DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
Claims 1-42 have been canceled. Claims 43-62 remain pending.
Applicant's arguments filed 9-10-25 have been fully considered but they are not persuasive.
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Election/Restrictions
Applicants elected Group II, claims 43-62, without traverse in the reply filed on 1-23-25. Upon review of the parent applications, specifically 13750664, now US Patent 9352028, a kit comprising RNA and the method of using the kit were examined and allowed together in US Patent 9352028. The restriction requirement was withdrawn.
Claims 43-62 remain under consideration.
Claim objections
The term “subject” in the phrase “mammalian subject” in claim 43 is redundant. Just say ---mammal---.
Use of “administering” as the active step in line 3 of claim 43 while adding “the compositing is administered by injection” at the end of claim 43 is confusing. Just say ---injecting--- instead of “administering”.
Use of “immunostimulatory composition” in line 3 of claim 43 while “stimulating an anti-tumor immune response in the preamble is confusing. An “immunostimulatory” composition does not necessarily have an antitumor effect. To further confuse the matter, the body of claim 43 never results in the injection having any function, e.g. stimulating an antitumor response or decreasing the size of the tumor that expresses NYESO1 and MAGE3A. The body of claim 43 should clearly set forth injection of the composition causes an antitumor immune response as required in the preamble.
Claim 43 can be written more clearly as ---A method of stimulating an antitumor response in a mammal, the method comprising:
injecting a composition into a mammal that has a tumor expressing NYESO1 and MAGE3A such that an antitumor response is stimulated in the mammal, wherein the composition comprises:
i) isolated RNA encoding an NYESO1 antigen, wherein the RNA is at least 75% identical to the nucleic acid sequence of SEQ ID NO: 21 and comprises a 5’ cap and a polyA sequence that is 10-200 nucleotides in length; and
ii) isolated RNA encoding a MAGE3A antigen and comprising a 5’ cap and a polyA sequence that is 10-200 nucleotides in length.
Claim Rejections - 35 USC § 112
Written Description
Claims 43-62 remain rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
A) The specification lacks written description for administering a composition comprising RNAs encoding NYESO1 and MAGEA3 antigens to a mammal that has tumor expressing NYESO1 and MAGE3A without obtaining an antitumor immune response as broadly encompassed by claim 43.
This rejection assumes lung tumors that express NYESO1 and MAGE3A were well-known in the art at the time of filing. If it is found that tumors that express NYESO1 and MAGE3A were unknown and applicants did not teach tumors that express NYESO1 and MAGE3A, then another rejection will be required.
Claim 43 is drawn to “A method of stimulating an anti-tumor immune response in a mammalian subject with a tumor that expresses NYESO1 and MAGE3A, the method comprising administering an effective amount of an immunostimulatory composition of
The preamble of claim 43 encompasses treating a mammal that has any tumor that expresses NYESO1 and MAGE3A. Claim 43 requires an active step of administering a first RNA encoding an NY-ESO1 antigen, wherein the first RNA is at least about 75% identical to the nucleic acid sequence of SEQ ID NO: 21 and a second RNA encoding an MAGE-A3 antigen. However, the active step of “administering” in claim 43 does not have any functional language, and the body of the claim does not require tumor size decreases or any therapeutic result occurs. Therefore, the purpose in the preamble is merely an intended use and does not necessarily occur.
Chen (PNAS, 1997, Vol. 94, pg 1914-1918) taught NYESO1 was expressed in human cancers.
Jager (PNAS, 2006, Vol. 103, No. 39, pg 14453-14458) used vectors encoding NYESO1 to induce an immune response in mammals with a tumor.
Davis (PNAS, 2004, Vol. 101, No. 29, pg 10697-10702) administered NYESO1 with ISCOMATRIX to induce an immune response in mammals with a tumor.
Jager (PNAS, 2000, Vol. 97, No. 22, pg 12198-12203) administered NYESO1 to induce an immune response in mammals with a tumor but did not teach the sequence was 85% identical to SEQ ID NO: 21 as required in claims 51, 52.
Odunsi (PNAS, 2007, Vol. 104, No. 31, pg 12837-12842) administered NYESO1 to induce an immune response in mammals with a tumor.
Gillespie (Cancer Treatment Reviews, 1999, Vol. 25, pg 219-227), Seinel (European J. Cardio-Thoracic Surg., 2004, Vol. 25, No. 1, pg 131-134), and Atanackovic (J. Immunol., March 2004, Vol. 172, No. 5, pg 3289-3296) administered MAGE-A3 to obtain an immune response against various tumors in a mammal.
