DETAILED ACTION
Status of Application, Amendments and/or Claims
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
The amendment of 12/17/25 has been entered in full. Claims 26-29 are amended. New claim 38 is added.
Claims 26-38 are pending and under consideration.
Information Disclosure Statement
The Information Disclosure Statement of 12/17/25 has been considered.
Withdrawn Objections and/or Rejections
The following page numbers refer to the previous Office Action (9/23/25).
The objection to the specification at page 2 is withdrawn in view of the amended title.
The rejection of claims 26-37 on the ground of nonstatutory double patenting at pages 7-9 as being unpatentable over claims 1-12 of U.S. Patent No. 11,384,143, issued 7/12/22, and further in view of Nakano et al (2009) is withdrawn in view of the terminal disclaimer naming the ‘143 patent filed 12/17/25 and approved by the USPTO.
The provisional rejection of claims 26-37 on the ground of nonstatutory double patenting at pages 9-11 as being unpatentable over claims 1-25 and 31-33 of copending application 17/708,660, filed 3/30/22 is withdrawn in view of the terminal disclaimer naming the ‘660 application filed 1/16/26 and approved by the USPTO.
The provisional rejection of claims 26-37 on the ground of nonstatutory double patenting at pages 11-13 as being unpatentable over claims 1-11 and 13-17 of copending application 17/991,880, filed 3/30/22 is withdrawn in view of the terminal disclaimer naming the ‘880 application filed 1/16/26 and approved by the USPTO.
Maintained Objections and/or Rejections
Note on Prior Art Rejection(s)
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 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.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102 of this title, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negatived 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 at the time any inventions covered therein were effectively filed 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 at the time a later invention was effectively filed 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 26-38 are rejected under 35 U.S.C. 103(a) as being unpatentable over Kakkar et al, U.S. Patent Application Publication 20170029499 (cited on a 1/18/23 IDS), and further in view of Nakano et al, 2009. Am J Kidney. 55: 21-30 (cited previously). This rejection was set forth at pages 3-6 of the 9/23/25 Office action for claims 26-37; Applicants’ addition of new claim 38 necessitates addition of this claim.
Applicants have amended independent claim 26 to replace “one monthly” administration with “subcutaneously at a monthly equivalent dose of 5 – 20 mg”. The specification teaches that the term “monthly equivalent dose” is “the calculated total dose administered per month, regardless of dose amount and dosage schedule” (¶ 314, published application). Claim 26 has further been amended to limit the cardiovascular (CV) morbidity and mortality that is treated to being selected from a group consisting of nonfatal myocardial infarction, nonfatal stroke, CV death and heat failure, a limitation that was previously present in dependent claim 29.
As such, claim 26 as amended encompasses a method of treating cardiovascular morbidity and mortality comprising administering ziltivekimab to a patient in need thereof; wherein the patient has chronic kidney disease (CKD) and atherosclerotic cardiovascular disease (ASCVD), and wherein the ziltivekimab is administered subcutaneously at a monthly equivalent dose of 5-20 mg, and wherein the CV morbidity and mortality is selected from a group consisting of nonfatal myocardial infarction, nonfatal stroke, CV death and heat failure. The instant application teaches that another name for ziltivekimab is MEDI5117 (¶ 167, page 28).
As set forth previously, the terms “morbidity” and “mortality” are not defined by the instant specification. The term “morbidity” is interpreted broadly as encompassing the presence of a disease or any symptoms thereof; and “mortality” is interpreted as “death”. Furthermore, the term “treating” is defined as “reducing or ameliorating a disorder, and/or signs or symptoms associated therewith, or slowing or halting the progression thereof” (¶ 83, page 15). Furthermore, one of the symptoms of CVD is death, and therefore “treating morbidity” also encompasses “treating mortality”. As such, both parts of the phrase “treating cardiovascular morbidity and mortality” encompasses reducing the mortality (death) resulting from CVD.
As set forth previously, Kakkar teaches methods of treating a hepcidin-mediated disorder by administering an IL-6 antagonist (¶ 6), and further wherein the hepcidin-mediated disorder is chronic kidney disease (¶ 15) and further wherein “[i]n some CKD embodiments is administered at a dose, on a schedule, and for a periods to reduce cardiovascular (CV) mortality as compared to age-matched and disease-matched historical controls” (¶ 18). Kakkar further teaches that the patient can have CKD and CVD (¶ 273). Kakkar teaches a definition of treating that is identical to that of the instant application quoted above (¶ 115). As such, the methods of treating a hepcidin-mediated disorder include reducing mortality, and thus the method reads on treating CV morbidity and mortality in a patient in need thereof, and wherein the patient has CKD. Kakkar further teaches that the IL-6 antagonist is an IL-6 antibody, and further that the antibody is MEDI5117 (¶ 192), which is another name for ziltivekimab as evidenced by the teaching of the instant application cited above. Kakkar further teaches that the IL-6 antagonist of the invention can be administered “once a month” (¶ 230).
