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 .
Continued Examination Under 37 CFR 1.114
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 07/29/2025 has been entered. Claims 1-30 are previously cancelled. Claim 31 has been amended, and claims 31-37 remain pending in the application.
Status of Objections and Rejections
All objections and rejections from the previous office action are withdrawn in view of Applicant's amendment.
New grounds of rejection under 35 U.S.C. 103 are necessitated by the amendments.
New grounds of rejection under non-statutory double patenting are necessitated by the amendments.
A new effective filing date of the instant claims is necessitated by the amendments.
Priority
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. Applicant has not complied with one or more conditions for receiving the benefit of an earlier filing date under 35 U.S.C. 112(a) as follows:
The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of 35 U.S.C. 112(a) or the first paragraph of pre-AIA 35 U.S.C. 112, except for the best mode requirement. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994).
The disclosure of the prior-filed application, Application No. 61/831,445, fails to provide adequate support or enablement in the manner provided by 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph for one or more claims of this application. Amended claim 31 recites “residues of (a) 2-Propen-1-ylamine or a salt thereof and (b) 1,3-Bis(allylamino)propane or a salt thereof” which is not present in the disclosure of Application No. 61/831,445. Therefore claim 31 will receive the effective filing date of parent Application No. 14/311,852 of 06/23/2014. Claims 32-37 likewise will receive the effective filing date of 06/23/2014 due to dependency upon claim 31.
Response to Arguments
Applicant's arguments, see pages 4-7, filed 07/29/2025, with respect to the rejections of claims 31-37, under 35 U.S.C. 103, have been fully considered but they are not persuasive.
Applicant argues (pp. 5-6 of remarks) that Connor does not teach the polymer of step (1) in claim 31.
Applicant’s arguments have been considered but are moot because the new ground of rejection does not rely on any reference applied in the prior rejection of record for any teaching or matter specifically challenged in the argument. Connor et al. has been replaced with Bianchi et al. (US 20100183732 A1) as the primary reference to support the rejection of this claim limitation.
Applicant argues (p. 5, para. 3 and p. 6, para. 2 of the remarks) that the Action (01/29/2025) fails to show that Connor teaches the specific initial SIB concentrations, pH value, and final polymer concentration to be result-effective variables for determining chloride to phosphate specificity and selectivity in testing for the effectiveness of the non-absorbable polymers.
The Examiner respectfully disagrees.
Bianchi is now the primary reference in place of Connor and teaches a polymer assay using the polymer of amended claim 31, step 1 ([0142][0148]). Bianchi is in the field of amine-based phosphate-binding polymers intended for use in the gastrointestinal tract and expressly teaches polymers designed to bind phosphate in the GI tract as part of hyperphosphatemia treatment ([0005]). However, Bianchi measures the phosphate-binding capacity of Sevelamer using an assay at a neutral pH of 7 in order to accommodate ion chromatography conditions for repeatability and precision (Mazzeo, fully incorporated by reference, “A phosphate binding assay for sevelamer hydrochloride by ion chromatography,” p. 915, col. 1, ll. 3-4; 1998). The instant disclosure claims that “The SIB buffer contains concentrations of chloride, phosphate and pH that are present in the human duodenum and upper gastrointestinal tract” (Paragraph [0095] of US 20220096534 A1), and then cites reference Fordtran et al. to conclude that the claimed specific SIB concentrations and pH are “an effective measure of the selectivity of chloride binding compared to phosphate binding by a polymer” ([0095]). The pH of the proximal small intestine has been extensively documented in the art for decades and constitutes background physiological knowledge, not a discovery unique to applicant. Fordtran simply summarizes long-established data showing that the post-gastric duodenum of the small intestines routinely exhibits pH values between approximately 4.0-8.0 (p. 510, pH, Fig. 7), with values around 5.3-5.6 immediately after gastric emptying, and this information would have been readily available to one of ordinary skill in the art. The duodenum is a well-recognized component of the GI tract, and because Bianchi addresses GI-active polyamine binders, Fordtran’s duodenal pH data is directly relevant background knowledge that a POSITA would naturally consider when evaluating the physiological environment in which such polymers operate.
Secondary reference, Connor (US 20100029897 A1), aims to assess the phosphate-binding capacity of sevelamer using an assay that “is designed to mimic the milieu of a portion of the GI tract after ingestion of a meal (Emphasis added), preferably the portion of the GI tract in which the polymer will be binding the majority of target ion” ([0050]). Connor also teaches that polyamine phosphate binders become increasingly protonated as pH decreases ([0048]), and this protonation directly increases anion binding affinity.
