DETAILED ACTION
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 .
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on June 15, 2025 has been entered.
Status of Claims
Claims 238-250 and 252 are pending. Claim 238 is amended. Claim 251 and 253 are canceled.
Previous Rejections
Rejections and/or objections not reiterated from previous office actions are hereby withdrawn as are those rejections and/or objections expressly stated to be withdrawn. The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application.
Rejections Withdrawn
Claim Rejections - 35 USC § 103
In light of the amendments to the claims the rejection of claims 238-250 and 252 under 35 U.S.C. 103 as being unpatentable over Klaerner et al. US 2016/0074430 (2/26/2015)(6/15/2021 IDS) is withdrawn.
New Rejections
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 of this title, 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(a) 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.
This application currently names joint inventors. In considering patentability of the claims under 35 U.S.C. 103(a), 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(a).
Claims 238-250 and 252 are rejected under 35 U.S.C. 103 as being unpatentable over Klaerner et al. US 2016/0074430 (2/26/2015)(6/15/2021 IDS) in light of Stanek et al. US 2004/0028803 (2/12/2004).
Klaerner et al. (Klaerner) teaches nonabsorbable, crosslinked polymers containing free amine moieties for use in the treatment of metabolic acidosis at a dose of 0.5 g/day to about 20 g/day to achieve or maintain a serum bicarbonate level of at least about 20 mEq/L. Klaerner teaches a method of treating metabolic acidosis in an adult human patient by increasing the patient serum bicarbonate of at least about 20 mEq/L by administering a dose of 0.5 g/day to about 20 g/day. (See [0028]). Klaerner teaches an embodiment in which the dose will be about 3 g/day as called for in instant claim 238. (See [0114]). This method taught by Klaerner thus reads on the method called for in instant claim 238. The at least about 20 mEq/L taught by Klaerner overlaps with the at least 3 mEq/L called for in instant claim 241. Klaerner teaches that the polymers are administered once or twice per day. (See [0122]). Administration twice per day is called for in instant claim 238.
Klaerner teaches that its nonabsorbable composition has the capacity to absorb protons and remove them from the patient as called for in instant claim 238. (See Abstract). In Klaerner claim 2 it expressly teaches that its crosslinked amine polymer has an equilibrium swelling ratio in deionized water of about 1.5 or less, which overlaps with the about 2 or less called for in instant claim 238 and the about 1.5 or less called for in instant claim 244.
Claim 240 requires that the increase in the patient’s serum bicarbonate level is at least 1 mEq/L over 15 days of treatment. (See [0114]). As described above, Klaerner teaches an embodiment in which 3 g/day is administered. Since the same amount of polymer is administered, it would necessarily result in the same increase in serum bicarbonate as that taught by Klaerner. In Figure 1A Klaerner teaches that its method enables clinically meaningful increase in serum bicarbonate of 3 mEq/L. This is at least 1 mEq/L as called for instant claim 240.
Klaerner also teaches patients with chronic kidney diseases as called for in instant claim 242. (See [0023], [0034], [0212] and [0214]). The patient’s serum bicarbonate level prior to treatment is less than 22 mEq/L which overlaps with the less than 18 mEq/L prior to treatment called for in instant claim 239. (See [0003]).
Klaemer teaches a chloride ion to phosphate ion binding molar ratio of at least 0.35:1 which overlaps with the at least 0.5 to 1 called for in instant claim 245. (See [0036] and [0039]). Klaemer teaches a chloride ion binding capacity of at least 5 mmol/g which overlaps with the at least 10 mmol/g called for in instant claim 246 and the at least 2.5 mEq/g called for in instant claim 243. (See [0042-0043]). Klaemer teaches a proton binding capacity of at least 5 mmol/g which overlaps with the at least 10 mmol/g called for in instant claim 246. (See [0042-0043]).
Klaerner teaches highly crosslinked aliphatic amine polymers in its claim 16 which have the same formula as that of Formula 2b in instant claim 238. (Klaerner refers to its formula in claim 15 as Formula 2).
