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 .
Election/Restrictions
Applicant’s election of Group I, Species A, Item I, drawn to a method for reducing ECM protein expression and/or secretion by inhibiting or reducing NKD2 gene expression in a cell, in the reply filed on 02/03/2026 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Claims 3 and 5-29 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention or species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 02/03/2026.
Claims 1, 2, and 4 are examined on the merits in the present Office Action.
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.
Claim 4 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim 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.
Regarding claim 4, the phrase "preferably" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
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, 2 and 4 are rejected under 35 U.S.C. 103 as being unpatentable over Zhao et al (Zhao, S et al. “NKD2, a negative regulator of Wnt signaling, suppresses tumor growth and metastasis in osteosarcoma.” Oncogene vol. 34,39 (2015): 5069-79. doi:10.1038/onc.2014.429), hereinafter Zhao, in view of Federico et al (Federico, Giuseppina, et al. "Tubular Dickkopf-3 promotes the development of renal atrophy and fibrosis." JCI insight 1.1 (2016): e84916), hereinafter Federico, and McSwigen (US20130012567A1), hereinafter McSwigen.
Zhao teaches that naked cuticle homolog 2 (NKD2) upregulates expression of Dickkopf-related protein 3 (DKK3), a secreted signaling protein, by approximately 14-fold (Page 6), indicating that NKD2 is a strong upstream regulator of DKK3 expression. In addition, NKD2 increased the expression of extracellular matrix (ECM) proteins (Page 6).
Zhao does not teach a method for reducing ECM protein expression and/or secretion by a cell comprising inhibiting or reducing NKD2 gene expression in the cell, wherein the cell is a kidney cell and inhibition or reduction of NKD2 gene expression is achieved by NKD2 gene knockdown, knockout, conditional gene knockout, gene alteration, RNAi, siRNA, and/or antisense RNA.
However, Federico teaches that DKK3 is a stress-induced secreted glycoprotein produced by renal tubular epithelial cells that functions as a profibrotic signaling molecule. It was demonstrated that reduction or abrogation of DKK3 results in decreased tubular atrophy and reduced interstitial extracellular matrix (ECM) accumulation in models of renal fibrosis (Abstract). In addition, there was diminished accumulation of alpha smooth muscle actin positive myofibroblasts in the DKK3 deficient mice (first paragraph under results on Page 2). Thus, Federico establishes that DKK3 promotes kidney fibrosis and that decreasing DKK3 reduces ECM deposition and fibrotic progression.
McSwigen teaches methods and reagents useful in modulating gene expression in a variety of applications, including therapeutic applications. Specifically, disclosed are synthetic chemically modified small nucleic acid molecules, such as short interfering nucleic acid (siNA), short interfering RNA (siRNA), double-stranded RNA (dsRNA), micro-RNA (miRNA), and short hairpin RNA (shRNA) molecules capable of mediating RNA interference (RNAi) against target nucleic acid sequences. The small nucleic acid molecules are useful in the treatment of any disease or condition that responds to modulation of gene expression or activity in a cell, tissue, or organism (Abstract).
It would have been obvious to one of ordinary skill in the art to apply the gene knockdown methods of McSwigen to reduce NKD2 gene expression, particularly in kidney cells such as myofibroblasts. One of ordinary skill in the art would have been motivated to do so since NKD2 upregulates DKK3 expression as taught by Zhao; and DKK3 promotes kidney fibrosis and ECM accumulation as taught by Federico. Further, the small nucleic acid molecules taught by McSwigen are useful in the treatment of any disease or condition that response to modulation of gene expression or activity in a cell. Therefore, one of ordinary skill in the art would reasonably expect that reducing NKD2 gene expression in a kidney cell by gene silencing techniques (e.g. siRNA or RNAi) will decrease DKK3 levels and, in turn, downstream ECM protein accumulation and renal fibrosis.
Conclusion
No claims are allowable.
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/LIA E TAYLOR/Examiner, Art Unit 1641
/MISOOK YU/Supervisory Patent Examiner, Art Unit 1641
