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 .
DETAILED ACTION
Election/Restrictions
Applicant’s election without traverse of species: diabetic kidney disease and abnormal epithelium physiology in the reply filed 06/02/2025 is acknowledged.
Applicant's election with traverse of group C, a form of IL-33, in the reply filed on 06/02/2025 is acknowledged. The traversal is on the ground(s) that “the present invention relates to the use of an anti-IL- 33 therapeutic agent that both (i) attenuates or inhibits activity of reduced IL-33 protein (red IL- 33) and thereby inhibits ST2 signaling, and (ii) attenuates or inhibits activity of oxidized IL-33 protein (oxIL-33) and thereby inhibits RAGE signaling. Thus, reduced IL-33 protein and oxidized IL-33 protein are not directed to independent or distinct inventions”. This is found persuasive because the prior art indicates that reduce and oxidized forms of IL-33 are not distinct and thereby should not be split in a species election. As such, the species election requirement for group C is withdrawn and both the oxidized and reduced forms of IL-33 will be examined.
Claims 37-40, 44, 46, 56-57, 60-62, and 65-67 are now under consideration in the instant Office Action.
Withdrawn Rejections
Rejections of claims 37-44, 46, 48, 56-57, 60-62, 65-67 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or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement are hereby withdrawn in view of amendments to the claims to include sufficient structural detail for the antibody.
Rejections of claims 37-44, 46, 48, 56, 60-62, 65-67 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for an antibody with the disclosed sequences being used in a method to treat kidney injury, does not reasonably provide enablement for any anti-IL-33 therapeutic agent to be used in a method to treat kidney injury by attenuating or inhibiting IL-33-mediated ST2 signaling and IL-33-mediated RAGE signaling are hereby withdrawn in view of amendments to the claims.
Rejections of claims 37-42, 61-62, and 65-67 under 35 U.S.C. 102(a)(1) as being anticipated by Ackay et al. (in IDS filed 10/06/2022) are hereby withdrawn in view of amendments to the claims.
Rejections of claims 37-41, 60-61, and 65 on the ground of nonstatutory double patenting as being unpatentable over claims 4 and 10 of U.S. Patent No. US 10,668,150 B2, hereinafter ‘150, in view of Ackay (in IDS filed 10/06/2022) and Cohen et al. (in IDS filed 10/06/2022) are hereby withdrawn in view of amendments to the claims.
Rejections of claims 37-41, 60-61, and 65 on the ground of nonstatutory double patenting as being unpatentable over claims 1-3 and 8 of U.S. Patent No. US 11,738,081 B2, hereinafter ‘081, in view of Ackay (in IDS filed 10/06/2022) and Cohen et al. (in IDS filed 10/06/2022) are hereby withdrawn in view of amendments to the claims.
Modified Rejections Necessitated by Amendment
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 37-40, 44, 46, 56-57, 60-62, and 65-67 are rejected under 35 U.S.C. 103 as being unpatentable over Cohen et al. (WO 2016/156440 A1, in IDS filed 10/06/2022), in view of Ackay et al. (in IDS filed 10/06/2022), and Tonacci et al. 2019 (in instant PTO-892).
Cohen et al. teach isolated IL-33 proteins, active fragments thereof and antibodies, antigen binding fragments thereof, against IL-33 proteins and methods of modulating cytokine activity, e.g., for the purpose of treating immune and inflammatory disorders, see Abstract. Cohen et al. also teach that the biding molecule, which can be a monoclonal antibody, attenuates or inhibits activity of reduced IL-33 protein, which in turn catalyzes the oxidation of reduced IL-33 to IL-33 DSB, see claims 32 and 5-6 respectively.
Cohen et al. also teach a method for treating a subject with inflammation, wherein the binding molecule or antigen-binding fragment thereof inhibits RAGE mediated effects (claim 48) and a method for preventing an inflammatory response in a subject with inflammation, wherein the binding molecule or antigen-binding fragment thereof inhibits IL-33 driven cytokine production and/or RAGE mediated effects (claim 49). Cohen et al. teaches the following sequences for the anti-IL-33 binding antibody:
SEQ ID NO: 522, which is a 100% match to instant SEQ ID NO: 1.