Finally, another reference, Swearingen (“Determination of the binding parameter constants of Renagel® capsules and tablets utilizing the Langmuir approximation at various pH by ion chromatography”; 2002), teaches evaluating anion-binding behavior across multiple pH values, including acidic pH ranges, and demonstrates that changing pH is a routine and expected experimental parameter for differentiating relative anion binding in sevelamer testing. Swearingen confirms that examining pH points such as 5.5 is standard practice when assessing polymers whose binding is protonation-dependent, and states that “it has also been shown that there are more protonated amines at pH 5.5 than at pH 7.0” (p. 200, col. 2, ll. 11-13). Thus, in light of Bianchi’s GI context, Fordtran’s physiological data, Connor’s chemical rationale, and Swearingen’s routine multi-pH level testing, a POSITA before the effective filing date of the claimed invention would have adjusted the pH of the buffer solution from 7 to 5.5 in order to test phosphate binding under acidic intestinal conditions for maximum binding(See MPEP 2143(I)(C)).
In response to the specific concentrations of the other buffer components, the teachings of Mazzeo further reinforce them to be result-effective variables. Bianchi fully incorporates Mazzeo by reference as the guide for producing the phosphate binding assay ([0142]). Mazzeo explains in its “Results and Discussion” section (pp. 914-915) that pH, ionic strength, phosphate speciation, and buffer identify are interdependent variables, and that when pH is altered, corresponding adjustments in buffer composition (e.g. MES concentration), phosphate salt, and ionic strength must be made to maintain measurable equilibrium and ion chromatographic detectability. Mazzeo demonstrates that buffer ionic strength, phosphate concentration, polymer assay loading, dilution factors, and pH are routinely adjusted in phosphate-binding and ion-chromatographic assays to match analytical needs and physiological models.
Mazzeo teaches 20.0 mM KH2PO4, 100 mM BES, and 80 mM NaCl is prepared with a pH of the solution of 6.95–7.05 into which sevelamer is added. Mazzeo fails to teach the claimed NaH2PO4 and MES buffer, however, It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have substituted BES with MES as taught by Connor at a pH of 5.5 ([00245]) since they are known equivalents as Good’s buffers that achieve the common purpose of assay stabilization (See MPEP 2143(I)(B)). Connor explains that “100 mM BES, pKa 7.1, was chosen to hold the pH at 7.0,” (page 915, columns 1-2), and therefore use of MES with a pKa of 6.1 would be a more appropriate stabilizer at the pH of 5.5. KH2PO4 and NaH2PO4 are known equivalents for supplying phosphate ions and are therefore interchangeable for use in the assay (MPEP 2144.06(II)). Likewise, selecting the appropriate final polymer concentration after the addition of the SIB buffer is another result-effective variable subject to routine optimization to set the sample in an optimal detection range for a desired signal on the ion chromatograph produced from a linear standard calibration (Mazzeo, p. 915, last para.). Bianchi already creates a final volume by mixing a polymer with a buffer before testing and it would have obvious to one of ordinary skill in the art to choose a polymer concentration that would yield more accurate and precise results (See MPEP 2144.05(II)).
Taken together, these references: Bianchi, Fordtran, Connor, Mazzeo, and Swearingen, demonstrate that the selection of pH 5.5, initial buffer concentrations, and final assay polymer concentration is not inventive insight, but a predictable application of (a) known GI physiology, (b) known polymer protonation chemistry, and (c) known assay-optimization principles. Accordingly, applicant’s arguments are not persuasive.
Applicant argues that “The Action further asserts that it would have been obvious to have modified Cooper with a pH of 6.5 to a pH of 5.5, stating that "[!]lowering pH would help 'to mimic the conditions of use of a phosphate binding polymer in a GI tract' (Connor, column 49, lines 7-8)." However, intestinal pH ranges between 6 and 9. Accordingly, a rationale is not articulated for why one would be motivated to lower the pH”.
The Examiner respectfully disagrees.
Connor discloses that "GI simulant" refers herein to a preparation that is designed to mimic the milieu of a portion of the GI tract after ingestion of a meal (Emphasis added), preferably the portion of the GI tract in which the polymer will be binding the majority of target ion” ([0050]). As discussed above, Swearingen confirms that examining pH points such as 5.5 is standard practice when assessing polymers whose binding is protonation-dependent, and states that “it has also been shown that there are more protonated amines at pH 5.5 than at pH 7.0” (p. 200, col. 2, ll. 11-13). Additionally, Applicant’s own reference, Fordtran, Fig. 7 shows that intestinal pH ranges between about 4 and 8. The polymer taught by primary reference is protonation-dependent, and therefore, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have adjusted the pH of the buffer solution from 7 to 5.5 so as to assess the efficacy of the drug by mimicking the milieu of a portion of the GI tract after ingestion of a meal in the intestines (See MPEP 2143(I)(C)).
