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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 07/28/2025 has been entered.
Election/Restrictions
Claims 34, 66, 74-76, 81-93 are pending.
Claims of elected Group II, 34, 74-76, 82-83 and the new claims 84-93 are examined here along with the elected species of a 3’-UTR from a PSMB gene.
Claims 66 and 81 stand withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.
Priority
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55. Thus, priority to PCT/EP2018/058784, filed on 04/05/2018 is recognized. All examined claims enjoy the priority filing date of ‘784.
Claim Objections
Objection to claim 74 is withdrawn, the claims abbreviated terms are spelled out at first instance of recitation.
Claim Rejections - 35 USC § 112
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 34, 74, 75, 76, 82-83, 85-93 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Amended claim 34 recites the limitation "sterol" in the last line of claim 34. One is a species (sterol), while the other is a genus (steroid) and are distinct from each other. There is insufficient antecedent basis or a broad range or limitation together with a narrow range or limitation for this limitation in the claim.
In the interest of compact prosecution, if the prior art discloses a species, e.g. a cholesterol, the claim will be interpreted to read on the broader terms of sterol and steroid.
Claim Rejections - 35 USC § 103
Rejection of claims 34, and 74-76, 82-83 is maintained and the new claims 84-93 are rejected as noted below.
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 34, 76, 82-86, 89, 90-91 are rejected under 35 U.S.C. 103 as being unpatentable over Ciaramella et al. (US20190060438, pub. 02/28/2019, EFD: 10/28/2015 to 62/247,527, referred as Ciaramella and is a 102(a)(2) reference) and Lee et al. (US20110287519, pub. 11/24/2011, referred as Lee) and as evidenced by Issa et al. (WO2014152030, pub. 09/25/2014) for claim 76.
Ciaramella discloses a mRNA vaccine for an immune response to various flaviviruses, including Chikungunya virus (CHIKV), Zika Virus (ZIKV) and Dengue virus (DENV) (par. 12); discloses that the yellow fever virus is in the same flavivirus genus (par. 10); discloses a mRNA comprising a 5’UTR, an open reading frame, a 3’-UTR and a polyA tail (par. 218), with the polyA tail of 10-300 nt. and recites a specific 150 nt. poly A tail length (par. 222), discloses the mRNA produces an immunogenic epitope (par. 199-201); discloses in “some embodiments, the 5’ terminal cap is 7mG(5′)ppp(5′)NlmpNp” (par. 65), and as evidenced by Issa et al. (WO2014152030, pub. 09/25/2014) it is also known as Cap1 (par. 67, relevant to instant cl. 34, 76).
Ciaramella also discloses an RNA vaccine formulated in a lipid nanoparticle (LNP) carrier, which is composed of a cationic lipid, a PEG-modified lipid, a sterol and a non-cationic lipid, which is a neutral lipid (par. 72, par. 416, 485 disclose an example of a vaccine formulation with LNP comprising DLin-MC3-DMA (a cationic lipid), DSPC (a neutral lipid), a PEG-lipid, and cholesterol (a steroid)), and discloses that LNP comprises a molar ratio of about 20-60% cationic lipid, 5-25% non-cationic lipid, 25-55% sterol, and 0.5-15% PEG-modified lipid (par. 72, relevant to instant cl. 34, 84).
Ciaramella discloses a broader range of polyA sequence than the instant claims. MPEP 2144.05(I) provides that in the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. Here, the claimed ranges (30-150 adenosine nt.) lie inside the prior art range (10-300 adenosine nt.), thus providing a prima facie case of obviousness for the polyA tail. Further Ciaramella discloses RNA vaccines, such as mRNA vaccine, can be used “to provide a balanced immune response against a single virus” without the “safety concerns, e.g. risking the possibility of insertional mutagenesis” (par. 12, relevant to instant cl. 86).
However, Ciaramella does not disclose an amino acid sequence that is least 90% identical to the amino acid sequence of SEQ ID NO: 121. or an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 2201.