With respect to the new limitation directed to administration, Kakkar further teaches that “In various subcutaneous embodiments … the IL-6 antagonist is administered … once a month” (¶ 230), and can be given in a “subcutaneous flat dose” that is 10 mg, 20 mg, or 10-20 mg (¶ 226), each of which is within the range newly recited in the claim.
With respect to the new limitation directed to treating CV morbidity and mortality that is selected from a group including CV death, this is met by the teachings of Kakker from ¶ 18 cited above regarding reducing CV mortality.
As such, Kakkar teaches a method meeting all of the limitations of claim 26 as amended, except that Kakkar does not specifically teach atherosclerosis as an embodiment of the CVD; i.e., Kakkar does not specify that the patients to be treated, which include those with CKD and CVD, include those wherein the CVD is atherosclerotic.
As set forth previously, Nakano teaches that CKD is “associated with increased risks of cardiovascular disease and death” (page 21). Nakano teaches that “[s]everal autopsy-based studies have shown a higher prevalence of arteriosclerotic lesions in individuals with CKD than those without CKD” and “patients with end-stage renal disease show more advanced atherosclerotic lesions with calcification in coronary arteries than the general population” (page 22). Nakano further teaches that “[t]his study showed a clear relationship between lower kidney function and severity of coronary atherosclerosis in autopsy samples in a general population”, “showing gradual progression of coronary atherosclerosis, even in individuals with moderate CKD” (page 27).
It would have been obvious to the person of ordinary skill in the art to take the method of treatment of a patient having CKD and CVD by administering MEDI5117 (ziltivekimab) subcutaneously at a monthly dose of 10-20 mg, including treating CV mortality (i.e. death) that is taught by Kakkar, and modify it to apply the treatment to a patient having CKD and CVD that is atherosclerotic as taught by Nakano. The person of ordinary skill in the art would have been motivated to make this change in order to apply the benefits (treatment and reduction of mortality) taught for a patient with CKD and CVD to a patient having CKD and atherosclerotic CVD as taught by Nakano. The person of ordinary skill in the art would have had a reasonable expectation of success in treating such patients because such a modified patient population merely represents a narrower but prior-art recognized subpopulation of the original patient population to be treated by Kakkar, and in the absence of any contraindication the skilled artisan would expect that the treatment that benefit the broader patient population to also benefit the narrower population, and furthermore because the co-morbidity (atherosclerotic CVD) is a disease related to the benefit of the treatment (reduction of CVD morbidity and mortality).
Claims 27 and 28 encompass a method of claim 26 wherein the ziltivekimab is administered subcutaneously and at 15 mg. Kakkar further teaches that IL-6 antagonist can be administered subcutaneously (¶ 53), and at 15 mg (¶ 225). It would have further been obvious to administer the antibody using such parameters when practicing the method of obvious over the teachings of Kakkar in view of Nakano described above for claim 26, because reduction to practice of a treatment method requires a route of administration and a dosage, and these are further taught by Kakkar as part of the treatment method.
Claim 29, as amended, now excludes the alternative directed to “heart failure”. Claim 29 as amended encompasses a method of claim 26 wherein the CV morbidity and mortality is selected from a group including CV death, which is the alternative over which parent claim 26 is rejected (see above). As such, claim 29 is obvious over the teachings of Kakkar in view of Nakano for the same reasons set forth for claim 26.
Claim 30 encompasses a method of claim 26 wherein the CV morbidity and mortality is heart failure. As such, these claims encompass treatment of heart failure in a patient in need thereof. Kakkar further teaches that the patient having CKD or CVD can have a history of heart failure (¶ 250), and Nakano further teaches that “Cardiac failure is more common in patients with advanced CKD, showing a prevalence of ~40%” (page 22). As such, it would further be obvious to apply the treatment method obvious over Kakkar in view of Nakano to a patient also having a history of heart failure, as such simply represents a further subpopulation of the patient population to be treated.
Claims 31-34 encompass a method of claim 26 wherein the patient has inflammation (claim 31) that is IL-6 mediated inflammation (claim 32), and wherein the inflammation is measured by C-reactive protein (CRP) levels (claim 33), and further wherein the patient has a CRP level greater than 2 mg/L, and wherein treatment is sufficient to reduce the level to 2 mg/L or less (claim 34). Kakkar further teaches that the method is for treating the chronic inflammation that contributes to mortality in CKD patients (¶ 249). Such inflammation is inherently IL-6 mediated as the administered antibody is an IL-6 antagonist antibody that results in reduction of the inflammation. Kakkar further teaches that increased inflammation is characterized by increased levels of CRP that are greater than 2 mg/mL (¶ 261) and that the amount of administered IL-6 antagonist that is “effective to neutralize inflammation reduces CRP to less than about 2 mg/L or less than about 0.2 mg/L” (¶ 262). As such, it would have further been obvious to apply the method obvious over the teachings of Kakkar in view of Nakano to a patient having such inflammation as measured by CRP.