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 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.
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.
Claims 31, 32 and 37 are rejected under 35 U.S.C. 103 as being unpatentable over Bianchi et al. (US 20100183732 A1) and Mazzeo (“A phosphate binding assay for sevelamer hydrochloride by
ion chromatography”; 1998; fully incorporated by reference) in view of Connor et. al. (US 20100029897 A1), Cooper et. al. (US 20100234309 A1), Swearingen et al. (“Determination of the binding parameter constants of Renagel® capsules and tablets utilizing the Langmuir approximation at various pH by ion chromatography”; 2002), and Liu et al. (US 20090186093 A1).
Regarding claim 31, Bianchi teaches a Simulated Small Intestine Inorganic Buffer (SIB) assay (“Phosphate binding assay,” wherein “phosphate-binding polymers are provided for removing phosphate from the gastrointestinal tract by oral administration”; Bianchi, [0142]; [0005]) comprising the steps of:
providing a proton-binding (Phosphate binders include organic polymers that act as ion
exchange resins; Bianchi, [0008]), crosslinked amine polymer (cross-linked poly(allylamine) polymers or salts; Bianchi, Abstract) comprising the residues of (a) 2-Propen-1-ylamine or a salt thereof and (b) 1,3-Bis(allylamino)propane or a salt thereof (“Allylamine…was added dropwise…and 1,3-bis-allylamino-2-propanol dihydrochloride (IV)…were added,” wherein a polymerized mixture naturally creates a residue including both compounds; Bianchi, [0148]);
2) adding SIB buffer comprising NaCI to the amine polymer (“A stock phosphate solution containing NaCl was prepared,” wherein “samples of sevelamer hydrochloride (135–141 mg) were weighed into a tared, 125 ml wide-mouthed plastic bottle, to which 100 ml of 20 mM phosphate stock solution was added”; Mazzeo, p. 912, col. 1, 2.3 Sample preparation, ll. 1-3; p. 912, col. 2, para. 2, ll. 1-5)(Paragraph [0142] of Bianchi explains that the phosphate binding assay was carried out according to Mazzeo),
agitation (The bottle was then capped and shaken; Mazzeo, p. 912, col. 2, para. 2, ll. 5-7),
filtering the supernatant (the resultant slurry was filtered; Mazzeo, p. 912, col. 2, para. 2, ll. 8-10),
7) diluting the filtrate (The resulting filtrate was diluted; Mazzeo, p. 912, col. 2, para. 2, l. 11), and
8) measuring the anion content of the filtrate using ion chromatography (samples were analyzed for phosphate levels by ion chromatography; p. 912, col. 2, para. 3, ll. 1-2).
Bianchi fails to teach:
2) adding SIB buffer comprising 36 mM NaCI, 20 mM NaH2PO4, 50 mM 2-(N- morpholino)ethanesulfonic acid (MES) buffered to pH 5.5 to the amine polymer to achieve a final polymer concentration of 2.5 mg/ml,
3) incubating the mixture at 37 °C for 1 hour on a rotisserie mixer (Emphasis added),
4) pelleting the mixture,
5) removing 750 ml of supernatant,
Bianchi instead teaches adding a buffer comprising 20.0 mM KH2PO4, 100 mM BES, and 80 mM NaCl with the pH of the solution adjusted to 6.95–7.05 (Mazzeo, p. 912, col. 2, last para.). Bianchi also instead teaches the mixture was shaken with a Burrell wrist-action shaker instead of a rotisserie mixer (Mazzeo, p. 912, col. 2, para. 2, ll. 5-7).
Swearingen teaches a buffer solution with a pH of 5.5 (phosphate solutions were prepared so that a final pH of …5.5…after the addition of Renagel® capsules and tablets; p. 196, 2.3. Sample preparation, ll. 3-6).