Lee discloses developing a safer, attenuated yellow fever vaccine (YFV) of a 17D strain (“unadapted virus”) to achieve higher yields in a cell culture for vaccine production through serial passaging of YFV 17D strain (par. 12, 51, 53); the amino acid sequence derived from the nucleic acid sequence of the 17D strain produces SEQ ID NO: 3, a 3411 amino acid (a.a.) polycistronic polypeptide product that comprises prM, E and NS1 proteins, amongst other proteins, of YFV (see Fig. 5A, par. 44). The amino acid sequence of Lee SEQ ID NO: 3 from a.a. position 92 to 788 matches 696 out of 697 amino acids of instant SEQ ID NO: 121 (Instant SEQ ID NO: 121 had a similar 99% match with various sequences of Lee, including SEQ ID NOs: 3, 4, 5, 6, 7, 8, 13, 14; see alignment comparing instant SEQ ID NO: 121 and Lee’s SEQ ID NO: 3; relevant to instant cl. 34). Further, the amino acid positions 758-1177 of Lee SEQ ID NO: 3 are 100% identical to instant SEQ ID NO: 2201, a 420 a.a. sequence (see Fig. 5A, par. 44; see alignment below between instant SEQ ID NO: 2201 and Lee’s SEQ ID NO: 3; relevant to instant cl. 34). Thus Lee SEQ ID NO: 3 comprises both instant SEQ ID NOs: 121 and 2201. Lee discloses methods of making and using the nucleic acid molecules, modified E proteins and modified NS1 proteins (par. 37); and discloses an example of serial passaging of unadapted virus 17D strain to adapted, improved 17D strain in vitro and demonstrates “robust neutralizing antibody titers can be achieved in mice immunized with 2 or more inoculations of the disclosed YF virus” (par. 116, Fig. 3B, 3C, shows that both the unadapted and adapted 17D strain produce antibodies).
One of the KSR rationale that may be used to support a conclusion of obviousness is that there is some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention. Therefore, it would have been prima facie obvious for one of ordinary skill in the art before the filing date of the claimed invention to have modified the ORF of a flavivirus in a mRNA vaccine of Ciaramella in view of Lee and arrive at the claimed invention with a reasonable expectation of success. Based on Ciaramella disclosing the need to generate a mRNA vaccine for safety concerns and Lee disclosing that nucleic acid sequence encoding for NS1 of YFV generates a robust neutralizing antibody titer, a skilled artisan would reasonably expect success in producing a safer vaccine by substituting ORF of a mRNA vaccine against flavivirus of Ciaramella with an attenuated YF viral nucleotide sequence of SEQ ID NO: 3, comprising a sequence encoding prME and NS1 protein, of Lee. Thus, claims 34, 76, 84, 86 are obvious.
Regarding instant claims 82 and 83, the claims recite “wherein the at least one antigenic peptide or protein derived from a Yellow fever virus prME polyprotein is encoded by a RNA sequence at least 85% identical to the RNA sequence of SEQ ID NO: 195” and “at least 90% identical to the RNA sequence of SEQ ID NO: 195,” respectively.
The minimum requirement for both claims is that at least “one antigenic peptide” derived from a YFV prME polyprotein is encoded by “a RNA sequence,” which, under BRI, is interpreted as any RNA sequence of any length that has at least 85% (or 90%) identity to the RNA sequence of SEQ ID NO: 195 and produces one antigenic peptide. Further, antigenic determinant epitope, as defined by the specification, notes that T cell epitopes or parts of the antigenic peptides or proteins may comprise fragments preferably having a length of about 6 to about 20 or even more amino acids (par. 37).
Aligning the relevant sequence of instant SEQ ID NO: 195 with Lee SEQ ID NO: 1 (this is passage 1 consensus sequence, par. 43) from nt. position 392 to 1080, which comprises a RNA sequence encoding at least one antigenic peptide of the polypeptide of YFV prME, there is a 74% identity (see Alignment 3 below). However, there is a stretch of a ~40 nt. sequence of Lee SEQ ID NO: 1 that would generate at least one antigenic peptide from position 199 to 240 (14 a.a., see underlined portion of alignment 3 below) and matches with 88% with instant SEQ ID NO: 195 (relevant to instant cl. 82), while a shorter nucleotide sequence from 199 with 217 of SEQ ID NO: 1 of Lee matches 94% and would generate a peptide of 6 a.a. (see underlined portion of alignment 3 below, relevant to instant cl. 82, 83). There is a 99.9% identity between SEQ ID NO: 1 and SEQ ID NO: 2 (passage 11, an adapted safer virus, par. 43).
