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 .
This is a Final Office Action in response to amendment filed on 08/12/2026.
Claim Status
Claims 1, 2, 4, 7, 10, 16, 18, 29, 45, and 53 are pending. Claims 33, 38, 55, 58, 61, 65, 72, 74, 76, and 77 are withdrawn as a result of Restriction Requirement. Claims 1, 4, and 7 are currently amended. Claims 1, 2, 4, 7, 10, 16, 18, 29, 45, and 53 are examined on the merits.
Response to Amendment
The rejection of Claims 4 and 7 rejected under 35 U.S.C. 112(b) is withdrawn in view of amendment to the claims.
The rejection of Claims 1 and 4 rejected under 35 USC § 102(a)(1 ) is withdrawn in view of amendment to the claims. However, claims 1 and 4 are now rejected under 35 U.S.C. §103 for the reasons set forth below.
The rejection of claims 2, 7, 10, 16, 18, 29, 45, and 53 rejected under 35 U.S.C. §103 is maintained, but is modified in view of the amendments to the claims. The modified rejection set forth below constitutes a new ground of rejection necessitated by Applicant’s amendment.
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.
Claims 1 and 4 are rejected under 35 U.S.C. §103 as being unpatentable over Maliga (Pal Maliga et. al., US5877402A, Application: 1994-01-31, Publication: 1999-03-02) in view of Zhou (Fei Zhou et. al., The Plant Journal (2007) 52, 961–972).
Claim 1 recites a transformation vector for stably transforming a plastid, said transformation vector comprising: an expression cassette comprising, as operably-linked components, a regulatory sequence operative in the plastid, a heterologous polynucleotide sequence coding for a protein of interest, and a spacer region comprising about 50 to about 80 base pairs, wherein the spacer is from between rps2 and atp1 genes, psbN and psbH genes, or rpoC2 and rps2 genes of the plastid genome, and flanking each side of the expression cassette, a first DNA flanking sequence and a second flanking DNA sequence which allow for stable integration of the heterologous polynucleotide sequence coding for the protein of interest into the plastid genome.
Maliga teaches a transformation vector for stably transforming a plastid (claim 1), comprising a transforming DNA construct/vector having a targeting segment with plastid DNA homologous to a predetermined plastid genomic sequence, thereby enabling insertion into the plastid genome by homologous recombination (claim 1a). Maliga further teaches a selectable marker gene and at least one additional expressible DNA segment disposed within the targeting segment, wherein the expressible DNA segment contains a coding segment encoding a gene product (claim 1bi). Maliga further teaches targeting insertion of heterologous sequence with homologous plastid DNA insertion (column 21, line 30-45). Maliga teaches a 5’regulatory segment of plant chloroplast origin operably linked to the coding segment to promote expression in plastid (claim 1bii), and a 3’regulatory segment of a plant chloroplast mRNA molecule operably linked to the coding segment to promote stability of mRNA produced during expression (claim 1(b)(iii)).
Thus, Maliga teaches an expression cassette comprising, as operably linked components, a regulatory sequence operative in the plastid and a heterologous polynucleotide sequence coding for a protein of interest.
Maliga also teaches that the construct includes plastid DNA sequence flanking the expression elements which enable stable integration into the plastid genome by homologous recombination (claim 1a and claim 3a), thereby teaches flanking each side of the expression cassette, a first DNA flanking sequence and a second DNA flaking sequence which allow for stable integration of the heterologous polynucleotide sequence coding for the protein of interested into the plastid genome.
Maliga does not expressly teach the recited spacer region comprising about 50-80 base pairs from between rps2 and aptI gene, psbN and psbH genes, or rpoC2 and rps2 genes.
