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 .
Amendments
In the reply filed 11/10/2025, Applicant has amended Claims 1-3 and 11.
Claims 4-5, 9, 12, 17-26 are pending but withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a non-elected invention, there being no allowable generic or linking claim.
Claims 1-3, 6-8, 10-11, and 13-16 are under consideration.
Withdrawn 35 USC § 112
The prior rejection of Claim 11 under 35 U.S.C. § 112(b) pre-AIA 2nd paragraph as being indefinite is withdrawn in light of Applicant’s amendments of Claim 11 to describe the IgG constant heavy chain region.
Withdrawn 35 USC § 102
The prior rejection of Claims 1-3, 7, 8, 10, 13-16 under 35 U.S.C. 102(a)(1) as being anticipated by Gelinas et al., (US2007/0154481, filed 12/08/2006) is withdrawn in light of Applicant’s amendment of Claim 1 to limit the anti-IL-6 antibody to comprising the nucleic acid sequence of SEQ ID NO:1, which is a limitation Gelinas does not anticipate. Specifically, Gelinas only teaches fragments of SEQ ID NO:1 and 2.
Withdrawn 35 USC § 103
The prior rejection of Claims 1-3, 7-8, 10-11, and 13-16 under 35 U.S.C. 103 as being unpatentable over Bolen et al. (WO2015/105926, filed 1/08/2015, published 7/16/2015, prior art of record), in view of Chen et al. (US 7,833,755, filed 5/22/2009, patented 11/16/2010, prior art of record) is withdrawn in light of Applicant’s amendment of Claim 1 to limit the anti-IL-6 antibody to comprising the nucleic acid sequence of SEQ ID NO:1, which is a limitation neither Bolen nor Chen make obvious. Specifically, Bolen and Chen only teach fragments of SEQ ID NO:1 and 2.
The prior rejection of Claim 6 under 35 U.S.C. 103 as being unpatentable over Bolen et al. (WO2015/105926, filed 1/08/2015, published 7/16/2015, prior art of record), in view of Chen et al. (US 7,833,755, filed 5/22/2009, patented 11/16/2010) is withdrawn in light of Applicant’s amendment of Claim 1 to limit the anti-IL-6 antibody to comprising the nucleic acid sequence of SEQ ID NO:1
The prior rejection of Claim 6 under 35 U.S.C. 103 as being unpatentable over Bolen et al. (WO2015/105926, filed 1/08/2015, published 7/16/2015, prior art of record), in view of Chen et al. (US 7,833,755, filed 5/22/2009, patented 11/16/2010), as applied to claim 1, in further view of Elliot et al. (Cancer Immunotherapy, Cancer Vaccine III, 24:225, May, 01, 2016, see IDS filed 6/17/2024) is withdrawn in light of Applicant’s amendment of Claim 1 to limit the anti-IL-6 antibody to comprising the nucleic acid sequence of SEQ ID NO:1
New Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1-3, 7-8, 10, 13-16 are rejected under 35 U.S.C. 102(a)(1)/(a)(2) as being anticipated by Smith et al., (WO2015/054293, filed 10/07/2014, published 4/16/2015)
With respect to claim 1, Smith teaches a composition comprising one or more nucleic acid molecules encoding the synthetic (i.e., recombinant) anti-IL-6 antibody ([054, 0166-0169, 0216-0255, 0355-0358], see Table 1).
Specifically, Smith teaches the anti-IL-6 antibody of clazakizumab, which comprises the heavy chain variable domain encoded by the polynucleotide of SEQ ID NO:700 and encodes the amino acid sequence of SEQ ID NO:19 (see translation of SEQ ID NO:700 above SEQ ID NO:19 below):
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Importantly, the amino acid sequence of SEQ ID NO:19 of Smith is a 100% match to the heavy chain variable fragment of instant SEQ ID NO:8.
Furthermore, Smith teaches the anti-IL-6 antibody of clazakizumab, comprises the light chain variable domain and human IgG1 kappa constant region (highlighted) encoded by the polynucleotide of SEQ ID NO:701 and encodes the amino acid sequence of SEQ ID NO:20 (see translation of SEQ ID NO:701 above SEQ ID NO:20 below):
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Importantly, the amino acid sequence of SEQ ID NO:20 of Smith is a 100% match to the light chain variable fragment of instant SEQ ID NO:8.
Thus, Smith teaches a composition comprising one or more nucleic acids encoding a synthetic IL-6 antibody, wherein the IL-6 synthetic antibody comprises an amino acid sequence of a fragment of SEQ ID NO:8.