The Examples in the specification are limited to administering RNA to a mammal with a tumor such that an anti-tumor immune response is obtained (pg 77-83).
The specification does not correlate administering RNAs encoding NYESO1 and MAGEA3 antigens to a mammal that has a tumor NYESO1 and MAGEA3 such that an antitumor immune response is obtained to administering the RNAs without obtaining an antitumor immune response as broadly encompassed by claim 43.
Accordingly, the specification lacks written description for administering RNAs encoding NYESO1 and MAGEA3 antigens to a mammal that has a tumor NYESO1 and MAGEA3 such that an antitumor immune response is obtained to administering the RNAs without obtaining an antitumor immune response as broadly encompassed by claim 43.
Response to arguments
Applicants argue the amendment overcomes the rejection. Applicants’ argument is not persuasive because the amendment does not even begin to address the rejection.
B) The specification does not provide written description for using a nucleic acid sequence that is 75%, 85%, 90%, 100% identical to SEQ ID NO: 21 to obtain an immune response that is “anti” any tumor that expresses any NYESO1 as broadly encompassed by claims 43, 51, 52.
Chen (PNAS, 1997, Vol. 94, pg 1914-1918) taught NYESO1 was expressed in human cancers but did not teach the sequence was 75%, 85%, 90%, 100% identical to SEQ ID NO: 21 as broadly encompassed by claims 43, 51, 52.
Jager (PNAS, 2006, Vol. 103, No. 39, pg 14453-14458) used vectors encoding NYESO1 to induce an immune response in mammals with a tumor but did not teach the sequence was 75%, 85%, 90%, 100% identical to SEQ ID NO: 21 as broadly encompassed by claims 43, 51, 52.
Davis (PNAS, 2004, Vol. 101, No. 29, pg 10697-10702) administered NYESO1 with ISCOMATRIX to induce an immune response in mammals with a tumor but did not teach the sequence was 75%, 85%, 90%, 100% identical to SEQ ID NO: 21 as broadly encompassed by claims 43, 51, 52.
Jager (PNAS, 2000, Vol. 97, No. 22, pg 12198-12203) administered NYESO1 to induce an immune response in mammals with a tumor but did not teach the sequence was 75%, 85%, 90%, 100% identical to SEQ ID NO: 21 as broadly encompassed by claims 43, 51, 52.
Odunsi (PNAS, 2007, Vol. 104, No. 31, pg 12837-12842) administered NYESO1 to induce an immune response in mammals with a tumor but did not teach the sequence was 75%, 85%, 90%, 100% identical to SEQ ID NO: 21 as broadly encompassed by claims 43, 51, 52.
The specification says “In the context of this invention “NY-ESO-1” is cancer/testis antigen 1B and the preferred sequence of the RNA, preferably of the mRNA, encoding “NY-ESO-1" - if being used in the active (immunostimulatory) composition according to the invention - is shown in Fig. 20 (SEQ ID NO: 20), and — even more preferably — in Fig. 21 (SEQ ID NO: 21)” (pg 15, line 6; pg 16, lines 16-22).
SEQ ID NO: 21 encodes:
MQAEGRGTGGSTGDADGPGGPGIPDGPGGNAGGPGEAGATGGRGPRGAGAARASGPGGGAPRGPHGGAASGLNGCCRCGARGPESRLLEFYLAMPFATPMEAELARRSLAQDAPPLPVPGVLLKEFTVSGNILTIRLTAADHRQLQLSISSCLQQLSLLMWITQCFLPVFLAQPPSGQRR-
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278
1546
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614
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Chen says the sequence reported is in GenBank as U87459.
Human autoimmunogenic cancer/testis antigen NY-ESO-1 mRNA, complete cds
GenBank: U87459.1
FASTA Graphics
Go to:
LOCUS HSU87459 752 bp mRNA linear PRI 22-DEC-1999
DEFINITION Human autoimmunogenic cancer/testis antigen NY-ESO-1 mRNA, complete
cds.
ACCESSION U87459
VERSION U87459.1
KEYWORDS .
SOURCE Homo sapiens (human)
ORGANISM Homo sapiens
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
Catarrhini; Hominidae; Homo.
REFERENCE 1 (bases 1 to 752)
AUTHORS Chen,Y.T., Scanlan,M.J., Sahin,U., Tureci,O., Gure,A.O., Tsang,S.,
Williamson,B., Stockert,E., Pfreundschuh,M. and Old,L.J.