Zhou teaches plastid transformation constructs comprising intercistronic expression elements derived from the psbT-psbH intergenic spacer. Zhou specifically identities the relevant 3’ portion of the spacer as being between the antisense psbN sequence and psbH (Figure 1b). Zhou further teaches construct pZF75 containing the complete-25 to +25 sequence surrounding the psbT-psbH processing site, i.e., a 50-base-pair intercistronic expression element (Figure 1 and 2; Table 1). Zhou teaches that this 50-bp element was incorporated between the nptII and yfp genes in a plastid transformation construct and that significant amounts of stable monocistronic yfp mRNA accumulated with the complete +/- 25 element (p966, right column, pa2).
It would have been obvious to one of ordinary skill in the art at the time of the invention to incorporate the 50-bp psbN/psbH-region intercistronic element taught by Zhou into the plastid expression cassette of Maliga because Zhou teaches that this element facilitates RNA processing and stable accumulation of translatable downstream transcripts in plastids. Zhou further demonstrates successful plastid transformation using constructs containing the element, thereby providing a reasonable expectation of success.
Accordingly, claim 1 is obvious over Maliga in view of Zhou.
Claim 4 recites the vector of claim 1, wherein the first and second flanking sequences are substantially homologous have at least 95% sequence identity to sequences around an integration site of the plastid genome and provide for homologous recombination to insert the heterologous polynucleotide coding for the protein of interest into the integration site of the plastid genome.
As set forth for the same reasons as claim 1, Maliga teaches a transformation vector comprising an expression cassette and flanking sequences that allow for stable integration into the plastid genome. Further, Maliga teaches that the flanking sequences are homologous to plastid genomic sequences and mediate homologous recombination to insert the heterologous polynucleotide into the plastid genome (claim 1, column 21, line 30-45).
Malig further identifies the pRV1 plastid targeting segment as SEQ ID NO: 3, with the 5’ targeting segment comprising SEQ ID NO: 3 nucleotides 1-1790 and the 3’targeting segment comprising SEQ ID NO: 3 nucleotides 1791-2962 (p24, Figure 19B). Sequence comparison of the pPRV1 target sequence (GenBank U12809.1) with a corresponding Nicotiana plastid genomic sequence demonstrates approximately 99% sequence identity, which is greater than the claimed at least 95% sequence identity (See sequence and alignment below).
Therefore, Maliga teaches the additional flanking-sequence limitations of claim 4, and for the same reasons set forth for claim 1 regarding the spacer limitation, claim 4 is obvious over Maliga in view of Zhou.
Claims 2, 7, and 10 are rejected under 35 U.S.C. §103 as being unpatentable over Maliga (US5877402A) and Zhou (2007) as applied claim1, in view of Lutz (Kerry Ann Lutz et. a., Plant Physiology (2007)145(4):1201-10).
Claim 1 as the teaching of Maliga and Zhou is discussed above.
Claims 2, 7, and 10 are interpreted as depending of claim 1.
Claim 2 recites the vector of claim 1, wherein (a) the first flanking sequence comprises trnI as species election, and (b) the second flanking sequence comprises trnA as species election.
Maliga teaches plastid transformation construct comprising plastid flaking sequence for homologous recombination into the plastid genome (claim 1 and 3). Maliga does not teach trnI as first flanking sequence and trnA as second franking sequence.
Lutz teaches plastid vector targeting insertion in the trnI-trnA region (page 1201, Abstract). It would have been obvious for a person having ordinary skill in the art to use the known trnI and trnA flanking sequences in the plastid construct of Maliga as a known plastid insertion site for targeted plastid integration.
Accordingly, claim 2 is obvious over Maliga in view of Zhou and Lutz.
Claim 7 recites the vector of claim 1, wherein the regulatory sequence comprises a promoter operative in the plastid genome, and wherein: a) the promoter is selected from psbA gene as species election.
Lutz teaches use of plastid psbA promoter in plastid expression cassettes (page 1202, right collum paragraph 3, and page 1205 Table 1).
It would have been obvious to use the known plastid psbA promoter in the plastid construct of Maliga for plastid expression of the heterologous coding sequence. Accordingly, claim 7 is obvious over Maliga in view of Zhou and Lutz.
