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 .
Claim Status
Claims 1-29 are cancelled.
Claims 30-36 are pending. Applicant’s amendment has necessitated modification of the existing rejection. Accordingly, this Action is FINAL.
Withdrawn rejections
Applicant's amendments and arguments filed 1/30/26 are acknowledged and have been fully considered. The Examiner has re-weighed all the evidence of record. Any rejection and/or objection not specifically addressed below is herein withdrawn.
The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set of rejections and/or objections presently being applied to the instant application.
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.
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.
.
Claims 30-36 are rejected under 35 U.S.C. 103 as being unpatentable over Zager et al (WO2017165692A1), as evidenced by Millipore Sigma (Hanks′ Balanced Salt solution, Millipore Sigma, [online] downloaded in March 2025 from: https://www.sigmaaldrich.com/US/en/product/sigma/h9269?srsltid=AfmBOopyEwIYD2TccQzP9fpZFytaBGEwemNO8bRmEGyoRT4VkauV1KLg; 7 pages; (Hereinafter Millipore Sigma), in view of Loniewski et al. (Kidney International (2014) 85, 529–535) and Crary et al. (Pediatr Blood Cancer 2011;56:615–619) and Tobe (US20020077580).
This application currently names joint inventors. In considering patentability of the claims under 35 U.S.C. 103, the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were made absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and invention dates of each claim that was not commonly owned at the time a later invention was made in order for the examiner to consider the applicability of 35 U.S.C. 103(c) and potential 35 U.S.C. 102(e), (f) or (g) prior art under 35 U.S.C. 103.
Applicant claims, for example:
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Claim interpretation: The limitation of “suitable for intravenous use in humans” only requires the ability to so perform.
Level of Ordinary Skill in the Art
(MPEP 2141.03)
MPEP 2141.03 (I) states: “The “hypothetical ‘person having ordinary skill in the art’ to which the claimed subject matter pertains would, of necessity have the capability of understanding the scientific and engineering principles applicable to the pertinent art.” Ex parte Hiyamizu, 10 USPQ2d 1393, 1394 (Bd. Pat. App. & Inter. 1988). The level of skill is that of a medical/pharmaceutical kidney research scientist, as is the case here, then one can assume comfortably that such an educated artisan will draw conventional ideas from kidney disorder diagnosis and treatments, kidney disease treatments, pharmaceutical formulations and kidney physiology and— without being told to do so.
In addition, the prior art itself reflects an appropriate level (MPEP 2141.03(II)).
Determination of the scope and content of the prior art
(MPEP 2141.01)
Regarding claims 30 and 34, Zager teaches “A method including: administering to an organ, a therapeutically effective amount of a formulation including (i) a source of iron and (ii) a tin salt or a cobalt salt, wherein administration of the therapeutically effective amount of the formulation to the organ protects the organ without causing injury to the organ.” (page 50 embodiment 93) wherein the organ is kidney (page 51 embodiment 102) wherein the composition to be administered comprises Iron sucrose and tin protoporphyrin (para 177-178, 189). Zager teach for human administration [0143, 0149]. Zager teaches that the methods protect the kidney [0158] and mitigate acute kidney injury ([0013, 0178]; Figure 6), ostensibly in patients in need of kidney protection, where the renal dysfunction of the patients can be accompanied by metabolic acidosis [0156]. Zager also teaches embodiments that are “prepared for intravenous administration” (para 135) wherein “for injection, formulations can be formulated as aqueous solutions, such as in buffers including Hanks' solution that contains stabilizing agents (para 135). Evidentiary reference Millipore Sigma provides the evidence that Hank’s solution comprises sodium bicarbonate (page 1). Zager also teaches a pharmaceutically acceptable carrier (para 127) and to employ buffering agents [0127]. Thus, the pharmaceutically acceptable carrier of Zager
makes the aqueous pharmaceutical composition suitable for intravenous use in humans.
Regarding claim 31, Zager teaches aqueous solutions and sterile water (para 135).
Regarding claim 32, Zager teaches phosphate buffered saline (PBS) as vehicle (178), which is interpreted as a pharmaceutically acceptable carrier.
Regarding claim 33, Zager teaches that: “A saccharide-metal complex can include iron in the (II) or (Ill) oxidation state complexed with anions of the saccharide.” [0048].