TITLE A testicular antigen aberrantly expressed in human cancers detected
by autologous antibody screening
JOURNAL Proc. Natl. Acad. Sci. U.S.A. 94 (5), 1914-1918 (1997)
PUBMED 9050879
REFERENCE 2 (bases 1 to 752)
AUTHORS Chen,Y.-T.
TITLE Direct Submission
JOURNAL Submitted (28-JAN-1997) Ludwig Institute for Cancer Research, New
York Branch, 1275 York Avenue, New York, NY 10021, USA
FEATURES Location/Qualifiers
source 1..752
/organism="Homo sapiens"
/mol_type="mRNA"
/db_xref="taxon:9606"
/clone_lib="esophageal squamous cell carcinoma expression
cDNA library"
CDS 54..596
/codon_start=1
/product="autoimmunogenic cancer/testis antigen NY-ESO-1"
/protein_id="AAB49693.1"
/translation="MQAEGRGTGGSTGDADGPGGPGIPDGPGGNAGGPGEAGATGGRG
PRGAGAARASGPGGGAPRGPHGGAASGLNGCCRCGARGPESRLLEFYLAMPFATPMEA
ELARRSLAQDAPPLPVPGVLLKEFTVSGNILTIRLTAADHRQLQLSISSCLQQLSLLM
WITQCFLPVFLAQPPSGQRR"
ORIGIN
1 atcctcgtgg gccctgacct tctctctgag agccgggcag aggctccgga gccatgcagg
61 ccgaaggccg gggcacaggg ggttcgacgg gcgatgctga tggcccagga ggccctggca
121 ttcctgatgg cccagggggc aatgctggcg gcccaggaga ggcgggtgcc acgggcggca
181 gaggtccccg gggcgcaggg gcagcaaggg cctcggggcc gggaggaggc gccccgcggg
241 gtccgcatgg cggcgcggct tcagggctga atggatgctg cagatgcggg gccagggggc
301 cggagagccg cctgcttgag ttctacctcg ccatgccttt cgcgacaccc atggaagcag
361 agctggcccg caggagcctg gcccaggatg ccccaccgct tcccgtgcca ggggtgcttc
421 tgaaggagtt cactgtgtcc ggcaacatac tgactatccg actgactgct gcagaccacc
481 gccaactgca gctctccatc agctcctgtc tccagcagct ttccctgttg atgtggatca
541 cgcagtgctt tctgcccgtg tttttggctc agcctccctc agggcagagg cgctaagccc
601 agcctggcgc cccttcctag gtcatgcctc ctcccctagg gaatggtccc agcacgagtg
661 gccagttcat tgtgggggcc tgattgtttg tcgctggagg aggacggctt acatgtttgt
721 ttctgtagaa aataaaactg agctacgaaa aa
Perhaps this is the basis of the coding sequence used by applicants to arrive at SEQ ID NO: 21, but clarification is required.
The specification teaches increasing GC content and codon optimizing DNA encoding NYESO1 and other antigens on pg 77, lines 6-27.
The specification teaches administering RNA comprising SEQ ID NO: 21 to a wild-type mouse on pg 80, line 5.
However, the specification does not teach the any tumors that express an NYESO1 encoded by a nucleic acid that is at least 75%, 85%, 90%, 100% identical to SEQ ID NO: 21.
The specification does not teach the any RNAs that express an NYESO1 antigen that are 75-99% identical to SEQ ID NO: 21 as encompassed by claim 43.
Most importantly, the specification does teach using a nucleic acid sequence that is 75%, 85%, 90%, 100% identical to SEQ ID NO: 21 to obtain an immune response that is “anti” any tumor that expresses any NYESO1 as broadly encompassed by claims 43, 51, 52.
While an immune response may be obtained against an antigen encoded by SEQ ID NO: 21, if the antigen is not on a tumor, then the immune response is not “anti-tumor” as required in claim 43. The Example on pg 80 does not teach the mouse had a tumor that expressed NYESO1, specifically an NYESO1 encoded by SEQ ID NO: 21, or that the immune response was “anti-tumor” as claimed. The art at the time of filing did not teach an NYESO1 peptide on a tumor that had the sequence above.
Accordingly, the specification lacks written description for any RNA that is 75-99% identical to SEQ ID NO: 21 or obtaining an immune response that is “anti-tumor” against NYESO1 using a sequence that is 75%, 85%, 90%, 100% identical to SEQ ID NO: 21 as broadly encompassed by claims 43, 51, 52.