Thus based on effective producing a titer from passage 1 (SEQ ID NO: 1) to passage 11 (SEQ ID NO: 2) of Lee and Ciaramella noting the safer purpose of using mRNA-based vaccine, it would reasonable for a skilled artisan to expect success of substituting an ORF of a flavivirus in a mRNA vaccine of Ciaramella with RNA sequence of SEQ ID NO: 1 of Lee to generate a peptide for production of antibodies for production of antibodies against relevant proteins of YFV virus.
Regarding instant claim 85, Ciaramella discloses the lipid nanoparticles has a mean diameter of 50-200 nm. Here the claimed range lies inside the range disclosed Ciaramella, thus is prima facie obvious under MPEP 2144.05(I). Diameter is diameter regardless how it is measured, unless DLS measurements are substantially different from known methods of measuring diameter of a LNP.
Regarding instant cl. 89, requires that cap1 is further modified. Thus, based on the use of a modified base, a pseudouridine, of Ciaramella within the terminal nucleotides of Cap1 structure of Ciaramella, a skilled artisan understands the purpose of capped mRNA is to stabilize the mRNA (par. 328) and can introduce a modified base by chemical synthesis method (par. 394). Thus, claim 89 is obvious.
Regarding instant cl. 90 and 91, Ciaramella discloses that a chemical modification can be selected from various modified nucleotides, including pseudouridine or 1-methyl-pseudouridine (par. 68).
Claims 74 and 75 are rejected under 35 U.S.C. 103 as being unpatentable over Ciaramella et al. (US20190060438, pub. 02/28/2019, EFD: 10/28/2015 to 62/247,527, referred as Ciaramella and is a 102(a)(2) reference) and Lee et al. (US20110287519, pub. 11/24/2i011, referred as Lee) as applied to claims 34, 76, 82-86, 89, 90-91 above, and further in view of Trinklein et al. (US20080220983, pub. 09/11/2008, hereinafter referred as Trinklein, of record).
The specification discloses PSMB3 3’UTR comprises 70%-99% of SEQ ID NO: 15, a 57 nt. sequence.
The disclosure pertaining to rejection of claims 34, 76, 82-86, 89, 90-91 is above.
Ciaramella and Lee do not disclose 3’-UTR of elected PSMB3 gene.
Trinklein discloses a characterization of various regulatory elements, including 5’ and/or 3’-UTR, operably linked to reporter genes (Abstract). Trinklein discloses a method of producing a 3’UTR expression construct (Fig. 3, par. 24); discloses the importance of the 3’-UTR in regulating stability, transport, and/or translation rate of the mRNA transcript (par. 32); further discloses the importance elucidating 3’ UTR function (par. 32, 89); discloses a UTR sequence of SEQ ID NO: 6761, which is 100% identical to instant SEQ ID NO: 15 (see alignment below, Qy is instant SEQ ID NO: 195, Db is SEQ ID NO: 6761 of Trinklein).
US-12-074-856-6761
(NOTE: this sequence has 43 duplicates in the database searched.
See complete list at the end of this report)
Sequence 6761, US/12074856
Publication No. US20080220983A1
GENERAL INFORMATION
APPLICANT: Trinklein, Nathan D
APPLICANT: Aldred, Shelley Force
TITLE OF INVENTION: FUNCTIONAL ARRAYS FOR HIGH THROUGHPUT CHARACTERIZATION OF REGULATORY
TITLE OF INVENTION: ELEMENTS IN UNTRANSLATED REGIONS OF GENES
FILE REFERENCE: SGG08
CURRENT APPLICATION NUMBER: US/12/074,856
CURRENT FILING DATE: 2008-03-05
NUMBER OF SEQ ID NOS: 17520
SEQ ID NO 6761
LENGTH: 57
TYPE: DNA
ORGANISM: Homo sapiens
Query Match 100.0%; Score 57; Length 57;
Best Local Similarity 100.0%;
Matches 57; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 CCCTGTTCCCAGAGCCCACTTTTTTTTCTTTTTTTGAAATAAAATAGCCTGTCTTTC 57
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 CCCTGTTCCCAGAGCCCACTTTTTTTTCTTTTTTTGAAATAAAATAGCCTGTCTTTC 57
One of the KSR rationale that may be used to support a conclusion of obviousness is that there is some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention. Therefore, it would have been prima facie obvious for one of ordinary skill in the art before the filing date of the claimed invention to have modified the 3’-UTR of Ciaramella in view of Trinklein and arrive at the claimed invention with a reasonable expectation of success. A skilled artisan recognizing the similar function of a 3’-UTR would have been motivated to substitute 3’-UTR of Ciaramella to test various other 3’-UTRs, including SEQ ID NO: 6761, of Trinklein, to elucidate the function of 3’-UTR of PSMB3 and have reasonable expectation of success of expressing the construct or understanding the function of 3’-UTR of SEQ ID NO: 6761 relative to 3’-UTR of other genes.
