DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
This Office action is in response to the communication filed 6-22-26.
Claims 1-9, 14-16 are pending in the instant application.
Election/Restrictions
Claims 10-13 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention and have been canceled, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 6-22-26.
Applicant’s election without traverse of Group I, claims 1-9, 14-16, in the reply filed on 6-22-26 is acknowledged.
Claim Objections
Claim 2 is objected to because of the following informalities: In line 2 of claim 2, “disorders comprise” appears to be grammatically inconsistent (e.g. perhaps replacing “disorders comprise” with – disorder comprises – would be remedial). Appropriate correction is required.
Claim Rejections - 35 USC § 103
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.
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.
Claim(s) 1-9, 14-16 is/are rejected under 35 U.S.C. 103 as being unpatentable over Erbe et al (US 2020/0113927), Querbes et al (WO 2016/057893), Erbe et al (WO 2019/014530),and Liu et al (Clinical Biochemistry Vol. 49, pages 1133-1139 (2016)), the combination in view of FDA Report on Lumasiran (a.k.a. Oxlumo (approved 2020), and ClinicalTrials.gov (A Study to Evaluate DCR-PHXC in Children and Adults With Primary Hyperoxaluria Type 1 and Primary Hyperoxaluria Type 2 (Study Started 10-28-2019)).
The claims are drawn to methods of treating an oxalate-related disorder in a patient receiving dialysis treatment who does not suffer from Primary Hyperoxaluria 1-3 (PH) comprising the administration of Lumasiran and/or Nedosiran, which oxalate-related disorders comprise cardiovascular disease associated with calcium oxalate deposition in the organs of a non-PH patient, which disease is associated with plasma or serum oxalate concentration >20uM or 30uM, wherein the dosage of administration achieves a plasma or serum oxalate concentration of <30uM, which cardiovascular events are associated with sudden cardiac death or congestive heart failure.
Erbe et al (US 2020/0113927) teach the role of lactate dehydrogenase (LDH) and hydroxyacid oxidase (HAO1) in oxalate pathway associated diseases, disorders and conditions, and the design and optimization of inhibitory oligonucleotides targeting LDH and HAO1 for treating oxalate pathway associated diseases. (Abstract, Figure 1A, text on page 1, para 0063-0084). Erbe teaches that calcium oxalate deposits occur in various organs, including the thyroid, breasts, kidneys, bones, bone marrow, myocardium and the cardiac conduction system, leading to cardiomyopathy, heart block and other cardiac conduction defects, and vascular disease (paragraphs 0831, 0836, claims 1-30).
Querbes et al (WO 2016/057893) teach the optimization and testing of siRNA molecules targeting Hydroxyacid Oxidase (HAO1) for treating HAO1 related conditions and diseases (claims 1-65, 74-90).
Erbe et al (WO 2019/014530) teach the design, testing and optimization of dsRNA compositions targeting lactate dehydrogenase (LDH) and Hydroxyacid Oxidase (HAO1) for treating patients having oxalate pathway associated diseases, disorders or conditions (Abstract, claims 1-66, 80-94, 104-108).
Liu et al (Clinical Biochemistry Vol. 49, pages 1133-1139 (2016)) (See IDS filed 9-1-2023) address concerns for plasma oxalate levels in prevalent dialysis patients when plasma oxalate concentrations reach greater than 30uM. Exceeding this concentration threshold, oxalate has the potential to precipitate with calcium that can deposit pathologically in organs, leading to secondary oxalosis (see esp. Introduction, pages 1133-1134). Liu teaches the clinical history of their study population to have coronary artery disease, peripheral vascular disease and hyperlipidemia (See Table 1 on page 1135).
The primary references do not teach Lumasiran or Nedosiran.
FDA Report on Lumasiran (a.k.a. Oxlumo (approved 2020) reports clinical trials with Lumasiran, which is a dsRNA molecule targeting lactate dehydrogenase.
ClinicalTrials.gov (A Study to Evaluate DCR-PHXC in Children and Adults With Primary Hyperoxaluria Type 1 and Primary Hyperoxaluria Type 2 (Study Started 10-28-2019) report clinical trials with Nedosiran, which is a dsRNA molecule targeting Hydroxyacid Oxidase (HAO1).
It would have been obvious to target lactate dehydrogenase (LDH) and/or Hydroxyacid Oxidase (HAO1) for treating patients on dialysis and suffering from non Primary Hyperoxaluria 1-3 (PH) because Erbe, Erbe and Querbes taught the inhibition of these target genes using inhibitory oligonucleotides for treating other conditions besides PH 1-3, including cardiac conditions. One would have been motivated to utilize Lumasiran and/or Nedosiran for treating non PH 1-3 oxalate related disorders because these drugs were well known in the art to effectively target and inhibit the expression of LDH and HOA1 respectively, as revealed in the FDA Report and the Study to Evaluate DCR-PHXC. For these and the aforementioned reasons, the instant invention would have been obvious to one of ordinary skill in the art prior to the effective filing date of the instant invention.
Conclusion
Certain papers related to this application may be submitted to Art Unit 1637 by facsimile transmission. The faxing of such papers must conform with the notices published in the Official Gazette, 1156 OG 61 (November 16, 1993) and 1157 OG 94 (December 28, 1993) (see 37 C.F.R. ' 1.6(d)). The official fax telephone number for the Group is 571-273-8300. NOTE: If Applicant does submit a paper by fax, the original signed copy should be retained by applicant or applicant's representative. NO DUPLICATE COPIES SHOULD BE SUBMITTED so as to avoid the processing of duplicate papers in the Office.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Jane Zara whose telephone number is (571) 272-0765. The examiner’s office hours are generally Monday-Friday, 10:30am - 7pm. If attempts to reach the examiner by telephone are unsuccessful, the examiner's supervisor, Jennifer Dunston, can be reached on (571)-272-2916. Any inquiry of a general nature or relating to the status of this application should be directed to the Group receptionist whose telephone number is (703) 308-0196.
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Jane Zara
8-14-26
/JANE J ZARA/Primary Examiner, Art Unit 1637
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