim 15 and 23: Chou in view of Von Maltzahn teach an AAV for expression of G6Pase-α in the liver as a treatment for GSD-Ia (See rejection of claim 1 above) which reads on a method of treating glycogen storage disease comprising administering to a subject the AAV of claim 1.
Regarding claim 17: Following the discussion of claim 1 above, Chou discloses an AAV8 comprising a G6Pase-α which can be expressed in the liver to correct GSD-Ia. Von Maltzahn teaches an ApoE.HCR-hAAT promoter comprising SEQ ID NO. 133 (See table 3 and claim 32) which drives liver specific expression. It would have been obvious to modify the vector of Chou to comprise the ApoE.HCR-hAAT of Von Maltzahn in order to drive liver specific expression of G6Pase-α (See claim 1 rejection above). SEQ ID NO. 133 of Von Maltzahn is 100% identical to SEQ ID NO: 9 of the instant application (See sequence alignment at end of office action).
Regarding claim 18: Following the discussion of claim 1 above, Chou discloses an AAV8 comprising a G6Pase-α which can be expressed in the liver to correct GSD-Ia. Von Maltzahn teaches an ApoE.HCR-hAAT promoter comprising SEQ ID NO. 133 (See table 3 and claim 32) which drives liver specific expression. It would have been obvious to modify the vector of Chou to comprise the ApoE.HCR-hAAT of Von Maltzahn in order to drive liver specific expression of G6Pase-α (See claim 1 rejection above). SEQ ID NO. 133 of Von Maltzahn is 100% identical to SEQ ID NO: 7 of the instant application (See sequence alignment at end of office action).
Allowable Subject Matter
While all claims are rejected, the subject matter of claims 4, 7, and 19 would be allowable if written in independent form.
Regarding claim 4: Claim 4 has been amended to define a codon optimized G6Pase-a as a G6Pase-a with decreased GC content and decreased GC dimers. The codon optimized G6Pase-a of Chou comprises higher GC content compared to human G6Pase-α as well as compared to the modified human G6PC encoding 298C G6Pase-α.
Regarding claim 7: The closest prior art to claim 7 is SEQ ID NO: 22 from US11339406B2 which has 41.2% identity with SEQ ID NO: 55 of the instant application.
Regarding claim 19: The closes prior art to claim 19 is SEQ ID NO: 53 from US16332379 which has a 41.1% identity with SEQ ID NO: 48 of the instant application.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MARISOL A O'NEILL whose telephone number is (571)272-2490. The examiner can normally be reached Monday - Friday 7:30 - 5:00 EST.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Christopher Babic can be reached at (571) 272-8507. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/MARISOL ANN O'NEILL/Examiner, Art Unit 1633
/ALLISON M FOX/ Primary Examiner, Art Unit 1633
SEQUENCE ALIGNMENTS
QY (SEQ ID NO: 8) vs. DB (SEQ ID NO: 4 of Alexander et al)
Query Match 100.0%; Score 392; DB 1; Length 406;
Best Local Similarity 100.0%;