Claim 10 recites the vector of claim 1, wherein the regulatory sequence further comprises:(a) a 5' untranslated region (UTR) capable of providing transcription and translation enhancement of the heterologous polynucleotide coding for the protein of interest, wherein the 5' UTR is (i) a 5' UTR of T7G10 as species election; (b) a 3' UTR capable of conferring stability to a transcript of the protein of interest, wherein the 3' UTR is (i) a 3' UTR of psbA gene.
Maliga teaches plastid 5’regulateory segments and plastid 3’regulatory segments for promoting expression and mRNA stability in plastids (claim 1bii and 1biii), and Lutz teaches the T7 gene 10 leader for high-level translation in chloroplasts (page 1206, left column paragraph 1) and plastid 3’UTR regulatory elements including psbA (page 1202, right column, paragraph 3; page 1205, Table 1).
It would have been obvious to select the know T7G10 5’UTR and psbA 3’UTR as expression-control elements for predictable enhancement of plastid expression. Accordingly, claim 10 is obvious over Maliga in view of Zhou and Lutz.
Claims 29, 45 and 53 are rejected under 35 U.S.C. §103 as being unpatentable over Maliga (US5877402A) and Zhou (2007) as applied claim1, in view of Daniell (Henry Daniell, WO2001072959A2, Application: 2001-02-28, Publication: 2001-10-04).
Claim 1 as the teaching of Maliga and Zhou is discussed above.
Claims 29 and 45 are interpreted as dependent of claim 1.
Claim 29 recites the vector of claim 1, wherein the protein of interest is (b) expressed in an amount of about 0.1% to about 60% of total soluble protein (TSP) as species election.
Daniell teaches high-level accumulation of heterologous proteins in chloroplast, including about 7% of the total soluble protein of human somatotropin (page 111, line 6), 46.1% of the total soluble plant protein of Bt Cry2Aa2 operon (page 111, line 28). Daniell further teaches different construct modification to optimization of gene expression and protein production (page 114-123).
It would have been obvious to optimize plastid expression within the claimed rage of about 0.1% to about 60% TSP using known expression control element. Claim 29 is obvious over Maliga and in view of Zhou and Daniell.
Claim 45 recites a plant plastid, plant cell or plant stably transformed with the transformation vector of claim 1, wherein: (c) the protein of interest is present in the plastid as a monomer, a dimer, a trimer or additional forms of multimers in amount of about 0.1% TSP to about 60% TSP as species election.
Daniell further teaches isolation of monomer fraction of HSA protein with Chromatographic techniques (page 89, line 24-27). Daniel further teaches, chloroplast expressed CTB protein shows CTB monomers predominantly, with some protein in the dimeric and trimeric form (page 58, line 1-14). It would have been obvious that a heterologous protein expressed in plastids may be present in monomeric, dimeric, trimeric, or multimeric forms depending on the biochemical nature of the protein. Claim 45 is obvious over Maliga and in view of Zhou and Daniell.
Claim 53 recites a progeny or seed of the plant of claim 45.
Daniell teaches stable plastid transformation of biologically active molecule (claim 9), wherein the biologically active molecule is HAS (claim 11), and “a stable transformed plant which comprises plastid stably transformed with the vector of claims 11, or the progeny or the seed thereof” (claim 12). Thus, progeny or seed of the transformed plant would have been taught.
Claim 53 is obvious over Maliga and in view of Zhou and Daniell.
Claim 16 is rejected under 35 U.S.C. §103 as being unpatentable over Maliga (US5877402A) and Zhou (2007) as applied claim1, in view of Yarbakht (Melina Yarbakht et. al., Biotechnology and Applied Biochemistry (2015)62(1):55-63).
Claim 1 as the teaching of Maliga and Zhou is discussed above.
Claim 16 is interpreted as dependent of claim 1.
Claim 16 recites the vector of claim 1, wherein: (c) the protein of interest is Staphylococcus aureus Protein A as species election.
