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 .
1. Original claims 1-21 are pending and under examination.
Claim Objections
2. Claim 1 should be rewritten as follows:
A method for selectively transducing target cells, wherein the method comprises contacting a pseudotyped retrovirus-like particle or retroviral vector with target cells, wherein the pseudotyped retrovirus-like particle or retroviral vector comprises:
a) at least one cell targeting fusion protein comprising (i) a truncated Nipah virus envelope glycoprotein G lacking amino acids 2-34 of SEQ ID NO: 9 (GcA34) and (ii) at least one cell targeting domain; and
b) at least one truncated Nipah virus envelope glycoprotein F lacking amino acids 525-546 of SEQ ID NO:11 (FcA22).
3. Claim 2 should be rewritten as follows:
The method of claim 1, wherein the truncated envelope glycoprotein G of the Nipah virus comprises one or more point mutations selected from the group consisting of E501A, W504A, Q530A, and E533A.
4. Claim 3 should be rewritten as follows:
A method for selectively transducing target cells, wherein the method comprises contacting the target cells with a pseudotyped retrovirus-like particle or retroviral vector with, wherein the pseudotyped retrovirus-like particle or retroviral vector comprises:
a) at least one cell targeting fusion protein comprising (i) a truncated Nipah virus envelope glycoprotein G lacking at least one part of the cytoplasmic region and having at least 80% sequence identity to SEQ ID NO: 9 and (ii) at least one cell targeting domain;
b) at least one truncated Nipah virus envelope glycoprotein F lacking at least one part of the cytoplasmic region and having at least 80% sequence identity to SEQ ID NO:11; and
(c) a nucleic acid encoding a chimeric antigen receptor.
5. Claim 4 should recite “the truncated Nipah virus envelope glycoprotein G”.
6. Claim 5 should be rewritten as follows:
The method of claim 4, wherein the truncated Nipah virus envelope glycoprotein G comprises one or more point mutations selected from the group consisting of E501A, W504A, Q530A, and E533A.
7. Claim 6 should recite “the truncated Nipah virus envelope glycoprotein F”.
8. Claim 7 should be rewritten as follows:
The method of claim 3, wherein:
the Nipah virus envelope glycoprotein G lacks amino acids 2-34 of SEQ ID NO: 9 (GcA34) and comprises the point mutations E501A, W504A, Q530A, and E533A ; and the at least one envelope Nipah virus glycoprotein F a lacks amino acids 525-546 of SEQ ID NO: 11 (FcA22).
9. Claim 12 is objected to because of the recitation “and/or”. Correction to “and” is required.
10. Claim 13 is objected to because of the recitation “The method of claim 1, which comprises a gene”. Correction to “The method of claim 1, wherein the pseudotyped retrovirus-like particle or retroviral vector comprises a gene” is required.
11. Claim 15 should recite “the pseudotyped retrovirus-like particle or retroviral vector”.
12. Claim 15 is objected to because of the recitations “an envelope” and “Hof” in lined 3. Correction to “the envelope” and “H of” is required.
13. Claim 18 should be rewritten as follows:
A method of performing immune therapy in a subject, comprising administering to the subject an effective amount of a pseudotyped retrovirus-like particle or retroviral vector, wherein the pseudotyped retrovirus-like particle or retroviral vector comprises
a) at least one cell targeting fusion protein comprising (i) a truncated Nipah virus envelope glycoprotein G lacking at least one part of the cytoplasmic region and having at least 80% sequence identity to SEQ ID NO: 9 and (ii) at least one cell targeting domain;
b) at least one truncated Nipah virus envelope glycoprotein F lacking at least one part of the cytoplasmic region and having at least 80% sequence identity to SEQ ID NO:11; and
c) a chimeric antigen receptor.
14. Claim 19 should be rewritten as follows:
A method of treating a subjecting having cancer, comprising administering to the subject an effective amount of a pseudotyped retrovirus-like particle or retroviral vector, wherein the pseudotyped retrovirus-like particle or retroviral vector comprises
a) at least one cell targeting fusion protein comprising (i) a truncated Nipah virus envelope glycoprotein G lacking at least one part of the cytoplasmic region and having at least 80% sequence identity to SEQ ID NO: 9 and (ii) at least one cell targeting domain;
b) at least one truncated Nipah virus envelope glycoprotein F lacking at least one part of the cytoplasmic region and having at least 80% sequence identity to SEQ ID NO:11; and
c) a chimeric antigen receptor.