Response to arguments
Applicants argue the amendment overcomes the rejection. Applicants’ argument is not persuasive because the amendment does not even begin to address the rejection.
C) The specification does not provide written description for using a nucleic acid sequence that is 85%, 90% or 100% identical to SEQ ID NO: 17 to obtain an immune response that is “anti” any tumor as broadly encompassed by claims 55-57.
Gillespie (Cancer Treatment Reviews, 1999, Vol. 25, pg 219-227), Seinel (European J. Cardio-Thoracic Surg., 2004, Vol. 25, No. 1, pg 131-134), and Atanackovic (J. Immunol., March 2004, Vol. 172, No. 5, pg 3289-3296) administered MAGE-A3 to obtain an immune response against various tumors.
The specification says “preferably of the mRNA, encoding “MAGE3A" - if being used in the active (immunostimulatory) composition according to the invention - is shown in Fig. 16 (SEQ ID NO: 16), and — even more preferably — in Fig. 17 (SEQ ID NO: 17)” (pg 11, line 11; pg 12, lines 1-6).
SEQ ID NO: 17 encodes:
MPLEQRSQHCKPEEGLEARGEALGLVGAQAPATEEQEAASSSSTLVEVTLGEVPAAESPDPPQSPQGASSLPTTMNYPLWSQSYEDSSNQEEEGPSTFPDLESEFQAALSRKVAELVHFLLLKYRAREPVTKAEMLGSVVGNWQYFFPVIFSKASSSLQLVFGIELMEVDPIGHLYIFATCLGLSYDGLLGDNQIMPKAGLLIIVLAIIAREGDCAPEEKIWEELSVLEVFEGREDSILGDPKKLLTQHFVQENYLEYRQVPGSDPACYEFLWGPRALVETSYVKVLHHMVKISGGPHISYPPLHEWVLREGEE-
The specification teaches increasing GC content and codon optimizing DNA encoding NYESO1 and other antigens on pg 77, lines 6-27.
The specification teaches administering RNA comprising SEQ ID NO: 17 to a wild-type mouse on pg 80, line 5.
However, the specification does not teach the any tumors that express a MAGE3A encoded by a nucleic acid that is at least 85%, 90%, 100% identical to SEQ ID NO: 17.
The specification does not teach the any RNAs that express a MAGE3A antigen that are 85-99% identical to SEQ ID NO: 17 as encompassed by claim 55-57.
Most importantly, the specification does teach using a nucleic acid sequence that is 85%, 90%, 100% identical to SEQ ID NO: 17 to obtain an immune response that is “anti” any tumor that expresses any MAGE3A as broadly encompassed by claims 55-57.
While an immune response may be obtained against an antigen encoded by SEQ ID NO: 17, if the antigen is not on a tumor, then the immune response is not “anti-tumor” as required in claims 55-57. The Example on pg 80 does not teach the mouse had a tumor that expressed MAGE3A, specifically an MAGE3A encoded by SEQ ID NO: 17, or that the immune response was “anti-tumor” as claimed. The art at the time of filing did not teach an MAGE3A peptide on a tumor that had the sequence above.
Accordingly, the specification lacks written description for RNA encoding a MAGE3A antigen that is 85-99% identical to SEQ ID NO: 17 or obtaining an immune response that is “anti-tumor” against MAGE3A using a sequence that is 85%, 90% or 100% identical to SEQ ID NO: 17 as broadly encompassed by claims 55-57.
Response to arguments
Applicants argue the amendment overcomes the rejection. Applicants’ argument is not persuasive because the amendment does not even begin to address the rejection.
Enablement
Claims 43-62 remain rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for administering RNAs encoding NYESO1 and MAGEA3 to a mammal with a tumor that expresses NYESO1 and MAGE3A such that an anti-tumor immune response occurs, does not reasonably provide enablement for the claims as broadly written. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make/use the invention commensurate in scope with these claims.
A) The specification lacks written description for administering a composition comprising RNAs encoding NYESO1 and MAGEA3 antigens to a mammal that has tumor expressing NYESO1 and MAGE3A without obtaining an antitumor immune response as broadly encompassed by claim 43.
This rejection assumes lung tumors that express NYESO1 and MAGE3A were well-known in the art at the time of filing. If it is found that tumors that express NYESO1 and MAGE3A were unknown and applicants did not teach tumors that express NYESO1 and MAGE3A, then another rejection will be required.