Matches 392; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 TGCTACCAGTGGAACAGCCACTAAGGATTCTGCAGTGAGAGCAGAGGGCCAGCTAAGTGG 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 15 TGCTACCAGTGGAACAGCCACTAAGGATTCTGCAGTGAGAGCAGAGGGCCAGCTAAGTGG 74
Qy 61 TACTCTCCCAGAGACTGTCTGACTCACGCCACCCCCTCCACCTTGGACACAGGACGCTGT 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 75 TACTCTCCCAGAGACTGTCTGACTCACGCCACCCCCTCCACCTTGGACACAGGACGCTGT 134
Qy 121 GGTTTCTGAGCCAGGTACAATGACTCCTTTCGGTAAGTGCAGTGGAAGCTGTACACTGCC 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 135 GGTTTCTGAGCCAGGTACAATGACTCCTTTCGGTAAGTGCAGTGGAAGCTGTACACTGCC 194
Qy 181 CAGGCAAAGCGTCCGGGCAGCGTAGGCGGGCGACTCAGATCCCAGCCAGTGGACTTAGCC 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 195 CAGGCAAAGCGTCCGGGCAGCGTAGGCGGGCGACTCAGATCCCAGCCAGTGGACTTAGCC 254
Qy 241 CCTGTTTGCTCCTCCGATAACTGGGGTGACCTTGGTTAATATTCACCAGCAGCCTCCCCC 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 255 CCTGTTTGCTCCTCCGATAACTGGGGTGACCTTGGTTAATATTCACCAGCAGCCTCCCCC 314
Qy 301 GTTGCCCCTCTGGATCCACTGCTTAAATACGGACGAGGACAGGGCCCTGTCTCCTCAGCT 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 315 GTTGCCCCTCTGGATCCACTGCTTAAATACGGACGAGGACAGGGCCCTGTCTCCTCAGCT 374
Qy 361 TCAGGCACCACCACTGACCTGGGACAGTGAAT 392
||||||||||||||||||||||||||||||||
Db 375 TCAGGCACCACCACTGACCTGGGACAGTGAAT 406
QY (SEQ ID NO: 1) vs. DB (SEQ ID NO: 8 of Chou)
Query Match 99.5%; Score 1893; DB 1; Length 357;
Best Local Similarity 99.7%;
Matches 356; Conservative 0; Mismatches 1; Indels 0; Gaps 0;
Qy 1 MEEGMNVLHDFGIQSTHYLQVNYQDSQDWFILVSVIADLRNAFYVLFPIWFHLQEAVGIK 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 MEEGMNVLHDFGIQSTHYLQVNYQDSQDWFILVSVIADLRNAFYVLFPIWFHLQEAVGIK 60
Qy 61 LLWVAVIGDWLNLVFKWILFGQRPYWWVLDTDYYSNTSVPLIKQFPVTCETGPGSPSGHA 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 LLWVAVIGDWLNLVFKWILFGQRPYWWVLDTDYYSNTSVPLIKQFPVTCETGPGSPSGHA 120
Qy 121 MGTAGVYYVMVTSTLSIFQGKIKPTYRFRCLNVILWLGFWAVQLNVCLSRIYLAAHFPHQ 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 MGTAGVYYVMVTSTLSIFQGKIKPTYRFRCLNVILWLGFWAVQLNVCLSRIYLAAHFPHQ 180
Qy 181 VVAGVLSGIAVAETFSHIHSIYNASLKKYFLITFFLFSFAIGFYLLLKGLGVDLLWTLEK 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 VVAGVLSGIAVAETFSHIHSIYNASLKKYFLITFFLFSFAIGFYLLLKGLGVDLLWTLEK 240
Qy 241 AQRWCEQPEWVHIDTTPFASLLKNLGTLFGLGLALNSSMYRESCKGKLSKWLPFRLSCIV 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||| ||
Db 241 AQRWCEQPEWVHIDTTPFASLLKNLGTLFGLGLALNSSMYRESCKGKLSKWLPFRLSSIV 300
Qy 301 ASLVLLHVFDSLKPPSQVELVFYVLSFCKSAVVPLASVSVIPYCLAQVLGQPHKKSL 357
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 ASLVLLHVFDSLKPPSQVELVFYVLSFCKSAVVPLASVSVIPYCLAQVLGQPHKKSL 357
QY (SEQ ID NO: 2) vs. DB (SEQ ID NO: 6 of Chou)
Query Match 99.7%; Score 1070.8; DB 1; Length 1074;
Best Local Similarity 99.8%;
Matches 1072; Conservative 0; Mismatches 2; Indels 0; Gaps 0;