15. Claim 21 should be rewritten as follows:
A method for producing a pseudotyped retrovirus-like particle, wherein said method comprises co-transfecting a packaging cell line with:
(a) at least one nucleic acid encoding a cell targeting fusion protein comprising (i) a Nipah virus envelope glycoprotein G having a truncation in the cytoplasmic region and having at least 80% sequence identity to SEQ ID NO: 9 and (ii) at least one cell targeting domain,
(b) at least one nucleic acid encoding a modulating fusion protein, said comprising (i) either a Nipah virus envelope glycoprotein G having a truncation in the cytoplasmic region and having at least 80% sequence identity to SEQ ID NO: 9 or a transmembrane domain (ii) at least one functional domain,
(c) at least one nucleic acid encoding a truncated Nipah virus envelope glycoprotein F lacking at least one part of the cytoplasmic region and having at least 80% sequence identity to SEQ ID NO: 11, and
(d) at least one vector comprising a nucleic acid encoding core proteins from said retrovirus.
Claim Rejections - 35 USC § 103
16. 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.
17. Claims 1, 2, 8, 9, 11, and 12 are rejected under 35 U.S.C. 103 as being unpatentable over Witting et al. (Gene Therapy, 2013, 20: 997-1005), in view of both Buchholtz et al. (WO 08/037458) and Negrete et al. (J. Virol., 2007, 81: 10804-10814). Witting et al. and Negrete et al. are cited on the IDS filed on 07/17/2023.
Witting et al. teach a lentiviral particle pseudotyped with Nipah virus (NiV) attachment (G) and fusion (F) proteins having a truncated cytoplasmic tails (NiV-G[Symbol font/0x44]34 and Niv-F[Symbol font/0x44]25, respectively); the combination of NiV-G[Symbol font/0x44]34 and F Niv-F[Symbol font/0x44]25 results in high lentiviral titers. Witting et al. teach that NiV-G is responsible for binding to the NiV cellular receptors ephrin-B2 and B3. Witting et al. teach using the pseudotyped lentiviral particle for gene delivery to cells expressing ephrin-B2 and B3 (claims 1 and 8) (see Abstract; paragraph bridging p. 997 and 998; p. 998, Fig. 1-2; paragraph bridging p. 998 and 1000; p. 999, Fig. 3; p. 1002, column 2, second full paragraph).
Fig. 1 and 2 in Witting et al. show that the cytoplasmic domain of NiV-G is located at the N-terminus, while that of NiV-F is located at the C-terminus.
As shown in Fig. 1, the cytoplasmic domains of NiV-G and NiV-G[Symbol font/0x44]34 are:
NIV-G NH2-MPAENKKVRFENTTSDKGKIPSKVIKSYYGTMDIKKINEGLLDSK
NiV-G[Symbol font/0x44]34 NH2-MKKINEGLLDSK (in bold below)
Thus, NiV-G[Symbol font/0x44]34 lacks the PAENKKVRFENTTSDKGKIPSKVIKSYYGTMDI sequence, i.e., amino acids 2-34 of SEQ ID NO: 9 (underlined below) (claim 1).
Claimed SEQ ID NO: 9 (wild type NiV-G; see the attached alignment)
MPAENKKVRF ENTTSDKGKI PSKVIKSYYG TMDIKKINEG LLDSKILSAF NTVIALLGSI 60
VIIVMNIMII QNYTRSTDNQ AVIKDALQGI QQQIKGLADK IGTEIGPKVS LIDTSSTITI 120
PANIGLLGSK ISQSTASINE NVNEKCKFTL PPLKIHECNI SCPNPLPFRE YRPQTEGVSN 180
LVGLPNNICL QKTSNQILKP KLISYTLPVV GQSGTCITDP LLAMDEGYFA YSHLERIGSC 240
SRGVSKQRII GVGEVLDRGD EVPSLFMTNV WTPPNPNTVY HCSAVYNNEF YYVLCAVSTV 300
GDPILNSTYW SGSLMMTRLA VKPKSNGGGY NQHQLALRSI EKGRYDKVMP YGPSGIKQGD 360
TLYFPAVGFL VRTEFKYNDS NCPITKCQYS KPENCRLSMG IRPNSHYILR SGLLKYNLSD 420
GENPKVVFIE ISDQRLSIGS PSKIYDSLGQ PVFYQASFSW DTMIKFGDVL TVNPLVVNWR 480
NNTVISRPGQ SQCPRFNTCP EICWEGVYND AFLIDRINWI SAGVFLDSNQ TAENPVFTVF 540
KDNEILYRAQ LASEDTNAQK TITNCFLLKN KIWCISLVEI YDTGDNVIRP KLFAVKIPEQ CT 602
As shown in Fig. 2 of Witting et al., the cytoplasmic tails of NiV-F and NiV-F[Symbol font/0x44]25 are:
NiV-F EKKRNTYSRLEDRRVRPTSSGDLYYIGT-C00H
NiV-F[Symbol font/0x44]25 EKK-COOH (in bold below).