Claim 43 is drawn to “A method of stimulating an anti-tumor immune response in a mammalian subject with a tumor that expresses NYESO1 and MAGE3A, the method comprising administering an effective amount of an immunostimulatory composition ofNY-ESO-1 antigen: and ii) a second isolated RNA encoding MAGE-A3 antigen, wherein the coding region of the first RNA [ ] is at least about 75% identical to the RNA sequence corresponding to SEQ ID NO: 21, wherein each of said first and second isolated RNAs comprise a 5' Cap and Poly-A sequence of 10 to 200 nucleotides and wherein the composition is administered by injection.”
The preamble of claim 43 encompasses treating a mammal that has any tumor that expresses NYESO1 and MAGE3A. Claim 43 requires an active step of administering a first RNA encoding an NY-ESO1 antigen, wherein the first RNA is at least about 75% identical to the nucleic acid sequence of SEQ ID NO: 21 and a second RNA encoding an MAGE-A3 antigen. However, the active step of “administering” in claim 43 does not have any functional language, and the body of the claim does not require tumor size decreases or any therapeutic result occurs. Therefore, the purpose in the preamble is merely an intended use and does not necessarily occur.
Chen (PNAS, 1997, Vol. 94, pg 1914-1918) taught NYESO1 was expressed in human cancers.
Jager (PNAS, 2006, Vol. 103, No. 39, pg 14453-14458) used vectors encoding NYESO1 to induce an immune response in mammals with a tumor.
Davis (PNAS, 2004, Vol. 101, No. 29, pg 10697-10702) administered NYESO1 with ISCOMATRIX to induce an immune response in mammals with a tumor.
Jager (PNAS, 2000, Vol. 97, No. 22, pg 12198-12203) administered NYESO1 to induce an immune response in mammals with a tumor but did not teach the sequence was 85% identical to SEQ ID NO: 21 as required in claims 51, 52.
Odunsi (PNAS, 2007, Vol. 104, No. 31, pg 12837-12842) administered NYESO1 to induce an immune response in mammals with a tumor.
Gillespie (Cancer Treatment Reviews, 1999, Vol. 25, pg 219-227), Seinel (European J. Cardio-Thoracic Surg., 2004, Vol. 25, No. 1, pg 131-134), and Atanackovic (J. Immunol., March 2004, Vol. 172, No. 5, pg 3289-3296) administered MAGE-A3 to obtain an immune response against various tumors in a mammal.
The Examples in the specification are limited to administering RNA to a mammal with a tumor such that an anti-tumor immune response is obtained (pg 77-83).
The specification does not correlate administering RNAs encoding NYESO1 and MAGEA3 antigens to a mammal that has a tumor NYESO1 and MAGEA3 such that an antitumor immune response is obtained to administering the RNAs without obtaining an antitumor immune response as broadly encompassed by claim 43.
Given the lack of guidance in the specification taken with the art at the time of filing, it would have required those of skill undue experimentation to determine how to administer RNAs encoding NYESO1 and MAGEA3 antigens to a mammal that has a tumor NYESO1 and MAGEA3 such that an antitumor immune response is obtained to administering the RNAs without obtaining an antitumor immune response as broadly encompassed by claim 43.
Response to arguments
Applicants argue the amendment overcomes the rejection. Applicants’ argument is not persuasive because the amendment does not even begin to address the rejection.
B) The specification does not enable using a nucleic acid sequence that is 75%, 85%, 90%, 100% identical to SEQ ID NO: 21 to obtain an immune response that is “anti” any tumor that expresses any NYESO1 as broadly encompassed by claims 43, 51, 52.
Chen (PNAS, 1997, Vol. 94, pg 1914-1918) taught NYESO1 was expressed in human cancers but did not teach the sequence was 75%, 85%, 90%, 100% identical to SEQ ID NO: 21 as broadly encompassed by claims 43, 51, 52.
Jager (PNAS, 2006, Vol. 103, No. 39, pg 14453-14458) used vectors encoding NYESO1 to induce an immune response in mammals with a tumor but did not teach the sequence was 75%, 85%, 90%, 100% identical to SEQ ID NO: 21 as broadly encompassed by claims 43, 51, 52.
Davis (PNAS, 2004, Vol. 101, No. 29, pg 10697-10702) administered NYESO1 with ISCOMATRIX to induce an immune response in mammals with a tumor but did not teach the sequence was 75%, 85%, 90%, 100% identical to SEQ ID NO: 21 as broadly encompassed by claims 43, 51, 52.