Qy 1 ATGGAGGAAGGAATGAATGTTCTCCATGACTTTGGGATCCAGTCAACACATTACCTCCAG 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 ATGGAGGAAGGAATGAATGTTCTCCATGACTTTGGGATCCAGTCAACACATTACCTCCAG 60
Qy 61 GTGAATTACCAAGACTCCCAGGACTGGTTCATCTTGGTGTCCGTGATCGCAGACCTCAGG 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 GTGAATTACCAAGACTCCCAGGACTGGTTCATCTTGGTGTCCGTGATCGCAGACCTCAGG 120
Qy 121 AATGCCTTCTACGTCCTCTTCCCCATCTGGTTCCATCTTCAGGAAGCTGTGGGCATTAAA 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 AATGCCTTCTACGTCCTCTTCCCCATCTGGTTCCATCTTCAGGAAGCTGTGGGCATTAAA 180
Qy 181 CTCCTTTGGGTAGCTGTGATTGGAGACTGGCTCAACCTCGTCTTTAAGTGGATTCTCTTT 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 CTCCTTTGGGTAGCTGTGATTGGAGACTGGCTCAACCTCGTCTTTAAGTGGATTCTCTTT 240
Qy 241 GGACAGCGTCCATACTGGTGGGTTTTGGATACTGACTACTACAGCAACACTTCCGTGCCC 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 GGACAGCGTCCATACTGGTGGGTTTTGGATACTGACTACTACAGCAACACTTCCGTGCCC 300
Qy 301 CTGATAAAGCAGTTCCCTGTAACCTGTGAGACTGGACCAGGGAGCCCCTCTGGCCATGCC 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 CTGATAAAGCAGTTCCCTGTAACCTGTGAGACTGGACCAGGGAGCCCCTCTGGCCATGCC 360
Qy 361 ATGGGCACAGCAGGTGTATACTACGTGATGGTCACATCTACTCTTTCCATCTTTCAGGGA 420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 361 ATGGGCACAGCAGGTGTATACTACGTGATGGTCACATCTACTCTTTCCATCTTTCAGGGA 420
Qy 421 AAGATAAAGCCGACCTACAGATTTCGGTGCTTGAATGTCATTTTGTGGTTGGGATTCTGG 480
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 421 AAGATAAAGCCGACCTACAGATTTCGGTGCTTGAATGTCATTTTGTGGTTGGGATTCTGG 480
Qy 481 GCTGTGCAGCTGAATGTCTGTCTGTCACGAATCTACCTTGCTGCTCATTTTCCTCATCAA 540
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 481 GCTGTGCAGCTGAATGTCTGTCTGTCACGAATCTACCTTGCTGCTCATTTTCCTCATCAA 540
Qy 541 GTTGTTGCTGGAGTCCTGTCAGGCATTGCTGTTGCAGAAACTTTCAGCCACATCCACAGC 600
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 541 GTTGTTGCTGGAGTCCTGTCAGGCATTGCTGTTGCAGAAACTTTCAGCCACATCCACAGC 600
Qy 601 ATCTATAATGCCAGCCTCAAGAAATATTTTCTCATTACCTTCTTCCTGTTCAGCTTCGCC 660
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 601 ATCTATAATGCCAGCCTCAAGAAATATTTTCTCATTACCTTCTTCCTGTTCAGCTTCGCC 660
Qy 661 ATCGGATTTTATCTGCTGCTCAAGGGACTGGGTGTAGACCTCCTGTGGACTCTGGAGAAA 720
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 661 ATCGGATTTTATCTGCTGCTCAAGGGACTGGGTGTAGACCTCCTGTGGACTCTGGAGAAA 720
Qy 721 GCCCAGAGGTGGTGCGAGCAGCCAGAATGGGTCCACATTGACACCACACCCTTTGCCAGC 780
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 721 GCCCAGAGGTGGTGCGAGCAGCCAGAATGGGTCCACATTGACACCACACCCTTTGCCAGC 780
Qy 781 CTCCTCAAGAACCTGGGCACGCTCTTTGGCCTGGGGCTGGCTCTCAACTCCAGCATGTAC 840
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 781 CTCCTCAAGAACCTGGGCACGCTCTTTGGCCTGGGGCTGGCTCTCAACTCCAGCATGTAC 840
Qy 841 AGGGAGAGCTGCAAGGGGAAACTCAGCAAGTGGCTCCCATTCCGCCTCAGCTGCATTGTA 900
|||||||||||||||||||||||||||||||||||||||||||||||||||| ||||||
Db 841 AGGGAGAGCTGCAAGGGGAAACTCAGCAAGTGGCTCCCATTCCGCCTCAGCTCTATTGTA 900
Qy 901 GCCTCCCTCGTCCTCCTGCACGTCTTTGACTCCTTGAAACCCCCATCCCAAGTCGAGCTG 960