Claims 87-88 are rejected under 35 U.S.C. 103 as being unpatentable over Ciaramella et al. (US20190060438, pub. 02/28/2019, EFD: 10/28/2015 to 62/247,527, referred as Ciaramella and is a 102(a)(2) reference) and Lee et al. (US20110287519, pub. 11/24/2011, referred as Lee) as applied to claims 34, 76, 82-86, 89, 90-91 above, and further in view Kim et al. (2014, PNAS, 111, 10708-10713, referred as Kim).
Disclosure pertaining rejection of claims 34, 76, 82-86, 89, 90-91 is noted above.
Ciaramella and Lee do not disclose a replicon RNA (cl. 87) or that replicon RNA comprises a replicase RNA sequence derived from VEE (cl. 88).
The specification defines replicon RNA as an optimized self-replicating artificial RNA constructs, including replication elements (replicase) derived from alphavirus (pg. 44, lines 20-23).
Kim discloses the use of “alphaviruses have become an attractive system for expression of heterologous genetic information” to express heterologous proteins since “[a]lphaviruses replicate exclusively in the cytoplasm, and their genetic material cannot recombine with cellular DNA” (abstract, pg. 10708). Kim created a construct of incorporating replicon elements of VEEV genome (see Fig. 1C, nsP1-4, with nsp4 known in the art as a replicase, pg. 10709, relevant to instant cl. 87-88). Kim confirmed the replicon’s use in vivo for the production of a flavivirus west-Nile virus (WNV) envelope protein when the replicon comprised RNA encoding WNV prM/E proteins (see Fig. 5, pg. 10711). Kim highlighted that using this modified VEEV replicon with “encoded proteins of interest 10- to 50-fold more efficiently than using a traditional design” (abstract).
One of the KSR rationale that may be used to support a conclusion of obviousness is that there is some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention. Therefore, it would have been prima facie obvious for one of ordinary skill in the art before the filing date of the claimed invention to have modified the mRNA vaccine of Ciaramella comprising ORF of SEQ ID NO: 3/1 of Lee in view of Kim and arrive at the claimed invention with a reasonable expectation of success. Based on success of Kim producing efficient heterologous proteins for vaccine production and Ciaramella and Lee providing sequences to produce mRNA encoding antigens YFV prME, a skilled artisan would reasonably expect success in expressing the mRNA of Ciaramella incorporated into a VEEV replicon of Kim to produce a safer and more efficient vaccine since it replicates in the cytoplasm. Thus, claims 87-88 are obvious.
Claims 92 and 93 are rejected under 35 U.S.C. 103 as being unpatentable over Ciaramella et al. (US20190060438, pub. 02/28/2019, EFD: 10/28/2015 to 62/247,527, referred as Ciaramella and is a 102(a)(2) reference) and Lee et al. (US20110287519, pub. 11/24/2011, referred as Lee) as applied to claims 34, 76, 82-86, 89, 90-91 above, and further in view of Derosa et al. (US20150376220, pub. 12/31/2015, referred as Derosa).
Disclosure pertaining rejection of claims 34, 76, 82-86, 89, 90-91 is noted above.
Ciaramella and Lee do not disclose TFF purification (cl. 92, 93).
Derosa discloses “a great need for a large scale production of highly pure and safer mRNA product suitable for therapeutic use” (par. 2) and discloses purifying mRNA following in vitro transcription at large scale (up to 25 g scale) using tangential flow filtration (TFF) (par. 167, 158). Fig. 18 demonstrates that human ASS1 protein production after transfection of the mRNA purified with TFF (“5G”) resulted in increased protein production compared to spin-column purified mRNA (par. 51, 163).
One of the KSR rationale that may be used to support a conclusion of obviousness is that there is some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention. Therefore, it would have been prima facie obvious for one of ordinary skill in the art before the filing date of the claimed invention to have purified the mRNA product of Ciaramella in view of DeRosa and arrive at the claimed invention with a reasonable expectation of success. Based on successfully purifying mRNA products produced via in vitro transcription using TFF and the purified mRNA leading to increased protein production of DeRosa, a skilled artisan would purify the mRNA products of Ciaramella using TFF of DeRosa resulting in safer and purer mRNA with increased protein production. Thus, claims 92 and 93 are obvious.