Swearingen is considered to be analogous to the claimed invention because it is in the same field of endeavor for proton-binding polymers for oral administration. It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the buffer assay taught by Bianchi to incorporate the teachings of Swearinger by adjusting the pH of the buffer solution from 7 to 5.5 in order to test phosphate binding under acidic intestinal conditions. Reference Connor teaches that polyamine phosphate binders become increasingly protonated as pH decreases ([0048]), and this protonation directly increases anion binding affinity. Likewise, Swearinger teaches that “it has also been shown that there are more protonated amines at pH 5.5 than at pH 7.0” (p. 200, col. 2, ll. 11-13). Additionally, Applicant’s own reference, Fordtran, Fig. 7 shows that intestinal pH ranges between about 4 and 8. Therefore, such an adjustment would yield the predictable results of improving phosphate-binding performance under physiologically appropriate conditions to be used in testing for efficacy of the drug (See MPEP 2143(I)(C)).
Bianchi fails to teach:
2) adding SIB buffer comprising 36 mM NaCI, 20 mM NaH2PO4, 50 mM 2-(N- morpholino)ethanesulfonic acid (MES) buffered to pH 5.5 to the amine polymer to achieve a final polymer concentration of 2.5 mg/ml,
3) incubating the mixture at 37 °C for 1 hour on a rotisserie mixer (Emphasis added),
4) pelleting the mixture,
5) removing 750 ml of supernatant
Bianchi instead teaches adding a buffer comprising 20.0 mM KH2PO4, 100 mM BES, and 80 mM NaCl (Mazzeo, p. 912, col. 2, last para.). Bianchi also instead teaches the mixture was shaken with a Burrell wrist-action shaker instead of a rotisserie mixer (Mazzeo, p. 912, col. 2, para. 2, ll. 5-7).
Connor teaches
2) adding SIB buffer comprising 2-(N- morpholino)ethanesulfonic acid (MES) to the amine polymer (An aliquot of dried polymer…mixed…with a fixed volume, V(L), of the following buffer: buffer…100 mM MES sodium salt (morpholinoethanesulfonic acid); [0245]).
4) pelleting the mixture (“the solution was decanted by centrifugation and the supernatant
analyzed,” wherein the examiner understands the pellet to be defined as a fraction of sample remaining in the container after centrifugation due to the separation of sample by density due to centripetal force. Since a supernatant fluid was analyzed, the top layer (supernatant) has been removed and the pellet remains; [0245]).
Connor is considered to be analogous to the claimed invention because it is in the same field of endeavor for allylamine-based proton-binding polymers for oral administration. It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have substituted the BES taught by Bianchi with MES as taught by Connor ([00245]) since they are known equivalents as Good’s buffers that achieve the common purpose of assay stabilization (See MPEP 2143(I)(B)). Mazzeo explains that “100 mM BES, pKa 7.1, was chosen to hold the pH at 7.0,” (page 915, columns 1-2), and therefore use of MES with a pKa of 6.1 would be a more appropriate stabilizer at the pH of 5.5.
Modified Bianchi fails to teach:
2) adding SIB buffer comprising 36 mM NaCI, 20 mM NaH2PO4, 50 mM 2-(N- morpholino)ethanesulfonic acid (MES)(Emphasis added) to achieve a final polymer concentration of 2.5 mg/ml
3) incubating the mixture at 37 *C for 1 hour on a rotisserie mixer (Emphasis added),
5) removing 750 ml of supernatant,
Bianchi instead teaches adding a buffer comprising 20.0 mM KH2PO4, 100 mM BES, and 80 mM NaCl (Mazzeo, p. 912, col. 2, last para.). Bianchi also instead teaches the mixture was shaken with a Burrell wrist-action shaker instead of a rotisserie mixer (Mazzeo, p. 912, col. 2, para. 2, ll. 5-7).
Although Modified Bianchi is silent to teaching the specific concentrations of buffer ingredients to include 36 mM NaCI, 20 mM NaH2PO4, 50 mM 2-(N-morpholino)ethanesulfonic acid (MES), these concentrations are result-effective variables that can be optimized to mimic the intestinal conditions of the GI tract where the optimal binding occurs specifically at a pH of 5.5 (Connor, [0050][0247])(Swearinger, p. 200, col. 2, ll. 11-13), a well-understood technique to one of ordinary skill in the art (See MPEP 2144.05(II)). The components of the buffer are interdependent; so when pH is altered, corresponding adjustments in buffer composition (e.g. MES concentration), phosphate salt, and ionic strength must be made to maintain measurable equilibrium and ion chromatographic detectability. It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have optimized concentrations of these components and to have achieve this equilibrium balance required for further testing. As for the final polymer concentration of 2.5 mg/ml, Bianchi already creates a final volume by mixing a polymer with a buffer before testing and it would have obvious to one of ordinary skill in the art to choose a polymer concentration (such as 2.5 mg/ml) that would set the sample within a linear range of the calibration curve (See MPEP 2144.05(II))(Applicant has not supplied information for the criticality of such a final concentration). Additionally, KH2PO4 and NaH2PO4 are known equivalents for supplying phosphate ions and are therefore interchangeable for use in the assay (MPEP 2144.06(II)).