Additionally, and more specifically, Klaerner teaches highly crosslinked aliphatic amine polymers that result from the polymerization of allylamine hydrochloride and N,N’-diallyl-1, 3-diaminopropane dihydrochloride. The polymer resulting from the polymerization of these monomers is described in Example 1 of the specification as being effective in treating acidosis in an adenine-induced model of neuropathy in rats in Example 1 on page 127 of the instant specification. Thus, Klaerner teaches that the crosslinked amine polymer comprises the residue of 1,3-bis(allylamino)propane as called for in instant claims 249 and 250. This corresponds to Formula 2b in claim 238 when there are two allyl moieties as called for in instant claim 248 and wherein m and z are independently 0-3 and n is 0 or 1 as called for in instant claim 247.
The crosslinking agent can be 1,2-dichloroethane as called for in instant claims 238 and 251. (See [0130]). Klaerner teaches that 1,2-dichloroethane is a suitable crosslinking agent and exemplifies with dichloropropane a ratio of dichloropropane to polymer bead in excess of 3mL dichloropropane to 1 g of polymer. (See [370]). While Klaerner exemplifies with dichloropropane a ratio of dichloropropane to polymer bead in excess of 3mL dichloroprane to 1 g of polymer, Klaener expressly teaches that 1,2-dichloroethane is a suitable crosslinking agent as well. Furthermore, Klaener teaches the equivalence of 1,2-dichloroethane with dichloropropane as solvents that are miscible with the crosslinker and immiscible with the swelling agent. (See [0145]).
In light of Klaener’s teaching of the equivalent of 1,2-dichloroethane with dichloropropane as solvents for crosslinking, it would be obvious for one of ordinary skill in the art to just replace dichloropropane with 1,2-dichloroethane and follow the example with a ratio of 1,2-dichloroethane to polymer bead in excess of 3 mL 1,2-dichloroethane to 1 g of polymer as called for in instant claim 238.
The composition comprising the proton-binding amine polymer can be formulated for oral administration in the dosage form of tablets as called for in instant claim 252.
Klaerner teaches that its compositions are very effective in treating metabolic acidosis. (See Abstract, claims, Embodiments 75 and 76 and throughout).
Klaerner teaches the use of only dichloroethane for the secondary crosslinking of the amine polymer, but does not teach a step of adding water after using the dichloroethane for the secondary crosslinking of the amine polymer. This deficiency is made up for with the teachings of Stanek et al.
Stanek et al. (Stanek) teaches a method for alkylating cross-linked polymers containing N- or amino, or ammonium groups. (See Abstract). Stanek teaches that the polymers that are obtained by polymerization and cross-linking are optionally deprotonated in water by adding a base and water. (See claim 1 ).
This step of adding water following the use of just dichloroethane (neat dichloroethane) is called for in instant claim 238.
It would have been prima facie obvious for one of ordinary skill in the art making the Klaerner composition before the earliest effective filing date to use the taught nonabsorbable, crosslinked polymers containing free amine moieties for use in the treatment of metabolic acidosis at a dose of 0.5 g/day to about 20 g/day to a patient with a serum bicarbonate level of less than 17 mEq/L administered twice a day to achieve or maintain a serum bicarbonate level of at least about 20 mEq/Lthem to treat metabolic acidosis because it would have been obvious to one of ordinary skill in the art to try any of the specifically taught pharmaceutical agents as a person with ordinary skill has good reason to pursue known options within his or her technical grasp. Note: MPEP 2141 KSR International CO. v. Teleflex Inc. 82 USPQ 2d 1385 (Supreme Court 2007). The selection of a specific drug is considered prima facie obvious depending on the desired condition/symptoms to be treated.
It would have been prima facie obvious for one of ordinary skill in the art making the Klaerner composition before the earliest effective filing date to add water and a base as taught by Stanek following the step of using just dichloroethane in order to deprotonate the polymer and allow the polymer to reprotonate from the acid present int eh metabolic acidosis in the process of treatment of metabolic acidosis as taught by Stanek.
Response to Arguments
Applicants’ arguments of April 18, 2025, have been fully considered and are found to be partly persuasive in light of the amendments to the claims.
Applicants note the amendments to the claims and assert that the present amendment further clarifies that the improved properties result from a specific secondary crosslinking step that is not taught by Klaerner. Applicants assert that the secondary crosslinking agent is DCE and the present specification discloses that DCE acts as a dispersant as well as a cross-linking agent, and provides a self-limiting effect on the secondary crosslinking.
Applicants assert that Klaerner fails to teach or suggest using neat DCE followed by the step of adding water wherein the ratio of DCE to polymer bead is in excel of 3 mL to 1 g of polymer.
