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 .
Priority
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. Acknowledgment is made of applicants' claim for foreign priority to Chinese applications CN 202110099804.1 filed on 01/25/2021. It is noted, however, that applicant has not filed a certified copy of the CN202110099804.1 application as required by 37 CFR 1.55.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 09/30/2024 and 08/01/2023 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
Status of Claims
Claims 1-8 are pending and under exam.
Claim Interpretation
The terms “substantially free of sialylated components” in claim 2 is not given explicit definition in the specification. However [0052] of the specification indicated that “sialylated components of Ustekinumab is between 11.87% and 25.56%, while QX001S expressed by the CHO-S cell line is substantially free of sialylated components.” As such the claim is interpreted to mean that the sialylated components are lower than 11.87%.
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 3-4 and 6 rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as failing to set forth 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.
Claims 3-4 and 6 require a biosimilar drug of Ustekinumab. The term biosimilar is neither expressly defined in the specification, nor does the specification set forth structural, functional or regulatory criteria by which one of ordinary skill in the art could determine whether a given antibody falls within the scope of the claims. As such the metes and bounds of this claim are indefinite.
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.
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
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 1-8 are rejected under 35 U.S.C. 103 as being unpatentable over Pippig et al (WO2018024770A1; Published Feb 8, 2018; hereinafter "Pippig;" See IDS of 08/01/2023), in view of You et al (Appl Microbiol Biotechnol. 2018 Jul; hereinafter "You;" See PTO-892).
Regarding claims 1 and 3-4: Pippig taught a method of producing recombinant Ustekinumab antibody drug product, which is a fully humanized monoclonal antibody against a p40 subunit shared by human IL-12 and human IL-23; a heavy chain amino acid sequence of the fully humanized monoclonal antibody comprising instant SEQ ID NO:1, and a light chain amino acid sequence of the fully humanized monoclonal antibody comprising instant SEQ ID NO:3. (See Pippig claim 4). It is also noted that Pippig disclosed that the drug product has heavy chain sequence according to SEQ ID NO: 1 which is 100% identical to instant SEQ ID NO: 1 (See alignment below). Additionally, Pippig disclosed that the light chain has a sequence according to SEQ ID NO: 2, which is 100% identical to instant SEQ ID NO: 3 (See alignment below).
It is noted that Pippig did not teach “an expression plasmid that expresses the fully humanized monoclonal antibody against the p40 subunit shared by human IL-12 and human IL-23; the expression plasmid comprises a nucleotide sequence encoding the heavy chain amino acid sequence of the fully humanized monoclonal antibody shown as SEQ ID NO:2, and a nucleotide sequence encoding the light chain amino acid sequence of the fully humanized monoclonal antibody shown as SEQ ID NO:4” as required by the claim. However, Pippig taught “culturing Chinese Hamster Ovary (CHO) host cells, genetically modified to express the heavy chain and the light chain of Ustekinumab, in a suitable culture medium under conditions that allow the cells to express the heavy chain and the light chain and to form the recombinant Ustekinumab antibody” (See Pippig Claim 1a). CHO, genetically modified to express the claimed drug product is interpreted to read on expression plasmid that expresses the fully humanized monoclonal antibody against the p40 subunit shared by human IL-12 and human IL-23.
It is noted that the nucleic acid sequence claimed in the instant application: SEQ ID NO: 2 encoding a heavy chain and SEQ ID NO: 4 encoding the light chain was not taught or suggested by Pippig. However, You was directed to producing antibodies with high yield and quality is necessary for clinical applications of antibodies. (See You Abstract). You taught that the yield can be doubled by codon optimization and increased by 50% with the presence of untranslated regions (UTR) specifically for expression in CHO cells. You further taught that the combination of UTR with optimal codon and signal peptide to form an expression vector can result in yield improvement of 150% and correct N-terminal sequences.
As such it was known that codon optimization and nucleotide sequence optimization strategies can improve recombinant antibody expression in CHO cells in view of You. It would have been obvious to a person of ordinary skill in the art to optimize the nucleotide sequences encoding the heavy and light chains of an antibody such as Ustekinumab for enhanced expression in CHO cells by modifying codons or other features with a reasonable expectation of success of improving expression without altering the encoded amino acid sequence. It is also noted that codon optimization represents a finite number of predictable solutions and selection of one optimized nucleotide sequence from among synonymous alternatives would have been routine.