Maliga teaches a plastid/chloroplast transformation vector for expression of foreign proteins in plants (claim 1), and Maliga further teaches that plastids of higher plants are highly polyploid and present in many copies per cell, e.g., about 10,000 plastid genome copies per tobacco cell (column 43, line 40), making the plastid genome an attractive target for engineering because it provide readily obtainable high protein levels and permits high-level expression of recombinant proteins (column 57, line47-50).
Yarbakht teaches bicistronic expression of a human proinsulin-Protein A fusion in tobacco chloroplast, i.e., expression of a construct containing Staphylococcus aureus Protein A in the tobacco chloroplast genome( page 55, Abstract; page 56, left column, paragraph 3).
It would have been obvious to one of ordinary skill in the art at the time of the invention to select Staphylococcus aureus Protein A as the recited “protein of interest” in the plastid vector of Maliga because Yarbakht expressly teaches that Protein A can be expressed from the tobacco chloroplast, and Maliga teaches that plastid transformation in higher plants provide high-level expression due to the presence of multiple plastid genomes in each cell.
For the same reason set forth for claim 1, Zhou teaches the recited 50-bp psbN/psbH-region spacer incorporated into a plastid expression construct. Therefore, claim 16 is unpatentable over Maliga in view of Zhou and Yarbakht.
Claim 18 is rejected under 35 U.S.C. §103 as being unpatentable over Maliga (US5877402A) and Zhou (2007), in view of Yarbakht (2015) as applied claim 16, and further in view of Daniell (WO2001072959A2).
Claim 16 as the teaching of Maliga, Zhou and Yarbakht is discussed above.
Claim 18 is interpreted as dependent of claim 16.
Claims 18 recites the vector of claim 16, wherein the plastid is from a dicot plant and wherein the dicot plant is a low-nicotine tobacco plant as species election.
For the same reason set forth as for claim 16, Maliga in view of Zhou and Yarbakht teaches the vector of claim 16.
Daniell teaches plastid transformation in tobacco (claim 15), Daniell further teaches to use nicotine free edible tobacco to produce target protein (page 8, line 5-9). Such that the recited dicot low-nicotine plastid is taught.
Claim 18 is unpatentable over Maliga and Zhou in view of Yarbakht and Daniell.
Response to Applicant’s Remarks:
Applicants’ arguments regarding the rejections under 103 have been fully considered but are not persuasive.
Applicant argues that Malig fails to teach the spacer region newly recited in claim 1, and that Lutz, Daniell, and Yarbakht do not cure this deficiency. The examiner acknowledges that Maliga does not expressly teach the recited spacer limitation.
However, the rejections have been modified to further include Zhou. Zhou teaches a 50-bp intercistronic expression element form the psbT-psbH spacer region, wherein the relevant portion is between the antisense psbN sequence and psbH (Figure 1(b); Figures 1 and 2; Table 1), and demonstrates its use in a plastid transformation construct. It would have been obvious to incorporate the spacer taught by Zhou into the plastid expression cassette of Maliga to facilitate RNA processing and stable accumulation of downstream transcripts.
Accordingly, Zhou remedies the deficiency identified by Applicant. Lutz, Daniell, and Yarbakht continue to teach the respective additional imitations of claims 2, 7, 10, 16, 18, 29, 45, and 53 for the same reasons set forth in the rejections above.
With respect to amended claim 4, Maliga teaches plastid flanking sequences that mediate homologous recombination, and sequence comparison demonstrates approximately 99% identity to a corresponding Nicotiana plastid genomic sequence, thereby meeting the claimed at least 95% sequence identity limitation.
Accordingly, Applicant’s arguments do not overcome the rejections of claims 1, 2, 7, 10, 16, 18, 29, 45, and 53.