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 901 GCCTCCCTCGTCCTCCTGCACGTCTTTGACTCCTTGAAACCCCCATCCCAAGTCGAGCTG 960
Qy 961 GTCTTCTACGTCTTGTCCTTCTGCAAGAGTGCGGTAGTGCCCCTGGCATCCGTCAGTGTC 1020
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 961 GTCTTCTACGTCTTGTCCTTCTGCAAGAGTGCGGTAGTGCCCCTGGCATCCGTCAGTGTC 1020
Qy 1021 ATCCCCTACTGCCTCGCCCAGGTCCTGGGCCAGCCGCACAAGAAGTCGTTGTAA 1074
||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1021 ATCCCCTACTGCCTCGCCCAGGTCCTGGGCCAGCCGCACAAGAAGTCGTTGTAA 1074
QY (SEQ ID NO: 8) vs. DB (SEQ ID NO: 133 of Von Maltzahn et al)
Query Match 100.0%; Score 406; DB 1; Length 1122;
Best Local Similarity 100.0%;
Matches 406; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 GTACCCGGGGATCTTGCTACCAGTGGAACAGCCACTAAGGATTCTGCAGTGAGAGCAGAG 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 325 GTACCCGGGGATCTTGCTACCAGTGGAACAGCCACTAAGGATTCTGCAGTGAGAGCAGAG 384
Qy 61 GGCCAGCTAAGTGGTACTCTCCCAGAGACTGTCTGACTCACGCCACCCCCTCCACCTTGG 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 385 GGCCAGCTAAGTGGTACTCTCCCAGAGACTGTCTGACTCACGCCACCCCCTCCACCTTGG 444
Qy 121 ACACAGGACGCTGTGGTTTCTGAGCCAGGTACAATGACTCCTTTCGGTAAGTGCAGTGGA 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 445 ACACAGGACGCTGTGGTTTCTGAGCCAGGTACAATGACTCCTTTCGGTAAGTGCAGTGGA 504
Qy 181 AGCTGTACACTGCCCAGGCAAAGCGTCCGGGCAGCGTAGGCGGGCGACTCAGATCCCAGC 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 505 AGCTGTACACTGCCCAGGCAAAGCGTCCGGGCAGCGTAGGCGGGCGACTCAGATCCCAGC 564
Qy 241 CAGTGGACTTAGCCCCTGTTTGCTCCTCCGATAACTGGGGTGACCTTGGTTAATATTCAC 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 565 CAGTGGACTTAGCCCCTGTTTGCTCCTCCGATAACTGGGGTGACCTTGGTTAATATTCAC 624
Qy 301 CAGCAGCCTCCCCCGTTGCCCCTCTGGATCCACTGCTTAAATACGGACGAGGACAGGGCC 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 625 CAGCAGCCTCCCCCGTTGCCCCTCTGGATCCACTGCTTAAATACGGACGAGGACAGGGCC 684
Qy 361 CTGTCTCCTCAGCTTCAGGCACCACCACTGACCTGGGACAGTGAAT 406
||||||||||||||||||||||||||||||||||||||||||||||
Db 685 CTGTCTCCTCAGCTTCAGGCACCACCACTGACCTGGGACAGTGAAT 730
QY (SEQ ID NO: 9) vs. DB (SEQ ID NO: 133 of Von Maltzahn et al)
Query Match 100.0%; Score 321; DB 1; Length 1122;
Best Local Similarity 100.0%;
Matches 321; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 AGGCTCAGAGGCACACAGGAGTTTCTGGGCTCACCCTGCCCCCTTCCAACCCCTCAGTTC 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 4 AGGCTCAGAGGCACACAGGAGTTTCTGGGCTCACCCTGCCCCCTTCCAACCCCTCAGTTC 63
Qy 61 CCATCCTCCAGCAGCTGTTTGTGTGCTGCCTCTGAAGTCCACACTGAACAAACTTCAGCC 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 64 CCATCCTCCAGCAGCTGTTTGTGTGCTGCCTCTGAAGTCCACACTGAACAAACTTCAGCC 123
Qy 121 TACTCATGTCCCTAAAATGGGCAAACATTGCAAGCAGCAAACAGCAAACACACAGCCCTC 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 124 TACTCATGTCCCTAAAATGGGCAAACATTGCAAGCAGCAAACAGCAAACACACAGCCCTC 183
Qy 181 CCTGCCTGCTGACCTTGGAGCTGGGGCAGAGGTCAGAGACCTCTCTGGGCCCATGCCACC 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 184 CCTGCCTGCTGACCTTGGAGCTGGGGCAGAGGTCAGAGACCTCTCTGGGCCCATGCCACC 243