Jager (PNAS, 2000, Vol. 97, No. 22, pg 12198-12203) administered NYESO1 to induce an immune response in mammals with a tumor but did not teach the sequence was 75%, 85%, 90%, 100% identical to SEQ ID NO: 21 as broadly encompassed by claims 43, 51, 52.
Odunsi (PNAS, 2007, Vol. 104, No. 31, pg 12837-12842) administered NYESO1 to induce an immune response in mammals with a tumor but did not teach the sequence was 75%, 85%, 90%, 100% identical to SEQ ID NO: 21 as broadly encompassed by claims 43, 51, 52.
The specification says “In the context of this invention “NY-ESO-1” is cancer/testis antigen 1B and the preferred sequence of the RNA, preferably of the mRNA, encoding “NY-ESO-1" - if being used in the active (immunostimulatory) composition according to the invention - is shown in Fig. 20 (SEQ ID NO: 20), and — even more preferably — in Fig. 21 (SEQ ID NO: 21)” (pg 15, line 6; pg 16, lines 16-22).
SEQ ID NO: 21 encodes:
MQAEGRGTGGSTGDADGPGGPGIPDGPGGNAGGPGEAGATGGRGPRGAGAARASGPGGGAPRGPHGGAASGLNGCCRCGARGPESRLLEFYLAMPFATPMEAELARRSLAQDAPPLPVPGVLLKEFTVSGNILTIRLTAADHRQLQLSISSCLQQLSLLMWITQCFLPVFLAQPPSGQRR-
PNG
media_image1.png
278
1546
media_image1.png
Greyscale
PNG
media_image2.png
614
1540
media_image2.png
Greyscale
Chen says the sequence reported is in GenBank as U87459.
Human autoimmunogenic cancer/testis antigen NY-ESO-1 mRNA, complete cds
GenBank: U87459.1
FASTA Graphics
Go to:
LOCUS HSU87459 752 bp mRNA linear PRI 22-DEC-1999
DEFINITION Human autoimmunogenic cancer/testis antigen NY-ESO-1 mRNA, complete
cds.
ACCESSION U87459
VERSION U87459.1
KEYWORDS .
SOURCE Homo sapiens (human)
ORGANISM Homo sapiens
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
Catarrhini; Hominidae; Homo.
REFERENCE 1 (bases 1 to 752)
AUTHORS Chen,Y.T., Scanlan,M.J., Sahin,U., Tureci,O., Gure,A.O., Tsang,S.,
Williamson,B., Stockert,E., Pfreundschuh,M. and Old,L.J.
TITLE A testicular antigen aberrantly expressed in human cancers detected
by autologous antibody screening
JOURNAL Proc. Natl. Acad. Sci. U.S.A. 94 (5), 1914-1918 (1997)
PUBMED 9050879
REFERENCE 2 (bases 1 to 752)
AUTHORS Chen,Y.-T.
TITLE Direct Submission
JOURNAL Submitted (28-JAN-1997) Ludwig Institute for Cancer Research, New
York Branch, 1275 York Avenue, New York, NY 10021, USA
FEATURES Location/Qualifiers
source 1..752
/organism="Homo sapiens"
/mol_type="mRNA"
/db_xref="taxon:9606"
/clone_lib="esophageal squamous cell carcinoma expression
cDNA library"
CDS 54..596
/codon_start=1
/product="autoimmunogenic cancer/testis antigen NY-ESO-1"
/protein_id="AAB49693.1"
/translation="MQAEGRGTGGSTGDADGPGGPGIPDGPGGNAGGPGEAGATGGRG
PRGAGAARASGPGGGAPRGPHGGAASGLNGCCRCGARGPESRLLEFYLAMPFATPMEA
ELARRSLAQDAPPLPVPGVLLKEFTVSGNILTIRLTAADHRQLQLSISSCLQQLSLLM
WITQCFLPVFLAQPPSGQRR"
ORIGIN
1 atcctcgtgg gccctgacct tctctctgag agccgggcag aggctccgga gccatgcagg
61 ccgaaggccg gggcacaggg ggttcgacgg gcgatgctga tggcccagga ggccctggca
121 ttcctgatgg cccagggggc aatgctggcg gcccaggaga ggcgggtgcc acgggcggca
181 gaggtccccg gggcgcaggg gcagcaaggg cctcggggcc gggaggaggc gccccgcggg
241 gtccgcatgg cggcgcggct tcagggctga atggatgctg cagatgcggg gccagggggc
301 cggagagccg cctgcttgag ttctacctcg ccatgccttt cgcgacaccc atggaagcag
361 agctggcccg caggagcctg gcccaggatg ccccaccgct tcccgtgcca ggggtgcttc
421 tgaaggagtt cactgtgtcc ggcaacatac tgactatccg actgactgct gcagaccacc
481 gccaactgca gctctccatc agctcctgtc tccagcagct ttccctgttg atgtggatca
541 cgcagtgctt tctgcccgtg tttttggctc agcctccctc agggcagagg cgctaagccc
601 agcctggcgc cccttcctag gtcatgcctc ctcccctagg gaatggtccc agcacgagtg
661 gccagttcat tgtgggggcc tgattgtttg tcgctggagg aggacggctt acatgtttgt
721 ttctgtagaa aataaaactg agctacgaaa aa
Perhaps this is the basis of the coding sequence used by applicants to arrive at SEQ ID NO: 21, but clarification is required.