PNG
media_image1.png
860
1644
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Greyscale
Nicotiana alata genome assembly, organelle: plastid:chloroplast
Sequence ID: OZ539903.1Length: 155933Number of Matches: 2
Range 1: 101332 to 104272GenBankGraphicsNext MatchPrevious Match
Alignment statistics for match #1
Score
Expect
Identities
Gaps
Strand
5312 bits(2876)
0.0
2939/2964(99%)
25/2964(0%)
Plus/Minus
Query 1 AATTCACCGCCGTATGGCTGACCGGCGATTACTAGCGATTCCGGCTTCATGCAGGCGAGT 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 104272 AATTCACCGCCGTATGGCTGACCGGCGATTACTAGCGATTCCGGCTTCATGCAGGCGAGT 104213
Query 61 TGCAGCCTGCAATCCGAACTGAGGACGGGTTTTTGGGGTTAGCTCACC-TCGCGGGATCG 119
|||||||||||||||||||||||||||||||||||||||||||||||| |||||||||||
Sbjct 104212 TGCAGCCTGCAATCCGAACTGAGGACGGGTTTTTGGGGTTAGCTCACCCTCGCGGGATCG 104153
Query 120 CGACCCTTTGTCCCGGCCATTGTAGCACGTGTGTCGCCCAGGGCATAAGGGGCATGATGA 179
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 104152 CGACCCTTTGTCCCGGCCATTGTAGCACGTGTGTCGCCCAGGGCATAAGGGGCATGATGA 104093
Query 180 CTTGACGTCATCCTCACCTTCCTCCGGCTTATCACCGGCAGTCTGTTCAGGGTTCCAAAC 239
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 104092 CTTGACGTCATCCTCACCTTCCTCCGGCTTATCACCGGCAGTCTGTTCAGGGTTCCAAAC 104033
Query 240 TCAACGATGGCAACTAAACACGAGGGTTGCGCTCGTTGCGGGACTTAACCCAACACCTTA 299
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 104032 TCAACGATGGCAACTAAACACGAGGGTTGCGCTCGTTGCGGGACTTAACCCAACACCTTA 103973
Query 300 CGGCACGAGCTGACGACAGCCATGCACCACCTGTGTCCGCGTTCCCGAAGGCACCCCTCT 359
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 103972 CGGCACGAGCTGACGACAGCCATGCACCACCTGTGTCCGCGTTCCCGAAGGCACCCCTCT 103913
Query 360 CTTTCAAGAGGATTCGCGGCATGTCAAGCCCTGGTAAGGTTCTTCGCTTTGCATCGAATT 419
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 103912 CTTTCAAGAGGATTCGCGGCATGTCAAGCCCTGGTAAGGTTCTTCGCTTTGCATCGAATT 103853
Query 420 AAACCACATGCTCCACCGCTTGTGCGGGCCCCCGTCAATTCCTTTGAGTTTCATTCTTGC 479
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 103852 AAACCACATGCTCCACCGCTTGTGCGGGCCCCCGTCAATTCCTTTGAGTTTCATTCTTGC 103793
Query 480 GAACGTACTCCCCAGGCGGGATACTTAACGCGTTAGCTACAGCACTGCACGGGTCGATAC 539
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 103792 GAACGTACTCCCCAGGCGGGATACTTAACGCGTTAGCTACAGCACTGCACGGGTCGATAC 103733
Query 540 GCACAGCGCCTAGTATCCATCGTTTACGGCTAGGACTACTGGGGTATCTAATCCCATTCG 599
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 103732 GCACAGCGCCTAGTATCCATCGTTTACGGCTAGGACTACTGGGGTATCTAATCCCATTCG 103673
Query 600 CTCCCCTAGCTTTCGTCTCTCAGTGTCAGTGTCGGCCCAGCAGAGTGCTTTCGCCGTTGG 659
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 103672 CTCCCCTAGCTTTCGTCTCTCAGTGTCAGTGTCGGCCCAGCAGAGTGCTTTCGCCGTTGG 103613
Query 660 TGTTCTTTCCGATCTCTACGCATTTCACCGCTCCACCGGAAATTCCCTCTGCCCCTACCG 719