Claims 35-37 limit the method of claim 31 by means of a further “wherein” clause.
In each claim, the wherein clause has been fully considered in context of the entire claim, but does not render the claimed method patentably distinct from a method taught by the prior art because it simply expresses the intended result of a process step positively recited. See MPEP 2111.04, which states that a "whereby clause in a method claim is not given weight when it simply expresses the intended result of a process step positively recited" (Hoffer v. Microsoft Corp., 405 F.3d 1326, 1329, 74 USPQ2d 1481, 1483 (Fed. Cir. 2005), quoting Minton v. Nat ’l Ass ’n of Securities Dealers, Inc., 336 F.3d 1373, 1381, 67 USPQ2d 1614, 1620 (Fed. Cir. 2003)). Specifically, in claims 35-37, the claims simply express the intended result (reduction of inflammation without immune suppression, as represented by absolute neutrophil count) of a process step positively recited (administering ziltivekimab to a patient having CKD and atherosclerotic CVD). As such, the method obvious over the teachings of Kakkar in view of Nakano set forth above for parent claims 26 and 31 also meets the limitations of claims 35-37.
New claim 38 encompasses a method of treating CV morbidity and mortality comprising administering ziltivekimab to a patient in need thereof, wherein the patient has stage 3-5 CKD, ASCVD, and inflammation, and has a CRP level of 2 mg/L or more, wherein said CV morbidity and mortality is selected from a group including HF, wherein said treatment reduces the atherosclerosis risk, and wherein the ziltivekimab is administered subcutaneously at a monthly equivalent dose of about 15 mg.
In claim 38, the “wherein” clause directed to reduction of atherosclerosis risk has been considered in context of the entire claim, but does not render the claimed method patentably distinct from a method taught by the prior art because it simply expresses the intended result of a process step positively recited. See above for claims 35-37. Specifically, in claim 38, the claim simply expresses the intended result (reduction of atherosclerosis risk) of a process step positively recited (administering ziltivekimab to a patient having stage 3-5 CKD, atherosclerotic CVD, inflammation and a CRP level of 2 m/L or more).
As such, new claim 38 encompasses a method of treating CV morbidity and mortality comprising administering ziltivekimab to a patient in need thereof, wherein the patient has stage 3-5 CKD, ASCVD, and inflammation, and has a CRP level of 2 mg/L or more, wherein said CV morbidity and mortality is selected from a group including HF, and wherein the ziltivekimab is administered subcutaneously at a monthly equivalent dose of about 15 mg. This is a narrower embodiment of independent claim 26.
The method obvious over the teachings of Kakkar in view Nakano is set forth above for claim 26. Kakkar further teaches that CKD may be stage 3, 4 or 5 (¶ 16). Kakkar further teaches the limitations directed to inflammation and a CRP level of 2/ mg/mL or more as set forth above for claims 32-33. A dose of “about 15” of ziltivekimab is indefinite (as set forth below in the section, “Claim Rejections – 35 USC 112(b)” but has been interpreted to encompass 10, 20 or 10-20 mg as taught by Kakkar (see above for claim 26). As such, it would have further been obvious to select a patient having CKD at a stage of 3, 4 or 5 as further taught by Kakkar and having inflammation and a CRP level of 2.0 mg/mL or greater also as taught Kakkar when practicing the method of claim 26 obvious over the teachings of Kakkar in view of Nakano set forth above, because such are envisioned as patients of the treatment method as taught by Kakkar.
Applicants’ arguments (12/17/25; page 6) as they pertain to the rejection have been fully considered but are not deemed to be persuasive for the following reasons.
In the response, Applicants argue that “[f]undamentally, Kakkar does not disclose or contain any experiments or actual data using ziltivekimab” and instead “merely discloses long laundry lists of many IL-6 antibodies and antagonists on top of other long laundry lists of disorders, dosing regimens, etc” (page 6). Applicants argue that the “[t]he skilled artisan cannot arrive at the present invention without undue experimentation because, as the Federal Circuit court has consistently recognized, the pharmaceutical sciences constitute an unpredictable art, wherein even small changes in dose, formulation, molecular structure, etc can lead to unexpected clinical outcomes, defeating any presumption of routine optimization or reasonable expectation of success” (pages 6-7). Applicants further argue that the secondary reference of Nakano does not cure the deficiencies of Kakkar (page 7). Applicants further that the rejection “arrives at the present invention” by reasoning based on “impermissible hindsight” (page 7).