Finally, in regard to the nucleic acids of Smith comprising a nucleotide sequence of a fragment of nucleic acid sequence of SEQ ID NO:7 (which encodes the amino acid sequence of SEQ ID NO:8), as stated supra, the term “fragment” of the polynucleotide of SEQ ID NO:7 is broadly defined by Applicant’s specification with no explicit length or functional requirements and reasonably encompasses nucleic acid sequences as short as two (2) nucleotides in the variable region. Thus, the nucleic acids of Smith (e.g., SEQ ID NO:700 and 701) anticipate a fragment of SEQ ID NO:7.
In regard to claim 2, as stated supra, Smith anticipates a fragment of the amino acid sequence of SEQ ID NO:8.
In regard to claim 3, as stated supra, Smith anticipates a fragment of the nucleic acid sequence of SEQ ID NO:7.
In regard to claim 7, Smith teaches the polynucleotide encoding the antibody further comprises a nucleotide sequence encoding a cleavage domain after the leader peptide [0174, 0214, 0246].
In regard to claim 8, Smith teaches a vector comprising a nucleotide sequence encoding a variable heavy chain and a variable light chain region of an anti-IL-6 antibody comprising a fragment of SEQ ID NO:2 ([0238, 0248]).
In regard to claim 10, as stated supra, Smith teaches the human IgG1 kappa constant light chain region, as well as a constant heavy chain region [0054, 0064-0065, 0175, 0213]
In regard to claim 13, Smith teaches the nucleic acid molecule encodes leader (alias secretion signal peptide) sequence [0174, 0214, 0246].
In regard to claim 14, Smith teaches the nucleic acid molecule comprises an expression vector (0238, 0248)
In regard to claims 15 and 16, Smith teaches the nucleic acid molecule composition is transfected into cells ([0355-0358]), which requires a sterile solution and some sort of transfection facilitating agent, and therefore anticipates the generic pharmaceutical composition as claimed. In regard to the “excipient” of claim 16, Applicant’s specification indicates a pharmaceutically acceptable excipient can be a transfection facilitating agent [00180].
Accordingly, Smith anticipates instant claims.
RESPONSE TO ARGUMENTS
Applicant's arguments filed on 11/10/2025 are acknowledged.
Applicant argues that the full length SEQ ID NO:1 is not anticipated by the cited prior art.
Applicant's arguments have been fully considered and they are found persuasive.
However, as necessitated by Applicant’s amendments, the Examiner has put forth a new anticipation rejection of instant claims based on a fragment of the amino acid sequence of SEQ ID NO:8, and a fragment of the nucleic acid sequence of SEQ ID NO:7.
New 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 of this title, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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 6 and 11 are rejected under 35 U.S.C. 103 as being unpatentable over Smith et al., (WO2015/054293, filed 10/07/2014, published 4/16/2015) in view of Bolen et al. (WO2015/105926, filed 1/08/2015, published 7/16/2015, prior art of record)
As discussed previously, Smith teaches a composition comprising one or more nucleic acid molecules encoding one or more synthetic anti-IL-6 antibodies, wherein the one or more nucleic acids comprise a nucleic acid fragment of SEQ ID NO:7, and the one or more synthetic anti-IL-6 antibodies comprises an amino acid sequence fragment of SEQ ID NO:8.
In regard to claim 6, although Smith teaches including an IL-6 receptor (i.e., CD126) antibody such as tocilizumab [0071, 0200], they are silent to the composition further comprising a nucleic acid that encodes an anti-CD126 antibody.
In regard to claim 6, Bolen also teaches a nucleic acid that encodes a synthetic IL-6 receptor (i.e., CD126) antibody such as tocilizumab [00553-00572].
Furthermore, in regard to claim 6, Bolen teaches that both the anti-IL-6 antibody and the anti-IL-6 receptor antibody are used for treating autoimmune diseases [00554, 00559, 00875-00877].
Accordingly, it would have been prima facie obvious to one of ordinary skill in the art at the time of filing to prepare a composition comprising one or more polynucleotides encoding the anti-IL-6 antibody as taught by Smith, and combine and a polynucleotide encoding the anti-IL-6 receptor antibody as taught by Bolen with a reasonable expectation of success. The ordinary skilled artisan would have been motivated to do because the combination for producing the two types of antibodies is suggested by Smith and Bolen for treating autoimmune diseases. Furthermore, although Smith teaches in vivo expression [0197], Bolen teaches using a nucleic acid composition of the antibodies in vivo via direct translation overcomes many of the problems associated with traditional antibody therapy [009-0010]. Furthermore, MPEP 2144.06 indicates that “It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art.” In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980).