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 103612 TGTTCTTTCCGATCTCTACGCATTTCACCGCTCCACCGGAAATTCCCTCTGCCCCTACCG 103553
Query 720 TACTCCAGCTTGGTAGTTTCCACCGCCTGTCCAGGGTTGAGCCCTGGGATTTGACGGCGG 779
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 103552 TACTCCAGCTTGGTAGTTTCCACCGCCTGTCCAGGGTTGAGCCCTGGGATTTGACGGCGG 103493
Query 780 ACTTAAAAAGCCACCTACAGACGCTTTACGCCCAATCATTCCGGATAACGCTTGCATCCT 839
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 103492 ACTTAAAAAGCCACCTACAGACGCTTTACGCCCAATCATTCCGGATAACGCTTGCATCCT 103433
Query 840 CTGTATTACCGCGGCTGCTGGCACAGAGTTAGCCGATGCTTATTCCCCAGATACCGTCAT 899
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 103432 CTGTATTACCGCGGCTGCTGGCACAGAGTTAGCCGATGCTTATTCCCCAGATACCGTCAT 103373
Query 900 TGCTTCTTCTCCGGGAAAAGAAGTTCACGACCCGTGGGCCTTCTACCTCCACGCGGCATT 959
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 103372 TGCTTCTTCTCCGGGAAAAGAAGTTCACGACCCGTGGGCCTTCTACCTCCACGCGGCATT 103313
Query 960 GCTCCGTCAG-CTTTCGCCCATTGCGGAAAATTCCCCACTGCTGCCTCCCGTAGGAGTCT 1018
|||||||||| |||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 103312 GCTCCGTCAGGCTTTCGCCCATTGCGGAAAATTCCCCACTGCTGCCTCCCGTAGGAGTCT 103253
Query 1019 GGGCCGTGTCTCAGTCCCAGTGTGGCTGATCATCCTCTCGGACCAGCTACTGATCATCGC 1078
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 103252 GGGCCGTGTCTCAGTCCCAGTGTGGCTGATCATCCTCTCGGACCAGCTACTGATCATCGC 103193
Query 1079 CTTGGTAAGCTATTGCCTCACCAACTAGCTAATCAGACGCGAGCCCCTCCTCGGGCGGAT 1138
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 103192 CTTGGTAAGCTATTGCCTCACCAACTAGCTAATCAGACGCGAGCCCCTCCTCGGGCGGAT 103133
Query 1139 TCCTCCTTTTGCTCCTCAGCCTACGGGGTATTAGCAGCCGTTTCCAGCTGTTGTTCCCCT 1198
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 103132 TCCTCCTTTTGCTCCTCAGCCTACGGGGTATTAGCAGCCGTTTCCAGCTGTTGTTCCCCT 103073
Query 1199 CCCAAGGGCAGGTTCTTACGCGTTACTCACCCGTCCGCCACTGGAAACACCACTTCCCGT 1258
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 103072 CCCAAGGGCAGGTTCTTACGCGTTACTCACCCGTCCGCCACTGGAAACACCACTTCCCGT 103013
Query 1259 CCGACTTGCATGTGTTAAGCATGCCGCCAGCGTTCATCCTGAGCCAGGATCGAACTCTCC 1318
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 103012 CCGACTTGCATGTGTTAAGCATGCCGCCAGCGTTCATCCTGAGCCAGGATCGAACTCTCC 102953
Query 1319 ATGAGATTCATAGTTGCATTACTTATAGCTTCCTTGTTCGTAGACAAAGCGGATTCGGAA 1378
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 102952 ATGAGATTCATAGTTGCATTACTTATAGCTTCCTTGTTCGTAGACAAAGCGGATTCGGAA 102893
Query 1379 TTGTCTTTCATTCCAAGGCATAACTTGTATCCATGCGCTTCATATTCGCCCGGAGTTCGC 1438
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 102892 TTGTCTTTCATTCCAAGGCATAACTTGTATCCATGCGCTTCATATTCGCCCGGAGTTCGC 102833
Query 1439 TCCCAGAAATATAGCCATCCCTGCCCCCTCACGTCAATCCCACGAGCCTCTTATCCATTC 1498