Query 1 EVQLVQSGAEVKKPGESLKISCKGSGYSFTTYWLGWVRQMPGKGLDWIGIMSPVDSDIRY 60
EVQLVQSGAEVKKPGESLKISCKGSGYSFTTYWLGWVRQMPGKGLDWIGIMSPVDSDIRY
Sbjct 1 EVQLVQSGAEVKKPGESLKISCKGSGYSFTTYWLGWVRQMPGKGLDWIGIMSPVDSDIRY 60
Query 61 SPSFQGQVTMSVDKSITTAYLQWNSLKASDTAMYYCARRRPGQGYFDFWGQGTLVTVSSS 120
SPSFQGQVTMSVDKSITTAYLQWNSLKASDTAMYYCARRRPGQGYFDFWGQGTLVTVSSS
Sbjct 61 SPSFQGQVTMSVDKSITTAYLQWNSLKASDTAMYYCARRRPGQGYFDFWGQGTLVTVSSS 120
Query 121 STKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSG 180
STKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSG
Sbjct 121 STKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSG 180
Query 181 LYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGGP 240
LYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGGP
Sbjct 181 LYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGGP 240
Query 241 SVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNS 300
SVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNS
Sbjct 241 SVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNS 300
Query 301 TYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDEL 360
TYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDEL
Sbjct 301 TYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDEL 360
Query 361 TKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQ 420
TKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQ
Sbjct 361 TKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQ 420
Query 421 QGNVFSCSVMHEALHNHYTQKSLSLSPGK 449
QGNVFSCSVMHEALHNHYTQKSLSLSPGK
Sbjct 421 QGNVFSCSVMHEALHNHYTQKSLSLSPGK 449
100% identity between SEQ ID NO: 1 of instant application to SEQ ID NO: 1 of WO2018024770A1
Query 1 DRVTITCRASQGISSWLAWYQQKPEKAPKSLIYAASSLQSGVPSRFSGSGSGTDFTLTIS 60
DRVTITCRASQGISSWLAWYQQKPEKAPKSLIYAASSLQSGVPSRFSGSGSGTDFTLTIS
Sbjct 17 DRVTITCRASQGISSWLAWYQQKPEKAPKSLIYAASSLQSGVPSRFSGSGSGTDFTLTIS 76
Query 61 SLQPEDFATYYCQQYNIYPYTFGQGTKLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLL 120
SLQPEDFATYYCQQYNIYPYTFGQGTKLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLL
Sbjct 77 SLQPEDFATYYCQQYNIYPYTFGQGTKLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLL 136
Query 121 NNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEV 180
NNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEV
Sbjct 137 NNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEV 196
Query 181 THQGLSSPVTKSFNRGEC 198
THQGLSSPVTKSFNRGEC
Sbjct 197 THQGLSSPVTKSFNRGEC 214
100% identity between SEQ ID NO: 3 of instant application to SEQ ID NO: 2 of WO2018024770A1
Regarding claim 2 and 5: Claim 5 of Pippig indicated that the method of production of Ustekinumab has a sialic acid content of <5%; this reads on substantially free of sialylation.
Regarding claims 7-8: The teachings of Pippig in view of You are set forth above. Pippig discloses Ustekinumab or Ustekinumab biosimilar antibodies which bind to p40 subunit of IL-12 and IL-23 using recombinant expression in mammalian cells, including CHO cells. Pippig taught expression constructs comprising nucleotide sequences encoding antibody heavy and light chains, expression vectors containing such sequences and host cells comprising the expression vectors for producing the antibody. While the exact SEQ ID NOs: 2 and 3 are not disclosed in Pippig, You taught that optimization of antibody sequences for CHO cell expression increases antibody expression. You used expression vectors for expressing antibody heavy and light chains. As such the teachings of Pippig in view of You taught that optimized nucleotide sequences encoding a given antibody amino acid sequence can be routinely incorporated into host cells to achieve improved expression with predictable results.
Conclusion
No claim is allowed.
No claim is free art.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JAGAMYA VIJAYARAGHAVAN whose telephone number is (703)756-5934. The examiner can normally be reached 9:00a-5:00p.
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/JAGAMYA NMN VIJAYARAGHAVAN/ Examiner, Art Unit 1633
/EVELYN Y PYLA/Primary Examiner, Art Unit 1633