Qy 241 TCCAACATCCACTCGACCCCTTGGAATTTCGGTGGAGAGGAGCAGAGGTTGTCCTGGCGT 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 244 TCCAACATCCACTCGACCCCTTGGAATTTCGGTGGAGAGGAGCAGAGGTTGTCCTGGCGT 303
Qy 301 GGTTTAGGTAGTGTGAGAGGG 321
|||||||||||||||||||||
Db 304 GGTTTAGGTAGTGTGAGAGGG 324
QY (SEQ ID NO: 7) vs. DB (SEQ ID NO: 133 of Von Maltzahn et al)
Query Match 100.0%; Score 727; DB 1; Length 1122;
Best Local Similarity 100.0%;
Matches 727; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 AGGCTCAGAGGCACACAGGAGTTTCTGGGCTCACCCTGCCCCCTTCCAACCCCTCAGTTC 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 4 AGGCTCAGAGGCACACAGGAGTTTCTGGGCTCACCCTGCCCCCTTCCAACCCCTCAGTTC 63
Qy 61 CCATCCTCCAGCAGCTGTTTGTGTGCTGCCTCTGAAGTCCACACTGAACAAACTTCAGCC 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 64 CCATCCTCCAGCAGCTGTTTGTGTGCTGCCTCTGAAGTCCACACTGAACAAACTTCAGCC 123
Qy 121 TACTCATGTCCCTAAAATGGGCAAACATTGCAAGCAGCAAACAGCAAACACACAGCCCTC 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 124 TACTCATGTCCCTAAAATGGGCAAACATTGCAAGCAGCAAACAGCAAACACACAGCCCTC 183
Qy 181 CCTGCCTGCTGACCTTGGAGCTGGGGCAGAGGTCAGAGACCTCTCTGGGCCCATGCCACC 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 184 CCTGCCTGCTGACCTTGGAGCTGGGGCAGAGGTCAGAGACCTCTCTGGGCCCATGCCACC 243
Qy 241 TCCAACATCCACTCGACCCCTTGGAATTTCGGTGGAGAGGAGCAGAGGTTGTCCTGGCGT 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 244 TCCAACATCCACTCGACCCCTTGGAATTTCGGTGGAGAGGAGCAGAGGTTGTCCTGGCGT 303
Qy 301 GGTTTAGGTAGTGTGAGAGGGGTACCCGGGGATCTTGCTACCAGTGGAACAGCCACTAAG 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 304 GGTTTAGGTAGTGTGAGAGGGGTACCCGGGGATCTTGCTACCAGTGGAACAGCCACTAAG 363
Qy 361 GATTCTGCAGTGAGAGCAGAGGGCCAGCTAAGTGGTACTCTCCCAGAGACTGTCTGACTC 420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 364 GATTCTGCAGTGAGAGCAGAGGGCCAGCTAAGTGGTACTCTCCCAGAGACTGTCTGACTC 423
Qy 421 ACGCCACCCCCTCCACCTTGGACACAGGACGCTGTGGTTTCTGAGCCAGGTACAATGACT 480
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 424 ACGCCACCCCCTCCACCTTGGACACAGGACGCTGTGGTTTCTGAGCCAGGTACAATGACT 483
Qy 481 CCTTTCGGTAAGTGCAGTGGAAGCTGTACACTGCCCAGGCAAAGCGTCCGGGCAGCGTAG 540
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 484 CCTTTCGGTAAGTGCAGTGGAAGCTGTACACTGCCCAGGCAAAGCGTCCGGGCAGCGTAG 543
Qy 541 GCGGGCGACTCAGATCCCAGCCAGTGGACTTAGCCCCTGTTTGCTCCTCCGATAACTGGG 600
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 544 GCGGGCGACTCAGATCCCAGCCAGTGGACTTAGCCCCTGTTTGCTCCTCCGATAACTGGG 603
Qy 601 GTGACCTTGGTTAATATTCACCAGCAGCCTCCCCCGTTGCCCCTCTGGATCCACTGCTTA 660
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 604 GTGACCTTGGTTAATATTCACCAGCAGCCTCCCCCGTTGCCCCTCTGGATCCACTGCTTA 663
Qy 661 AATACGGACGAGGACAGGGCCCTGTCTCCTCAGCTTCAGGCACCACCACTGACCTGGGAC 720
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 664 AATACGGACGAGGACAGGGCCCTGTCTCCTCAGCTTCAGGCACCACCACTGACCTGGGAC 723
Qy 721 AGTGAAT 727
|||||||
Db 724 AGTGAAT 730