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 102832 TCCCAGAAATATAGCCATCCCTGCCCCCTCACGTCAATCCCACGAGCCTCTTATCCATTC 102773
Query 1499 TCATTGAACGACGGCGGGGGAGCTTTCGAGGCCTCGAAATCCAACTAGAAAAACTCACAT 1558
||||||||||||||||||||||| ||||||||||||||||||||||||
Sbjct 102772 TCATTGAACGACGGCGGGGGAGC-------------AAATCCAACTAGAAAAACTCACAT 102726
Query 1559 TGGGCTTAGGGATAATCAGGCTCGAACTGATGACTTCCACCACGTCAAGGTGACACTCTA 1618
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 102725 TGGGCTTAGGGATAATCAGGCTCGAACTGATGACTTCCACCACGTCAAGGTGACACTCTA 102666
Query 1619 CCGCTGAGTTATATCCCTTCCCCGCCCCATCGAGAAATAGAACTGACTAATCCTAAGTCA 1678
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 102665 CCGCTGAGTTATATCCCTTCCCCGCCCCATCGAGAAATAGAACTGACTAATCCTAAGTCA 102606
Query 1679 AAGGGTCGAGAAACTCAACGCCACTATTCTTGAACAACTTGGAGCCGGGCCTTCTTTTCG 1738
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 102605 AAGGGTCGAGAAACTCAACGCCACTATTCTTGAACAACTTGGAGCCGGGCCTTCTTTTCG 102546
Query 1739 CACTATTACGGATATGAAAATAATGGTCAAAATCGGATTCAATTGTCAAAGTACTTTAAC 1798
||||||||||||||||||||||||||||||||||||||||||||||||| |
Sbjct 102545 CACTATTACGGATATGAAAATAATGGTCAAAATCGGATTCAATTGTCAA----------C 102496
Query 1799 TGCCCCTATCGGAAATAGGATTGACTACCGATTCCGAAGGAACTGGAGTTACATCTCTTT 1858
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 102495 TGCCCCTATCGGAAATAGGATTGACTACCGATTCCGAAGGAACTGGAGTTACATCTCTTT 102436
Query 1859 TCCATTCAAGAGTTCTTATGCGTTTCCACGCCCCTTTGAGACCCCGAAAAATGGACAAAT 1918
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 102435 TCCATTCAAGAGTTCTTATGCGTTTCCACGCCCCTTTGAGACCCCGAAAAATGGACAAAT 102376
Query 1919 TCCTTTTCTTAGGAACACATACAAGATTCGTCACTACAAAAAGGATAATGGTAACCCTAC 1978
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 102375 TCCTTTTCTTAGGAACACATACAAGATTCGTCACTACAAAAAGGATAATGGTAACCCTAC 102316
Query 1979 CATTAACTACTTCATTTATGAATTTCATAGTAATAGAAATACATGTCCTACCGAGACAGA 2038
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 102315 CATTAACTACTTCATTTATGAATTTCATAGTAATAGAAATACATGTCCTACCGAGACAGA 102256
Query 2039 ATTTGGAACTTGCTATCCTCTTGCCTAGCAGGCAAAGATTTACCTCCGTGGAAAGGATGA 2098
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 102255 ATTTGGAACTTGCTATCCTCTTGCCTAGCAGGCAAAGATTTACCTCCGTGGAAAGGATGA 102196
Query 2099 TTCATTCGGATCGACATGAGAGTCCAACTACATTGCCAGAATCCATGTTGTATATTTGAA 2158
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 102195 TTCATTCGGATCGACATGAGAGTCCAACTACATTGCCAGAATCCATGTTGTATATTTGAA 102136
Query 2159 AGAGGTTGACCTCCTTGCTTCTCTCATGGTACACTCCTCTTCCCGCCGAGCCCCTTTTCT 2218
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 102135 AGAGGTTGACCTCCTTGCTTCTCTCATGGTACACTCCTCTTCCCGCCGAGCCCCTTTTCT 102076
Query 2219 CCTCGGTCCACAGAGACAAAATGTAGGACTGGTGCCAACAATTCATCAGACTCACTAAGT 2278
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 102075 CCTCGGTCCACAGAGACAAAATGTAGGACTGGTGCCAACAATTCATCAGACTCACTAAGT 102016