Modified Bianchi fails to teach:
3) incubating the mixture at 37 *C for 1 hour on a rotisserie mixer (Emphasis added),
5) removing 750 ml of supernatant,
Bianchi instead teaches that the mixture was shaken with a Burrell wrist-action shaker instead of a rotisserie mixer (Mazzeo, p. 912, col. 2, para. 2, ll. 5-7).
Cooper teaches incubating the mixture at 37 0C for 1 hour and removing supernatant (The solutions are well mixed and then placed into an orbital shaker at 37.degree. C. for 1 hour. The polymer is allowed to settle prior to removing a sample aliquot from each solution; [0258]).
Cooper is considered to be analogous to the claimed invention because it is in the same field of endeavor for proton-binding polymers for oral administration. It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have Modified Bianchi to incorporate the teachings of Cooper with the addition of steps 3 and 5 for incubating the mixture at 37 0C for 1 hour and removing supernatant in order to create a similar gastrointestinal environment and a more uniform and less concentrated sample, both routine sample preparation techniques. Incubating the mixture at 37 °C for 1 hour would help “to mimic the conditions of use of a phosphate binding polymer in a GI tract” (Connor, [0247]) by simulating the natural body temperature of 98.6 degrees Fahrenheit for testing while reducing the risk of contamination. “In a simulated gastrointestinal medium or a physiologically acceptable medium,” (Cooper, [0160]), the results of this test can be used in treating a live patient. Although Cooper does not specifically teach a removal of 750 mL, selecting a standardized volume after pelleting is a routine optimization that ensures sufficient sample volume for analysis while avoiding disturbance of the pellet. Choosing this amount is a predictable, result-effective adjustment that yields consistent assay reproducibility, and therefore represents an obvious modification (See MPEP 2144.05(II)).
Modified Bianchi fails to teach a rotisserie mixer.
Liu teaches a rotisserie mixer (Core-shell particle polymer samples were added to…glass…fecal extract was dispensed into the tube…all tubes were…rotating on a rotisserie mixer; [0348]).
Liu is considered to be analogous to the claimed invention because it is in the same field of endeavor for proton-binding polymers for use in the gastrointestinal tract. It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have substituted the orbital shaker taught by Bianchi in view of Swearinger, Connor, and Cooper (Cooper, [0258]) with the rotisserie mixer taught by Liu since it is well-known in the art that rotisserie mixers enhance mixing performance by maintaining solids in full suspension and preventing premature settling. Swapping the orbital shaker with the rotisserie mixer would yield the same predictable result of improved binding efficiency (See MPEP 2143(I)(B)).
Regarding claim 32, Modified Bianchi teaches the SIB assay of claim 31.
Modified Bianchi fails to teach wherein 10 mL of SIB buffer is added to the amine polymer. However, Modified Bianchi does teach “An aliquot of dried polymer of weight P(gr), was mixed under gentle agitation with a fixed volume, V(L), of the following buffer” (Connor, [0245])). This fixed volume can be in any range that would include 10mL. Additionally, initial volume of buffer added is a variable that can be optimized to achieve maximum binding capacity of the phosphate ion at equilibrium, a well-understood technique to one of ordinary skill in the art. This result-effective variable is routine in the art and would have been obvious to implement for optimization purposes (MPEP § 2144.05(II)).
Regarding claim 37, Modified Bianchi teaches the SIB assay of claim 31, wherein the supernatant is filtered using a syringe filter (The sample aliquot is filtered into a small vial using a disposable syringe and syringe filter; Cooper [0258]).
Claims 33-36 are rejected under 35 U.S.C. 103 as being unpatentable over Bianchi et al. (US 20100183732 A1) and Mazzeo (“A phosphate binding assay for sevelamer hydrochloride by
ion chromatography”; 1998; fully incorporated by reference) in view of Connor et. al. (US 20100029897 A1), Cooper et. al. (US 20100234309 A1), Swearingen et al. (“Determination of the binding parameter constants of Renagel® capsules and tablets utilizing the Langmuir approximation at various pH by ion chromatography”; 2002), and Liu et al. (US 20090186093 A1), as applied to claim 31 above, and in further view of Chen et. al. (US 20140072983 A1).