The specification teaches increasing GC content and codon optimizing DNA encoding NYESO1 and other antigens on pg 77, lines 6-27.
The specification teaches administering RNA comprising SEQ ID NO: 21 to a wild-type mouse on pg 80, line 5.
However, the specification does not teach the any tumors that express an NYESO1 encoded by a nucleic acid that is at least 75%, 85%, 90%, 100% identical to SEQ ID NO: 21.
The specification does not teach the any RNAs that express an NYESO1 antigen that are 75-99% identical to SEQ ID NO: 21 as encompassed by claim 43.
Most importantly, the specification does teach using a nucleic acid sequence that is 75%, 85%, 90%, 100% identical to SEQ ID NO: 21 to obtain an immune response that is “anti” any tumor that expresses any NYESO1 as broadly encompassed by claims 43, 51, 52.
While an immune response may be obtained against an antigen encoded by SEQ ID NO: 21, if the antigen is not on a tumor, then the immune response is not “anti-tumor” as required in claim 43. The Example on pg 80 does not teach the mouse had a tumor that expressed NYESO1, specifically an NYESO1 encoded by SEQ ID NO: 21, or that the immune response was “anti-tumor” as claimed. The art at the time of filing did not teach an NYESO1 peptide on a tumor that had the sequence above.
Given the lack of guidance in the specification taken with the art at the time of filing, it would have required those of skill undue experimentation to determine how to use RNA encoding a NYESO1 antigen that is 85-100% identical to SEQ ID NO: 21 to obtain an immune response that is “anti-tumor” against NYESO1 in a mammal having any tumor expressing any NYESO1 as broadly encompassed by claims 43, 51, 52.
Response to arguments
Applicants argue the amendment overcomes the rejection. Applicants’ argument is not persuasive because the amendment does not even begin to address the rejection.
C) The specification does not enable using a nucleic acid sequence that is 85%, 90% or 100% identical to SEQ ID NO: 17 to obtain an immune response that is “anti” any tumor as broadly encompassed by claims 55-57.
Gillespie (Cancer Treatment Reviews, 1999, Vol. 25, pg 219-227), Seinel (European J. Cardio-Thoracic Surg., 2004, Vol. 25, No. 1, pg 131-134), and Atanackovic (J. Immunol., March 2004, Vol. 172, No. 5, pg 3289-3296) administered MAGE-A3 to obtain an immune response against various tumors.
The specification says “preferably of the mRNA, encoding “MAGE3A" - if being used in the active (immunostimulatory) composition according to the invention - is shown in Fig. 16 (SEQ ID NO: 16), and — even more preferably — in Fig. 17 (SEQ ID NO: 17)” (pg 11, line 11; pg 12, lines 1-6).
SEQ ID NO: 17 encodes:
MPLEQRSQHCKPEEGLEARGEALGLVGAQAPATEEQEAASSSSTLVEVTLGEVPAAESPDPPQSPQGASSLPTTMNYPLWSQSYEDSSNQEEEGPSTFPDLESEFQAALSRKVAELVHFLLLKYRAREPVTKAEMLGSVVGNWQYFFPVIFSKASSSLQLVFGIELMEVDPIGHLYIFATCLGLSYDGLLGDNQIMPKAGLLIIVLAIIAREGDCAPEEKIWEELSVLEVFEGREDSILGDPKKLLTQHFVQENYLEYRQVPGSDPACYEFLWGPRALVETSYVKVLHHMVKISGGPHISYPPLHEWVLREGEE-
The specification teaches increasing GC content and codon optimizing DNA encoding NYESO1 and other antigens on pg 77, lines 6-27.