Response to Arguments
Applicant's arguments filed 07/28/2025 (“the Remarks”) have been fully considered but they are not persuasive.
The Remarks insist that combination of prior art references fail to teach or suggest that combination of at least one antigenic peptide or protein derived from a YFV prME polyprotein, which is at least 90% identical to the amino acid sequence of SEQ ID NO: 121 and a YFV NS1 protein, which is at least 90% identical to the amino acid sequence of SEQ ID NO: 2201 (pg. 5-6). The Remarks add that since the art do not teach elements of independent claim 34, then all other claims are free of the art (pg. 6).
The argument is not persuasive.
As noted in prior action and this action, SEQ ID NO: 3 amino acid sequence, a polypeptide comprising prME of YFV, of Lee comprises both instant SEQ ID NO: 121 and 2201 (see alignment below). Ciaramella further teach that ORF of interest can be incorporated into a mRNA. Thus, the rejection is maintained.
Allowable Subject Matter
No claim allowed.
Sequence Alignments:
ALIGNMENT of instant SEQ ID NO: 121 (Qy) and Lee SEQ ID NO: 3 (Db)
Query Match 99.8%; Score 3682; Length 3411;
Best Local Similarity 99.9%;
Matches 696; Conservative 0; Mismatches 1; Indels 0; Gaps 0;
Qy 1 MRGLSSRKRRSHDVLTVQFLILGMLLMTGGVTLVRKNRWLLLNVTSEDLGKTFSVGTGNC 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 92 MRGLSSRKRRSHDVLTVQFLILGMLLMTGGVTLVRKNRWLLLNVTSEDLGKTFSVGTGNC 151
Qy 61 TTNILEAKYWCPDSMEYNCPNLSPREEPDDIDCWCYGVENVRVAYGKCDSAGRSRRSRRA 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 152 TTNILEAKYWCPDSMEYNCPNLSPREEPDDIDCWCYGVENVRVAYGKCDSAGRSRRSRRA 211
Qy 121 IDLPTHENHGLKTRQEKWMTGRMGERQLQKIERWFVRNPFFAVTALTIAYLVGSNMTQRV 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 212 IDLPTHENHGLKTRQEKWMTGRMGERQLQKIERWFVRNPFFAVTALTIAYLVGSNMTQRV 271
Qy 181 VIALLVLAVGPAYSAHCIGITDRDFIEGVHGGTWVSATLEQDKCVTVMAPDKPSLDISLE 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 272 VIALLVLAVGPAYSAHCIGITDRDFIEGVHGGTWVSATLEQDKCVTVMAPDKPSLDISLE 331
Qy 241 TVAIDRPAEVRKVCYNAVLTHVKINDKCPSTGEAHLAEENEGDNACKRTYSDRGWGNGCG 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 332 TVAIDRPAEVRKVCYNAVLTHVKINDKCPSTGEAHLAEENEGDNACKRTYSDRGWGNGCG 391
Qy 301 LFGKGSIVACAKFTCAKSMSLFEVDQTKIQYVIRAQLHVGAKQENWNTDIKTLKFDALSG 360
|||||||||||||||||||||||||||||||||||||||||||||| |||||||||||||
Db 392 LFGKGSIVACAKFTCAKSMSLFEVDQTKIQYVIRAQLHVGAKQENWTTDIKTLKFDALSG 451
Qy 361 SQEVEFIGYGKATLECQVQTAVDFGNSYIAEMETESWIVDRQWAQDLTLPWQSGSGGVWR 420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 452 SQEVEFIGYGKATLECQVQTAVDFGNSYIAEMETESWIVDRQWAQDLTLPWQSGSGGVWR 511