Applicants assert that proton-binding, crosslinked amino polymers comprising the residue of an amine corresponding to Formula 2b exhibit an unexpected rapid increase in serum bicarbonate levels in human patients. Klaerner does not disclose or suggest that the recited polymers would rapidly increase serum bicarbonate levels by at least 1 mEq/L within 72 hours in an adult patient by administering just about 3 grams of the recited composition administered twice per day.
Applicants’ obviousness arguments have been carefully reviewed and are found to be only partly persuasive in light of the amendments to the claims. Applicant’s assertion that Klaerner fails to teach or suggest using neat DCE followed by the step of adding water is found to be sufficiently persuasive, and the rejection has been withdrawn above.
However, Applicants’ assertion that the present amendment further clarifies that the improved properties result from a specific secondary crosslinking step that is not taught by Klaerner is not found to be persuasive. There is no such disclosure in the language of the amended claims, and Applicants are pointing to the specification for disclosure that is entirely absent from the claims.
Neat DCE is found in the language of the claims. The step of adding water is found in the language of the claims. However, nowhere in the language of the amended claims is found any disclosure that that DCE acts as a dispersant as well as a cross-linking agent, and provides a self-limiting effect on the secondary crosslinking.
The language of the claims is met by the newly applied combination of prior art presented in the new rejection above. Namely, it would have been prima facie obvious for one of ordinary skill in the art making the Klaerner composition before the earliest effective filing date to add water and a base as taught by Stanek following the step of using just dichloroethane in order to deprotonate the polymer and allow the polymer to reprotonate from the acid present in the metabolic acidosis in the process of treatment of metabolic acidosis as taught by Stanek.
With respect to Appellants’ assertion of unexpected results, the property of increasing serum bicarbonate levels still does not appear to be all that unexpected given that Klaerner expressly teaches that its composition increases serum bicarbonate levels. While Klaemer may not specifically disclose that the recited polymers would rapidly increase serum bicarbonate levels by at least 1 mEq/L within 72 hours in an adult patient by administering just about 3 grams of the recited composition administered twice per day, the suggestion and teaching that its composition increases serum bicarbonate levels and its express teaching that the composition may be administered twice per day does suggest the overall unexpected result, though the specifics may not be recited.
Additionally, Klaerner states that a therapeutically effective dose of its crosslinked polymers will depend on the disease being treated, the capacity of the polymer itself and the intended effect. Therefore Klaerner appears to recognize that its polymer has the capacity to increase serum bicarbonate levels more quickly or even more slowly but that it will depend on what the therapeutic goals of the patient it is being administered to are.
See MPEP 716.02(e). The teachings of the prior art are consistent with expected beneficial results. Expected beneficial results are more indicative of obviousness than of unobviousness. “Expected beneficial results are evidence of obviousness of a claimed invention, just as unexpected results are evidence of unobviousness thereof.” In re Gershon, 372 F2d 535, 538, 152 USPQ 602, 604 (CCPA 1967)(resultant decrease of dental enamel solubility accomplished by adding an acidic buffering agent to a fluoride containing dentrifice was expected based on the teaching of the prior art). Where the unexpected properties of a claimed invention are not shown to have a significance equal to or greater than the expected properties, the evidence of unexpected properties may not be sufficient to rebut the evidence of obviousness. In re Nolan, 553 F.2d 1261, 1267, 193 USPQ 641, 645 (CCPA 1977). MPEP 716.02(c).
The submission of objective evidence of patentability does not mandate a conclusion of patentability in and of itself. In re Chupp, 816 F.2d 643, 2 USPQ2d 1437 (Fed. Cir. 1987). Facts established by rebuttal evidence must be evaluated along with the facts on which the conclusion of a prima facie case was reached, not against the conclusion itself. In re Eli Lilly, 902 F.2d 943, 14 USPQ2d 1741 (Fed. Cir. 1990). MPEP 716.01(d).
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SARAH CHICKOS whose telephone number is (571)270-3884. The examiner can normally be reached on M-F 9-6.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, David Blanchard can be reached on 571-272-0827. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/SARAH CHICKOS/
Examiner, Art Unit 1619
/DAVID J BLANCHARD/Supervisory Patent Examiner, Art Unit 1619