Applicants’ arguments have been fully considered but are not found persuasive. Per MPEP 2121.I, “When the reference relied on expressly anticipates or makes obvious all of the elements of the claimed invention, the reference is presumed to be operable. Once such a reference is found, the burden is on applicant to rebut the presumption of operability.” While it is acknowledged that Kakkar does not disclose any experiments that specifically use the anti-IL-6 antibody ziltivekimab (aka MEDI5117), Kakkar does provide experimental results regarding use of an anti-IL-6 antibody to treat an animal model of a cardiorenal syndrome, characterized as a “secondary cardiac injury” resulting from “impaired cardiac function, which is a major contributor to mortality rates”, which develops following “chronic kidney disease” (Example 4, ¶ 403-416). While this is directed to an animal model, “An in vitro or in vivo animal model example in the specification, in effect, constitutes a "working example" if that example "correlates" with a disclosed or claimed method invention” (MPEP 2164.02). Thus, it is not found persuasive that the Kakkar does not provide any evidence in support of the claimed method of treatment.
Kakkar further expressly teaches MEDI5117 (ziltivekimab) as an exemplary IL-6 antagonist (¶ 23), having specificity for “human IL-6” (¶ 195), and an anti-IL-6 antibody that was known in the prior art, incorporating by reference the teachings of prior art US 20120034212 (cited on a 1/18/23 IDS in the application) (¶ 192), where it is termed “Antibody 18” and described as being “high affinity human” anti-IL-6 antibody that is “capable of blocking IL-6 binding to IL-6R” (¶ 535, Example 1). Therefore, it is not found persuasive that the teachings of Kakkar directed to ziltivekimab are directed solely to a laundry list of IL-6 antibodies and antagonists, but rather are directed to ziltivekimab being a specifically disclosed exemplary antibody having anti-human-IL-6 antagonist activity, which would be presumed enabling for use in a method of treatment of a human subject with an anti-IL-6 antibody.
In response to Applicants’ argument that the examiner's conclusion of obviousness is based upon improper hindsight reasoning, it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971). In the instant case, the rejection is based on the teachings of the references of Kakkar in view of Nakano, and thus only takes into account knowledge with which was within the level of ordinary skill at the time the claimed invention was made, and therefore is proper.
New rejections necessitated by Applicants’ amendment
Claim Rejections - 35 USC § 112(b)
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 38 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 pre-AIA the applicant regards as the invention.
Claim 38 is indefinite with regard to the recitation of “about 15 mg" due to the use of the term "about". Per MPEP 2173.05(b)(III)(A), “In determining the range encompassed by the term “about”, one must consider the context of the term as it is used in the specification and claims of the application”. In the instant case, the specification does not define the term, either with respect to dosages or generally, and instead merely uses the term in the same manner as the claim, e.g., at ¶ 16 (published application). The specification does not provide any guidance such that the skilled artisan would know which doses are encompassed by the claim. Thus, due to the use of the term "about", the claim is indefinite as to what degree of variation is encompassed; for example, "about 15" could encompass a range of 14.99 to 15.01, 14.9 to 15.1, 14.5 to 15.5, 14 to 16, or 10 to 20, to list several of the many alternate possibilities. For purposes of advancing prosecution, the term is interpreted as encompassing each of the alternate possibilities that the indefinite term reads upon.
Claim Rejections - 35 USC § 112(d)
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.-Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), fourth paragraph:
Subject to the [fifth paragraph of 35 U.S.C. 112 (pre-AIA )], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 30 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Per MPEP 608.01(n).III, “If the dependent claim does not comply with the requirements of 35 U.S.C. 112(d), the examiner should reject the dependent claim under 35 U.S.C. 112(d) rather than objecting to the claim” and “a dependent claim must be rejected under 35 U.S.C. 112(d) if it omits an element from the claim upon which it depends or it fails to add a limitation to the claim upon which it depends”.
Specifically, claim 30 limits “the cardiovascular morbidity and mortality” (CMM) of parent claim 29 to “heart failure”. However, parent claim 29 has been amended to remove heart failure from the recited group of CMM; as such parent claim 29 no longer encompasses the heart failure recited in dependent claim 30. Therefore, dependent claim 30 is of improper dependent form because it fails to further limit the subject matter of parent claim 29.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Conclusion
No claims are allowed.
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 mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ZACHARY C HOWARD whose telephone number is (571)272-2877. The examiner can normally be reached on Monday to Friday from 9 AM to 5 PM. If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Vanessa Ford, can be reached at telephone number (571) 272-0857. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/ZACHARY C HOWARD/Primary Examiner, Art Unit 1674