Regarding claim 36, Zager teaches “In particular embodiments, organs are protected from injury during transplant. The formulations can be administered (i) to an organ donor before organ isolation from the donor; (ii) to the isolated organ before transplantation, and/or (iii) to the organ transplant recipient. This method of use can apply to any organ capable of transplant from one individual subject to a second individual subject.” (para 155). Zager reports: “combined iron-sucrose + Sn-protoporphyrin conferred marked protection” [0011].
Regarding claims 30 and 36, Loniewski et al. teaches NaHCO3 in nephrology and that individuals with CKD have a reduced number of functioning nephrons, obligating more acid excretion per remaining nephron and teaches bicarbonate therapy for prevention of CKD progression (Title; Abstract; page 529, right column; Page 534, Table 5). Loniewski et al. teach that it is known to employ sodium bicarbonate to treat metabolic acidosis (Page 529, right column NaHCO3 in Nephrology) and the metabolic acidosis can be due to CKD (Page 530, left column Pathophysiological background).
Regarding claims 30 and 34, Tobe teach sodium bicarbonate dialysis compositions (Claim 1) for the treatment of acute renal failure (Claim 7) and metabolic acidosis (Claim 12).
Regarding claim 35, Crary et al. teach that it is well-known in the art to use intravenous (IV) iron sucrose formulations to treat CKD, has a favorable safety profile and was approved by the FDA in 2000 for dialysis dependent chronic kidney disease (Page 615, left column 2nd paragraph).
Ascertainment of the difference between the prior art and the claims
(MPEP 2141.02) and Finding of prima facie obviousness
Rational and Motivation (MPEP 2142-2143)
The difference between the instant application and Zager is that Zager do not expressly teach an embodiment with sodium bicarbonate or using both Fe(II) and Fe(III) and administer the formulation by intravenous injection to a patient undergoing an organ transplantation or chronic kidney disease. This deficiency in Zager is cured by Loniewski et al., Tobe and Crary et al.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to use sodium bicarbonate, as suggested by Loniewski et al. and Tobe, and both Fe(II) and Fe(III) in the formulation of Zager and administer the formulation by intravenous injection to a patient undergoing an organ transplantation or treat chronic kidney disease, as suggested by Crary et al., and produce the instant invention.
One of ordinary skill in the art would have been motivated to do this because of the following rationale. First, Zager teach iron-sucrose formulations. Secondly Crary et al. teach that it is well-known that patients suffering with treating chronic kidney disease are treated with IV iron-sucrose, which is approved by the FDA and has a favorable safety profile. Thirdly, Zager teach and suggest employing buffer agents [0127] and expressly teach Hanks’ solution [0135], which contains sodium bicarbonate, a well-known buffer agent by the ordinary artisan. Zager also teaches treating metabolic acidosis, which is acidification of the blood [0156]. And the ordinary artisan is already aware that sodium bicarbonate can be used to treat metabolic acidosis as well as chronic kidney disease through the teachings of Loniewski et al. and Tobe. Consequently, it is obvious to employ sodium bicarbonate in the formulation of Zager as both as a buffer agent and as an agent to treat metabolic acidosis/CKD with a reasonable expectation of success. With regard to the iron ions, Zager teaches that either Fe(II) or Fe(III) are useful, which renders obvious their combined use for the same purpose. "The combination of familiar elements according to known methods is likely to be obvious when it does no more than yield predictable results." KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398, 417 (2007). See also See MPEP 2144.06(I) COMBINING EQUIVALENTS KNOWN FOR THE SAME PURPOSE “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 which is to be used for the very same purpose.” In re Susi, 58 CCPA 1074, 1079--80, 440 F.2d 442,445 (1971); In re Crockett, 47 CCPA 1018, 1020-21, 279 F.2d 274, 276-77 (1960). As explained in Crockett, the 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)). Accordingly, it is obvious to combine both Fe(II) and Fe(III) in the formulation of Zager with a reasonable expectation of success. As noted above, Zager teaches protection of organs during transplantation, which then renders obvious administration of the formulation with buffering sodium bicarbonate and both Fe(II) and Fe(III) by intravenous injection to a patient undergoing an organ transplantation with a reasonable expectation of success for the desirable function of protecting the organ.