Thus, NiV-F[Symbol font/0x44]25 lacks amino acids RNTYSRLEDRRVRPTSSGD, i.e., amino acids 522-546 of SEQ ID NO: 11 (underlined below) (claim 1).
Claimed SEQ ID NO: 11 (wild type NiV-F, see the attached alignment)
MVVILDKRCY CNLLILILMI SECSVGILHY EKLSKIGLVK GVTRKYKIKS NPLTKDIVIK 60
MIPNVSNMSQ CTGSVMENYK TRLNGILTPI KGALEIYKNN THDLVGDVRL AGVIMAGVAI 120
GIATAAQITA GVALYEAMKN ADNINKLKSS IESTNEAVVK LQETAEKTVY VLTALQDYIN 180
TNLVPTIDKI SCKQTELSLD LALSKYLSDL LFVFGPNLQD PVSNSMTIQA ISQAFGGNYE 240
TLLRTLGYAT EDFDDLLESD SITGQIIYVD LSSYYIIVRV YFPILTEIQQ AYIQELLPVS 300
FNNDNSEWIS IVPNFILVRN TLISNIEIGF CLITKRSVIC NQDYATPMTN NMRECLTGST 360
EKCPRELVVS SHVPRFALSN GVLFANCISV TCQCQTTGRA ISQSGEQTLL MIDNTTCPTA 420
VLGNVIISLG KYLGSVNYNS EGIAIGPPVF TDKVDISSQI SSMNQSLQQS KDYIKEAQRL 480
LDTVNPSLIS MLSMIILYVL SIASLCIGLI TFISFIIVEK KRNTYSRLED RRVRPTSSGD 540
LYYIGT 546
While NiV-F[Symbol font/0x44]25 is three amino acids shorter than the claimed Fv[Symbol font/0x44]22, it is noted that there is no evidence of record that the presence of extra three amino acids results in unexpected properties. As per MPEP § 716.02, [a]ny differences between the claimed invention and the prior art may be expected to result in some differences in properties. The issue is whether the properties differ to such an extent that the difference is really unexpected. In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). A difference of three amino acids is not patentably relevant if it does not provide a novel feature.
Witting et al. do not teach retargeting the retroviral particle by using a fusion between NiV-G[Symbol font/0x44]34 and a targeting ligand (claim 1). Buchholtz et al. teach that lentiviral particles pseudotyped with attachment and fusion proteins could be retargeted to transduce a cell of interest by modifying the attachment protein via: (1) fusing it with a ligand (such as an scFv) targeting the cell of interest (such as a CD4 or CD8 T-cell); and (2) mutating it such that it is not capable of interacting with its natural cellular receptor (see Abstract; paragraph bridging p. 1 and 2; p. 2, lines 12-19; p. 3, lines 14-17; paragraph bridging p. 26 and 27; p. 27, lines 4-28; p. 28; p. 33, lines 8-14). Negrete et al. teach that the mutation E533Q in NiV-G completely abrogates binding to ephrin-B2 and ephrin-B3 (see Abstract; p. 1080, column 1, second full paragraph). Based on these teachings, one of skill in the art would have found obvious to modify NiV-G[Symbol font/0x44]34 by fusing it with an scFv targeting CD4 or CD8 on T-cells and introducing the E533Q mutation, to achieve the predictable result of specifically retargeting the pseudotyped lentiviral particle to CD4 or CD8 T-cells. One of skill in the art would have also fond obvious to further administering the resultant pseudotyped lentiviral particle to T-cells to achieve the predictable result of obtaining T-cells expressing genes of interest, when obtaining T-cell expressing genes of interest was needed (claims 9, 11, and 12).