The specification teaches administering RNA comprising SEQ ID NO: 17 to a wild-type mouse on pg 80, line 5.
However, the specification does not teach the any tumors that express a MAGE3A encoded by a nucleic acid that is at least 85%, 90%, 100% identical to SEQ ID NO: 17.
The specification does not teach the any RNAs that express a MAGE3A antigen that are 85-99% identical to SEQ ID NO: 17 as encompassed by claim 55-57.
Most importantly, the specification does teach using a nucleic acid sequence that is 85%, 90%, 100% identical to SEQ ID NO: 17 to obtain an immune response that is “anti” any tumor that expresses any MAGE3A as broadly encompassed by claims 55-57.
While an immune response may be obtained against an antigen encoded by SEQ ID NO: 17, if the antigen is not on a tumor, then the immune response is not “anti-tumor” as required in claims 55-57. The Example on pg 80 does not teach the mouse had a tumor that expressed MAGE3A, specifically an MAGE3A encoded by SEQ ID NO: 17, or that the immune response was “anti-tumor” as claimed. The art at the time of filing did not teach an MAGE3A peptide on a tumor that had the sequence above.
Given the lack of guidance in the specification taken with the art at the time of filing, it would have required those of skill undue experimentation to determine how to use RNA encoding a MAGE3A antigen that is 85-100% identical to SEQ ID NO: 17 to obtain an immune response that is “anti-tumor” against MAGE3A in a mammal having any tumor expressing any MAGE3A as broadly encompassed by claims 55-57.
Response to arguments
Applicants argue the amendment overcomes the rejection. Applicants’ argument is not persuasive because the amendment does not even begin to address the rejection.
Claim Rejections - 35 USC § 103
The rejection of claims 43-48, 50, 53, 54, 58, 59, 60 under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Von Der Mulbe (20050032730) in view of Gillespie (Cancer Treatment Reviews, 1999, Vol. 25, pg 219-227), Seinel (European J. Cardio-Thoracic Surg., 2004, Vol. 25, No. 1, pg 131-134), and Atanackovic (J. Immunol., March 2004, Vol. 172, No. 5, pg 3289-3296) has been withdrawn. The art at the time of filing did not reasonably teach or suggest administering RNA comprising a nucleic acid sequence that is at least 75% identical to SEQ ID NO: 21 to obtain an immune response that is “anti” any tumor that expresses NYESO1 as required in claim 43.
The rejection of claims 49, 61, 62 under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Von Der Mulbe (20050032730) in view of Gillespie (Cancer Treatment Reviews, 1999, Vol. 25, pg 219-227), Seinel (European J. Cardio-Thoracic Surg., 2004, Vol. 25, No. 1, pg 131-134), and Atanackovic (J. Immunol., March 2004, Vol. 172, No. 5, pg 3289-3296) as applied to claims 43-48, 50, 53, 54, 58, 59, 60 further in view of Saison-Behmoaras, EMBO, 1991, Vol. 10, pg 1111-1118), Kabanov (FEBS Lett, 1990, Vol. 259, No. 2, pg 327-330), Svinarchuk (Biochimie, 1993, Vol. 75, pg 49-54), Shea (Nucleic Acids Res., 1990, Vol. 18, No. 13, pg 3777-3783), Manoharan has been withdrawn. The art at the time of filing did not reasonably teach or suggest administering RNA comprising a nucleic acid sequence that is at least 75% identical to SEQ ID NO: 21 to obtain an immune response that is “anti” any tumor that expresses NYESO1 as required in claim 43.
The art at the time of filing did not reasonably teach or suggest administering RNA comprising a nucleic acid sequence that is at least 75% identical to SEQ ID NO: 21 to obtain an immune response that is “anti” any tumor that expresses NYESO1 as required in claim 43.
Double Patenting
The rejection of claims 43-62 on the ground of nonstatutory double patenting as being unpatentable over claims 12, 13, 33-35, 49-51 of U.S. Patent No. 9352028 (US Application 13750664) has been withdrawn in view of the terminal disclaimer filed 9-10-25.
The rejection of claims 43-62 on the ground of nonstatutory double patenting as being unpatentable over claims 7, 8 of U.S. Patent No. 9572874 (US Application 12994407) has been withdrawn in view of the terminal disclaimer filed 9-10-25.
Conclusion
No claim is 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.
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Michael C. Wilson
/MICHAEL C WILSON/
Primary Examiner, Art Unit 1638