Consequently, the ordinary artisan would have a reasonable expectation of success in treating chronic kidney disease or a patient undergoing an organ transplantation with the iron sucrose/sodium bicarbonate formulation of Zager as modified by Loniewski et al., Tobe and Crary et al. in the absence of evidence to the contrary.
In light of the forgoing discussion, the Examiner concludes that the subject matter defined by the instant claims would have been obvious within the meaning of 35 USC 103.
From the combined teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the combined references, especially in the absence of evidence to the contrary.
Response to Arguments:
Applicant’s arguments filed 1/30/26 have been carefully considered but are persuasive.
On page 5 of remarks, Applicant states: “The present inventors discovered, however, that tin protoporphyrin when stored at or near physiological pH may undergo dimerization and precipitation. See Spec., P 38. The present inventors discovered that this dimerization could be reduced and/or avoided by storing the tin protoporphyrin at a lower pH level… Therefore, the present inventors perceived the need to modify one or more of the components to address the pH issue. Neither the problem with dimerization or the problem of using a lower-pH Sn PP were known at the time of the invention.” Respectfully, the Examiner cannot agree because it has been known since at least 1991 that tin protoporphyrin in aqueous media exists as a mixture of monomeric and dimeric species where the dimers prevail as the pH is decreased (Abstract of: Reddi et al. J Photochem Photobiol B. 1991;8(2):159-67; 1 page).
On page 5 of remarks, Applicant argues: “It should be noted that the term "injection" is used throughout Zager in a manner that does not suggest a composition that is suitable for intravenous use in humans.” Respectfully, the Examiner has a different perspective. Zager expressly teaches formulation for intravenous administration [0134-0135] and state: “Particular kits provide materials to administer formulations through intravenous administration.” [0145] Zager expressly teach administration to humans [0143, 0149]. The only reasonable conclusion is that Zager teach and suggest aqueous formulations suitable for intravenous use in humans. Applicant asserts that Hank’s balanced salt solution is a laboratory buffer but not for human use. Respectfully, the Examiner does not agree because while those typical uses are noted, the art also teaches Hank’s solution for intravenous use. See US20030232738 teaching in claim 22 “wherein said pharmaceutically acceptable delivery vehicle is selected from the group consisting of water, phosphate buffered saline, Ringer's solution, dextrose solution, serum-containing solutions, Hank's solution, other aqueous physiologically balanced solutions” and claim 32 “wherein said step of administering is by a route of administration selected from the group consisting of intradermal, intravenous”. Consequently, the art teaches that Hank’s solution is pharmaceutically acceptable for intravenous delivery. Furthermore, the references of Loniewski et al. and Tobe are provided for teaching sodium bicarbonate to add to the composition of Zager. Respectfully, Applicant’s arguments are not persuasive.
On page 6 of remarks, Applicant asserts: “Loniewski is cited for its teaching that sodium bicarbonate is used to treat metabolic acidosis. However, the claimed composition is used for a different purpose than treating metabolic acidosis. That is, the current composition is used to reduce post operative complications from surgeries such as cardiac bypass surgery.” And: “Tobe teaches a dialysis composition. There is no suggestion that one would combine a dialysis composition with SnPP and FeS as required by the claims.” Respectfully, the Examiner cannot agree because “cardiac bypass surgery” is not a claimed limitation; rather CKD and organ transplantation are claimed conditions for the patient. Zager teaches the organ transplantation population and Loniewski, Tobe and Crary render obvious treating the CKD patient population. Crary is relied upon as cited in the rejection. Respectfully, Applicant’s arguments are not persuasive.
Summary
MPEP 2141 III states: “The proper analysis is whether the claimed invention would have been obvious to one of ordinary skill in the art after consideration of all the facts.” Respectfully, after review of all the facts, Applicant’s arguments are not persuasive. The Examiner has reached a determination that the instant claims are not patentable in view of the preponderance of evidence and consideration of all the facts, which is more convincing than the evidence which has been offered in opposition to it.
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 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 ERNST V ARNOLD whose telephone number is (571)272-8509. The examiner can normally be reached M-F 7-3:30.
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/ERNST V ARNOLD/Primary Examiner, Art Unit 1613