SEQ ID NO: 3, which is a 100% match to instant SEQ ID NO: 37.
SEQ ID NO: 344, which is a 100% match to instant SEQ ID NO: 38.
SEQ ID NO: 395, which is a 100% match to instant SEQ ID NO: 39.
SEQ ID NO: 618, which is a 100% match to instant SEQ ID NO: 19.
SEQ ID NO: 428, which is a 100% match to instant SEQ ID NO: 40.
SEQ ID NO: 589, which is a 100% match to instant SEQ ID NO: 41.
SEQ ID NO: 430, which is a 100% match to instant SEQ ID NO: 42.
Cohen et al. describes how in “one embodiment, the present inventors have identified an antibody that preferentially binds the oxidized form but surprisingly attenuates the activity of the reduced form by essentially catalyzing the conversion of the reduced form to the oxidized form. Advantageously this mechanism simply augments the in vivo mechanism for terminating the signaling through ST2”, see paragraph 11. Cohen et al. also describe that “the reduced form appears to be the active form of the protein which generates the signal cascade and in fact in vivo it appears that the reduced form is converted into the oxidized form as a mechanism for terminating the signaling through ST2”, see paragraph 10.
However, Cohen et al. does not teach the connection between IL-33, inflammation, and the ST2 signaling pathway in kidney disease states. Ackay et al. remedies this deficiency.
Ackay et al. teaches that “inflammation contributes to the pathogenesis of acute kidney injury (AKI). IL-33 is a proinflammatory cytokine... To determine whether IL-33 promotes injury, we administered soluble ST2 (sST2), a fusion protein that neutralizes IL-33 activity by acting as a decoy receptor. Compared with cisplatin-induced AKI in untreated mice, mice treated with sST2 had fewer CD4 T cells infiltrate the kidney, lower serum creatinine, and reduced acute tubular necrosis (ATN) and apoptosis. In contrast, administration of recombinant IL-33 (rIL-33) exacerbated cisplatin-induced AKI, measured by an increase in CD4 T cell infiltration, serum creatinine, ATN, and apoptosis; this did not occur in CD4-deficient mice, suggesting that CD4 T cells mediate the injurious effect of IL-33... These data suggest that inhibiting IL-33 or CXCL1 may have therapeutic potential in AKI”, see Abstract. The effect is that IL33 is blocked, so at least those kidney diseases that are caused or aggravated by IL33 are relieved. Ackay teaches that “IL-33 was predominantly expressed in glomeruli, blood vessels, and peritubular capillaries in the kidney. Next, we determined the intracellular localization of IL-33 in the kidney. IL-33 is identical to nuclear factor expressed in high endothelial venules (NF-HEV)”, see Discussion.
However, Cohen et al. and Ackay et al. do not teach chronic kidney diseases as a result of diabetes. Tonacci et al. remedies this deficiency.
Tonacci et al. teaches how “different disorders are related to the activity of IL-33, ST2 or their axis, including cardiovascular diseases, or renal disturbances, like chronic kidney disease (CKD), an immune inflammatory disease whose function is related to the presence of inflammatory biomarkers as much as the kidney function decline”, see page 2. Tonacci et al. perform a literature review regarding the IL-33/ST2 axis involvement in diabetic kidney disease and related neuropathies. The review included studies which investigated whether IL-33 can be used to show the early stage of kidney injury in diabetic patients, see page 4. Tonacci et al. found that “according to the literature, sST2 serum levels were higher in CKD and associated with the severity of the disease, possibly having a role in the development of CKD or as a marker of disease severity. The role for sST2 appears to be stronger than the role of IL-33, as demonstrated by the lack of association between the increased IL-33 levels and kidney injury in diabetic nephropathy, with such increase possibly associated with diabetic disease. Taken together with the evidences of other studies, … , such retrievals suggest that the serum levels of sST2 are more relevant in investigating the deterioration of kidney function with respect to the serum levels of IL-33” and “the involvement of the ST2 expression was clear in all studies published to date, making it a reliable factor alone, or taken together, with IL-33, for the involvement in diabetic complications”, see page 5.