Query 2279 CGGGATCactaactaatactaatctaatataatagtctaatatatctaatataatagaaa 2338
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 102015 CGGGATCACTAACTAATACTAATCTAATATAATAGTCTAATATATCTAATATAATAGAAA 101956
Query 2339 atactaatataataGAAAAGAACTGTCTTTTCTGTATACTTTCCCCGGTTCCGTTGCTAC 2398
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 101955 ATACTAATATAATAGAAAAGAACTGTCTTTTCTGTATACTTTCCCCGGTTCCGTTGCTAC 101896
Query 2399 CGCGGGCTTTACGCAATCGATCGGATTAGATAGATATCCCTTCAACATAGGTCATCGAAA 2458
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 101895 CGCGGGCTTTACGCAATCGATCGGATTAGATAGATATCCCTTCAACATAGGTCATCGAAA 101836
Query 2459 GGATCTCGGAGACCCACCAAAGTACGAAAGCCAGGATCTTTCAGAAAACGGATTCCTATT 2518
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 101835 GGATCTCGGAGACCCACCAAAGTACGAAAGCCAGGATCTTTCAGAAAACGGATTCCTATT 101776
Query 2519 CAAAGAGTGCATAACCGCATGGATAAGCTCACACTAACCCGTCAATTTGGGATCCAAATT 2578
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 101775 CAAAGAGTGCATAACCGCATGGATAAGCTCACACTAACCCGTCAATTTGGGATCCAAATT 101716
Query 2579 CGAGATTTTCCTTGGGAGGTATCGGGAAGGATTTGGAATGGAATAATATCGATTCATACA 2638
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 101715 CGAGATTTTCCTTGGGAGGTATCGGGAAGGATTTGGAATGGAATAATATCGATTCATACA 101656
Query 2639 GAAGAAAAGGTTCTCTATTGATTCAAACACTGTACCTAACCTATGGGATAGGGATCGAGG 2698
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 101655 GAAGAAAAGGTTCTCTATTGATTCAAACACTGTACCTAACCTATGGGATAGGGATCGAGG 101596
Query 2699 AAGGGGAAAAACCGAAGATTTCACATGGTACTTTTATCAATCTGATTTATTTCGTACCTT 2758
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 101595 AAGGGGAAAAACCGAAGATTTCACATGGTACTTTTATCAATCTGATTTATTTCGTACCTT 101536
Query 2759 TCGTTCAATGAGAAAATGGGTCAAATTCTACAGGATCAAACCTATGGGACTTAAGGAATG 2818
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 101535 TCGTTCAATGAGAAAATGGGTCAAATTCTACAGGATCAAACCTATGGGACTTAAGGAATG 101476
Query 2819 ATATaaaaaaaaGAGAGGGAAAATATTCATATTAAATAAATATGAAGTAGAAGAACCCAG 2878
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 101475 ATATAAAAAAAAGAGAGGGAAAATATTCATATTAAATAAATATGAAGTAGAAGAACCCAG 101416
Query 2879 ATTCCAAATGAACAAATTCAAACTTGAAAAGGATCTTCCTTATTCTTGAAGAATGAGGGG 2938
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 101415 ATTCCAAATGAACAAATTCAAACTTGAAAAGGATCTTCCTTATTCTTGAAGAATGAGGGG 101356
Query 2939 CAAAGGGATTGATCAAGAAAGATC 2962
||||||||||||||||||||||||
Sbjct 101355 CAAAGGGATTGATCAAGAAAGATC 101332
Conclusion
No claims are allowed.
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 YANXIN SHEN whose telephone number is (571)272-7538. The examiner can normally be reached Monday-Friday.
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/YANXIN SHEN/Examiner, Art Unit 1663
/WEIHUA FAN/Primary Examiner, Art Unit 1663