While the E533Q mutation is not exactly E533A (claim 2), as per MPEP § 716.02, [a]ny differences between the claimed invention and the prior art may be expected to result in some differences in properties. The issue is whether the properties differ to such an extent that the difference is really unexpected. In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). In this case, the E533Q mutation enables retargeting to cells of interest by abolishing binding to both ephrin-B2 and ephrin-B3. There is no evidence of record that E533A provides for more than E533Q with respect to retargeting; there is no evidence of record that E533A confers unexpected properties over E533Q. Using E533A is not patentably relevant if it does not produce a novel feature when compared to E533Q.
Thus, the claimed invention was prima facie obvious at the time of its effective filing date.
18. Claims 1-21 are rejected under 35 U.S.C. 103 as being unpatentable over Witting et al. taken with both Buchholtz et al. and Negrete et al., in further view of Hurton et al. (Blood, 2008, 112, Abstract 3035).
The teachings of Witting et al., Buchholtz et al., and Negrete et al. are applied as above for claims 1, 2, 8, 9, 11, and 12. Although the combination of Witting et al., Buchholtz et al., and Negrete et al. teaches retargeting to introduce genes of interest into to a CD4 or CD8 T-cell, the combination does not specifically teach that the genes of interest are CD19 CAR and membrane-bound IL-7 (mIL-7) (claims 3-7, 10, and 12-17). Hurton et al. teach genetically modifying T-cells with CD19 CAR and mIL-7, where IL-7 improves the survival and proliferation of CAR T-cells. Hurton et al. teach suggests evaluating the therapeutic potential of the resulting T-cells in clinical trials (see Abstract). Based on these teachings, one of skill in the art would have found obvious to modify the pseudotyped lentiviral particles by using a nucleic acid encoding the CD19 CAR and a nucleic acid encoding the mIL-7 as the genes of interest to achieve the predictable result of obtaining a composition suitable for cancer therapy. One of skill in the art would have found obvious to further administer the T-cells expressing CD19 CAR and mIL-7 to subjects affected by CD19-expressing cancers with the reasonable expectation that doing so would treat the cancer in these subjects. By doing so, one of skill in the art would have practiced the methods of claims 18-20.
With respect to claim 7, the cited prior art does not teach all of E501A, W504A, Q530A, and E533A. However, the cited prior art teaches E533Q which completely abrogates binding to both ephrin-B2 and ephrin-B3 (see above). There is no evidence of record that E501A, W504A, Q530A, and E533A together provide for more than E533Q with respect to retargeting; there is no evidence of record that using E501A, W504A, Q530A, and E533A together confers unexpected properties over using E533Q, which completely abrogates binding to ephrin-B2 and ephrin-B3. Specifically using E501A, W504A, Q530A, and E533A instead of E533Q is not patentably relevant if it does not confer unexpected properties. As per MPEP § 716.02, [a]ny differences between the claimed invention and the prior art may be expected to result in some differences in properties. The issue is whether the properties differ to such an extent that the difference is really unexpected. In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
With respect to claim 21, Buchholtz et al. teach obtaining the pseudotyped lentivirus by co-transfecting HEK293 cells with a packaging plasmid encoding the lentiviral GAG and POL (i.e., core proteins), a plasmid encoding the fusion scFv-attachment protein, a plasmid encoding the F proteins, and a transfer plasmid encoding a gene of interest (see p. 66, lines 20-25). One of skill in the art would have found obvious to obtain the pseudotyped lentiviral particles by co-transfecting the HEK293 cells with a packaging plasmid, a plasmid encoding the fusion of CD4/CD8 scFv/NiV-G[Symbol font/0x44]34, a plasmid encoding NiV-F[Symbol font/0x44]25, a plasmid encoding the CD19 CAR, and a transfer plasmid encoding mIL-7.
Thus, the claimed invention was prima facie obvious at the time of its effective filing date.
19. No claim is allowed. No claim is free of prior art.
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/ILEANA POPA/Primary Examiner, Art Unit 1633