This meets the limitations of instant claims 37 and 44 wherein an anti-IL-33 antibody with the same sequences is used in a method of treating chronic kidney disease by attenuating or inhibiting IL-33-mediated ST2 signaling and IL-33-mediated RAGE signaling, instant claim 38 where the RAGE signaling is IL-33 mediated RAGE-EGFR signaling, instant claims 39 and 40 wherein the anti-IL-33 antibody attenuates or inhibits the activity of reduced IL-33 and oxidized IL-33 protein, instant claims 46 and 60 wherein the therapeutic agent is a monoclonal antibody, instant claims 56-57 wherein the sequences are taught above, instant claim 61 wherein the inhibition or attenuation of RAGE-EGFR signaling down-regulates or inhibits RAGE-EGFR mediated effects, instant claim 65 wherein the inhibition or attenuation of ST2 signaling down-regulates or inhibits RAGE-EGFR mediated effects, and instant claims 62 and 66 wherein the kidney injury comprises inflammation or an inflammatory kidney injury, and instant claim 67 wherein the abnormal inflammation is in the glomeruli.
It would be obvious at the time of the instant invention to use the anti-IL-33 antibody taught by Cohen et al., which is an inhibitor that results in attenuating or inhibit IL-33 mediated ST2 signaling and IL-33 mediated RAGE signaling, with the teachings of Ackay et al. and Tonacci et al. which state that the IL-33/ST2 pathway is implicated across a broad genus of kidney diseases as a contributor to the pathogenesis of kidney injuries and that inhibiting this pathway is a viable options for therapeutics. One would be motivated to combine the teachings with the expectation of using the anti-IL-33 antibodies to treat chronic kidney disease by attenuating or inhibit IL-33 mediated ST2 signaling and IL-33 mediated RAGE signaling in the affected areas due to the teaching of Tonacci et al., which disclose that IL-33 inhibition and the IL-33/ST2 axis plays an important role in kidney disease pathogenesis by worsening chronic inflammatory diseases, see Abstract. As such, the antibody sequences are the same between the prior art and the instant claims. Given that structure confers function, the same pathways involved in a method of treating using the same antibody would be implicated and thus read on the instantly claimed subject matter.
Therefore, claims 37-40, 44, 46, 56-57, 60-62, and 65-67 are rejected as obvious over Cohen et al., Ackay et al., and Tonacci et al.
Response to Arguments
Applicant's arguments filed 09/30/2025 have been fully considered but they are not persuasive.
Applicant argues that the claim amendments to recite “chronic kidney disease” from “acute kidney injury” obviate the rejection and that “the limitations are not taught in either Ackay or Cohen”. This is not found persuasive.
As discussed in the modified rejection above, the combination of references teaches not only the same antibody as is instantly claimed, but also the underlying pathways and disease states implicated by chronic kidney disease. Ackay et al. primarily focuses on the proinflammatory effect of IL-33 in the cell and localizes this effect to the kidneys. Tonacci et al. takes a broader view of the IL-33/ST2 pathway and its implications on diabetic patients and found that increased IL-33 signaling worsened chronic kidney disease in patients. This sets up the framework for the inhibitory qualities of the anti-IL-33 antibody taught by Cohen et al., which would hamper the pathway in order to treat chronic kidney diseases by attenuating or inhibiting IL-33 mediated ST2 signaling and IL-33 mediated RAGE signaling. As such, the combination of references set forth a clear motivation for the use of the antibody to impede on the claimed pathway and treat chronic kidney diseases related to diabetic kidney disease.
As such, the rejection has been modified to render the instantly amended claims obvious.
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 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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SELAM BERHANE whose telephone number is (571)272-6138. The examiner can normally be reached Monday - Friday, 9-5.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Jeffrey Stucker can be reached at 571-272-0911. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/SELAM BERHANE/Examiner, Art Unit 1675
/AURORA M FONTAINHAS/Primary Examiner, Art Unit 1675