Qy 421 EMHHLVEFEPPHAATIRVLALGNQEGSLKTALTGAMRVTKDTNDNNLYKLHGGHVSCRVK 480
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 512 EMHHLVEFEPPHAATIRVLALGNQEGSLKTALTGAMRVTKDTNDNNLYKLHGGHVSCRVK 571
Qy 481 LSALTLKGTSYKICTDKMFFVKNPTDTGHGTVVMQVKVSKGAPCRIPVIVADDLTAAINK 540
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 572 LSALTLKGTSYKICTDKMFFVKNPTDTGHGTVVMQVKVSKGAPCRIPVIVADDLTAAINK 631
Qy 541 GILVTVNPIASTNDDEVLIEVNPPFGDSYIIVGRGDSRLTYQWHKEGSSIGKLFTQTMKG 600
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 632 GILVTVNPIASTNDDEVLIEVNPPFGDSYIIVGRGDSRLTYQWHKEGSSIGKLFTQTMKG 691
Qy 601 VERLAVMGDTAWDFSSAGGFFTSVGKGIHTVFGSAFQGLFGGLNWITKVIMGAVLIWVGI 660
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 692 VERLAVMGDTAWDFSSAGGFFTSVGKGIHTVFGSAFQGLFGGLNWITKVIMGAVLIWVGI 751
Qy 661 NTRNMTMSMSMILVGVIMMFLSLGVGADQGCAINFGK 697
|||||||||||||||||||||||||||||||||||||
Db 752 NTRNMTMSMSMILVGVIMMFLSLGVGADQGCAINFGK 788
2. ALIGNMENT of instant SEQ ID NO: 2201 (Qy) and Lee SEQ ID NO: 3 (Db)
Query Match 100.0%; Score 2278; Length 3411;
Best Local Similarity 100.0%;
Matches 420; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 MSMSMILVGVIMMFLSLGVGADQGCAINFGKRELKCGDGIFIFRDSDDWLNKYSYYPEDP 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 758 MSMSMILVGVIMMFLSLGVGADQGCAINFGKRELKCGDGIFIFRDSDDWLNKYSYYPEDP 817
Qy 61 VKLASIVKASFEEGKCGLNSVDSLEHEMWRSRADEINAIFEENEVDISVVVQDPKNVYQR 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 818 VKLASIVKASFEEGKCGLNSVDSLEHEMWRSRADEINAIFEENEVDISVVVQDPKNVYQR 877
Qy 121 GTHPFSRIRDGLQYGWKTWGKNLVFSPGRKNGSFIIDGKSRKECPFSNRVWNSFQIEEFG 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 878 GTHPFSRIRDGLQYGWKTWGKNLVFSPGRKNGSFIIDGKSRKECPFSNRVWNSFQIEEFG 937
Qy 181 TGVFTTRVYMDAVFEYTIDCDGSILGAAVNGKKSAHGSPTFWMGSHEVNGTWMIHTLEAL 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 938 TGVFTTRVYMDAVFEYTIDCDGSILGAAVNGKKSAHGSPTFWMGSHEVNGTWMIHTLEAL 997
Qy 241 DYKECEWPLTHTIGTSVEESEMFMPRSIGGPVSSHNHIPGYKVQTNGPWMQVPLEVKREA 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 998 DYKECEWPLTHTIGTSVEESEMFMPRSIGGPVSSHNHIPGYKVQTNGPWMQVPLEVKREA 1057
Qy 301 CPGTSVIIDGNCDGRGKSTRSTTDSGKVIPEWCCRSCTMPPVSFHGSDGCWYPMEIRPRK 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1058 CPGTSVIIDGNCDGRGKSTRSTTDSGKVIPEWCCRSCTMPPVSFHGSDGCWYPMEIRPRK 1117
Qy 361 THESHLVRSWVTAGEIHAVPFGLVSMMIAMEVVLRKRQGPKQMLVGGVVLLGAMLVGQVT 420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1118 THESHLVRSWVTAGEIHAVPFGLVSMMIAMEVVLRKRQGPKQMLVGGVVLLGAMLVGQVT 1177
Alignment between instant SEQ ID NO: 195 (Qy) and Lee SEQ ID NO: 1 pos. 392-1080 (Db)(512/689=74% identity)