In regard to claim 11, as stated supra, although Smith teaches one or more nucleic acids encoding the variable heavy chain region of an anti-IL-6 antibody, a constant heavy chain region of human IgG1, a variable light chain region of the anti-IL-6 antibody, and a constant light chain region of IgG1 kappa, they are silent to a single nucleic acid encoding these elements separated by a cleavable linker domain
In regard to claim 11, Bolen teaches a polynucleotide encoding a
two-protein chain antibody on a single polynucleotide strand, wherein the antibody
comprise a variable heavy chain region, a constant heavy chain region of human lgG1
(alias IGHG1), a cleavable linker domain, a variable light chain region, and constant light chain region of human lgG1 kappa ([0042, 00872, 01164, 01292-01295, 01813], see Fig. 5A).
Accordingly, it would have been prima facie obvious to one of ordinary skill in the art at the time of filing to prepare a composition comprising one or more polynucleotides encoding the variable heavy chain region of an anti-IL-6 antibody, a constant heavy chain region of human IgG1, a variable light chain region of the anti-IL-6 antibody, and a constant light chain region of IgG1 kappa as taught by Smith, and combine the one or more polynucleotides into a single polynucleotide encoding the anti-IL-6 antibody heavy and light chains with a linking cleavage domain as taught by Bolen with a reasonable expectation of success. The ordinary skilled artisan would have been motivated to do because although Smith teaches the polynucleotides are in in expression vectors for transfection of cells [0238, 0248, 0355-0358], a single polynucleotide would ensure that cells would have both chains of the antibody at the correct stoichiometry.
Hence, the claimed invention as a whole was prima facie obvious in the absence of evidence to the contrary.
RESPONSE TO ARGUMENTS
Applicant's arguments filed on 11/10/2025 are acknowledged and have been addressed supra.
Claim 6 is rejected under 35 U.S.C. 103 as being unpatentable over Smith et al., (WO2015/054293, filed 10/07/2014, published 4/16/2015) in view of Elliot et al. (Cancer Immunotherapy, Cancer Vaccine III, 24:225, May, 01, 2016, see IDS filed 6/17/2024)
Overcoming Rejection by Declaration under 37 CFR 1.130
Elliot et al. (Cancer Immunotherapy, Cancer Vaccine III, 24:225, May, 01, 2016, see IDS filed 6/17/2024) appears to be Applicant’s own work. Applicant may rely on the exception under 35 U.S.C. 102(b)(1)(A) to overcome this rejection under 35 U.S.C. 102(a)(1) by a showing under 37 CFR 1.130(a) that the subject matter disclosed in the reference was obtained directly or indirectly from the inventor or a joint inventor of this application, and is therefore not prior art under 35 U.S.C. 102(a)(1) . Alternatively, applicant may rely on the exception under 35 U.S.C. 102(b)(1)(B) by providing evidence of a prior public disclosure via an affidavit or declaration under 37 CFR 1.130(b).
As discussed previously, Smith teaches a composition comprising one or more nucleic acid molecules encoding one or more synthetic anti-IL-6 antibodies, wherein the one or more nucleic acids comprise a nucleic acid fragment of SEQ ID NO:7, and the one or more synthetic anti-IL-6 antibodies comprises an amino acid sequence fragment of SEQ ID NO:8.
In regard to claim 6, although Smith teaches including an IL-6 receptor (i.e., CD126) antibody such as tocilizumab [0071, 0200], they are silent to the composition further comprising a nucleic acid that encodes an anti-CD126 antibody.
In regard to claim 6, Elliott teaches that a polynucleotide encoding the anti-IL-6 antibody can be used in combination with a polynucleotide encoding anti-IL-6 receptor to treat autoimmune diseases.
Accordingly, it would have been prima facie obvious to one of ordinary skill in the art at the time of filing to prepare a composition comprising a polynucleotide encoding the anti-IL-6 antibody as Smith, and combine and a second polynucleotide encoding the anti-IL-6 receptor antibody as taught by Elliot with a reasonable expectation of success. The ordinary skilled artisan would have been motivated to do because the combination is suggested by Elliott as an alternative to protein antibody therapies for treating autoimmune diseases. Furthermore, MPEP 2144.06 indicates that “It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art.” In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980).
Hence, the claimed invention as a whole was prima facie obvious in the absence of evidence to the contrary.
RESPONSE TO ARGUMENTS
Applicant's arguments filed on 11/10/2025 are acknowledged and have been addressed supra.
Allowable subject matter
The prior art does not teach nor reasonably suggest the codon optimized nucleic acid sequences of SEQ ID NOs: 1, 3, 5, and 7, which encode the heavy chain and light chain variable regions of anti-IL-6 antibodies.
Conclusion
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 extension fee 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 date of this final action.
No claims are allowed.
Examiner Contact Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ARTHUR S LEONARD whose telephone number is (571)270-3073. The examiner can normally be reached on Mon-Fri 9am-5pm.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, James Doug Schultz can be reached on 571-272-0763. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/ARTHUR S LEONARD/Examiner, Art Unit 1631