Query Match 19.4%; Score 405.8; DB 1; Length 689;
Best Local Similarity 60.1%;
Matches 414; Conservative 98; Mismatches 177; Indels 0; Gaps 0;
Qy 1 AUGCGGGGCCUGAGCUCCCGCAAGCGGCGCAGCCACGACGUGCUCACCGUCCAGUUCCUG 60
|:| | || :| |:| | || || || ||| || |: |: || |: || ::||:
Db 1 ATGAGAGGATTGTCCTCAAGGAAACGCCGTTCCCATGATGTTCTGACTGTGCAATTCCTA 60
Qy 61 AUCCUGGGGAUGCUCCUGAUGACCGGCGGGGUGACGCUGGUGCGGAAGAACCGCUGGCUC 120
|: :||| |:||: :||:||| || || |:||| :||:|||||| ||| | :|| :
Db 61 ATTTTGGGAATGCTGTTGATGACGGGTGGAGTGACCTTGGTGCGGAAAAACAGATGGTTG 120
Qy 121 CUGCUGAACGUCACCUCCGAGGACCUCGGCAAGACCUUCAGCGUGGGGACCGGCAACUGC 180
|: |: || |: || :| |||||||:||| || || ::| |:||| || ||||||:||
Db 121 CTCCTAAATGTGACATCTGAGGACCTCGGGAAAACATTCTCTGTGGGCACAGGCAACTGC 180
Qy 181 ACGACCAACAUCCUGGAGGCCAAGUACUGGUGCCCCGACUCCAUGGAGUACAACUGCCCG 240
|| || ||||: :||| ||||||:||:||:|||| |||:| |:||| :|||||:| ||
Db 181 ACAACAAACATTTTGGAAGCCAAGTACTGGTGCCCAGACTCAATGGAATACAACTGTCCC 240
Qy 241 AACCUGAGCCCCCGGGAGGAGCCCGACGACAUCGACUGCUGGUGCUACGGCGUGGAGAAC 300
|| |: || || | |||||||| || ||||: || :||:||:||:| || |:||| |||
Db 241 AATCTCAGTCCAAGAGAGGAGCCAGATGACATTGATTGCTGGTGCTATGGGGTGGAAAAC 300
Qy 301 GUCCGCGUGGCCUACGGGAAGUGCGACUCCGCGGGCCGGAGCCGCCGGUCCCGCCGGGCC 360
|: | |: || :| || |||:| |||:| || ||| || | ||:| | |||||
Db 301 GTTAGAGTCGCATATGGTAAGTGTGACTCAGCAGGCAGGTCTAGGAGGTCAAGAAGGGCC 360
Qy 361 AUCGACCUCCCCACCCACGAGAACCACGGGCUGAAGACCCGCCAGGAGAAGUGGAUGACG 420
|: ||| : || || || || ||||| || :||||||||| || || || :|||:|||
Db 361 ATTGACTTGCCTACGCATGAAAACCATGGTTTGAAGACCCGGCAAGAAAAATGGATGACT 420
Qy 421 GGCCGGAUGGGGGAGCGCCAGCUGCAGAAGAUCGAGCGGUGGUUCGUGCGCAACCCGUUC 480
|| | |:||| || | || |: || ||||: ||| | :||::||:| | ||||| ::
Db 421 GGAAGAATGGGTGAAAGGCAACTCCAAAAGATTGAGAGATGGTTCGTGAGGAACCCCTTT 480
Qy 481 UUCGCCGUCACCGCCCUCACCAUCGCCUACCUGGUGGGCAGCAACAUGACCCAGCGGGUG 540
:: || |: || || |: ||||: |||:|||: |:||| |||||||:||| || || |:
Db 481 TTTGCAGTGACGGCTCTGACCATTGCCTACCTTGTGGGAAGCAACATGACGCAACGAGTC 540
Qy 541 GUCAUCGCGCUGCUCGUGCUGGCCGUGGGCCCCGCCUACUCCGCCCACUGCAUCGGGAUC 600
|: |: || |: |: |: :||| |: || || |||:||:| || |||:|||: || |:
Db 541 GTGATTGCCCTACTGGTCTTGGCTGTTGGTCCGGCCTACTCAGCTCACTGCATTGGAATT 600
Qy 601 ACGGACCGCGACUUCAUCGAGGGCGUCCACGGGGGCACCUGGGUGAGCGCGACCCUGGAG 660
|| ||| | || ::||: ||||| |: || || || || :|||: || ||||:||||
Db 601 ACTGACAGGGATTTCATTGAGGGGGTGCATGGAGGAACTTGGGTTTCAGCTACCCTGGAG 660
Qy 661 CAGGACAAGUGCGUGACCGUCAUGGCCCC 689
|| ||||||:| |: || |: |:||||||
Db 661 CAAGACAAGTGTGTCACTGTTATGGCCCC 689
Conclusion
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/KEYUR A VYAS/ Examiner, Art Unit 1637
/Soren Harward/Primary Examiner, TC 1600