Regarding claim 33, Modified Bianchi teaches the SIB assay of claim 31, wherein the mixture is pelleted by centrifuging. Modified Bianchi fails to teach that the centrifuging is for 2 minutes at 1000Xg.
Chen teaches wherein the mixture is pelleted (centrifugation should leave relatively dry resin pellets in the wells; [0204]) by centrifuging at 1000 RPM (centrifuged at 1000-2000 RPM). Depending on the centrifuge chosen and the radius of the motor, this 1000 RPM can calculate to 1000Xg, and the duration of centrifugation can be optimized to yield the desired pelleting which may correspond to 2 minutes, a well-understood technique to one of ordinary skill in the art. This result-effective variable is routine in the art and would have been obvious to implement for optimization purposes (MPEP § 2144.05(II)).
Chen is considered to be analogous to the claimed invention because it is in the same field of endeavor for proton-binding polymer assays. It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have Modified Bianchi in view of Cooper to incorporate the teachings of Chen by centrifuging is for 2 minutes at 1000Xg. Routine optimization would have been obvious to implement to achieve the desired pelleting for maximum phosphate ion binding (MPEP 2144.05(II)).
Regarding claim 34, Modified Bianchi teaches the SIB assay of claim 31. Modified Bianchi fails to teach wherein the supernatant is filtered using a 96- well glass filter plate.
Chen teaches wherein the supernatant is filtered using a 96- well filter plate (wells of a multiscreen filter plate (e.g., Millipore catalog #MSHVS4510),” wherein MSHVS4510 corresponds to a sterile, clear 96-well filter plate that lessens non-specific binding and reduces variability in both background and signal intensities specifically for biochemical screening assays which will yield comparable results of an equivalent glass material filter plate; 0204].
Chen is considered to be analogous to the claimed invention because it is in the same field of endeavor for proton-binding polymers for oral administration. It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have Modified Bianchi in view of Cooper to incorporate the teachings of Chen by filtering the supernatant using a 96- well glass filter plate. Using the mechanism of a 96- well glass filter plate will help in optimizing for an increase in production for testing multiple samples at once (MPEP § 2144.05(II)). Instead of filtering samples one at a time, this preparation step will reduce the time required to achieve the comparable result of individual sample filtration. This is a common tool in the art to combat increased production times in the laboratory setting. It would have been obvious to make use of this known equipment for production scale-up purposes in the field of laboratory analysis.
Regarding claim 35, Modified Bianchi teaches the SIB assay of claim 34, wherein the 96-well glass filter plate has a collection plate fitted on the bottom (A fresh recipient 96-well plate was placed beneath the filter plate as a recipient plate; Chen, [0204]).
Regarding claim 36, Modified Bianchi teaches the SIB assay of claim 35, wherein the filter plate and the collection plate unit are centrifuged at 1000Xg (the recipient plate/filter plate combination was centrifuged at 1000-2000 RPM to collect the filtrate in the recipient plate; [204]). Depending on the centrifuge chosen and the radius of the motor, this 1000 RPM can calculate to 1000Xg, and the duration of centrifugation can be optimized to yield the desired pelleting which may correspond to 2 minutes, a well-understood technique to one of ordinary skill in the art. This result-effective variable is routine in the art and would have been obvious to implement for optimization purposes (MPEP § 2144.05(II)).
Chen is considered to be analogous to the claimed invention because it is in the same field of endeavor for proton-binding polymers for oral administration. It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have Modified Bianchi in view of Cooper to incorporate the teachings of Chen by centrifuging is for 2 minutes at 1000Xg. Additionally, centrifuging both filter and collection plate is a redundant step for sample purification in removing polymer or solids suspended in the solution in order to generate a lower signal-to-noise ratio. This well-known, routine optimization would have been obvious to implement to achieve the desired pelleting for maximum phosphate ion binding (MPEP § 2144.05(II)).
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
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Claims 31-37 are rejected on the ground of nonstatutory double patenting as being obvious over claim 1 of U.S. Patent No. US 11311571 B2 in view of Bianchi et al. (US 20100183732 A1) and Mazzeo (“A phosphate binding assay for sevelamer hydrochloride by ion chromatography”; 1998; fully incorporated by reference), Connor et. al. (US 20100029897 A1), and Cooper et. al. (US 20100234309 A1), and in further view of Chen et. al. (US 20140072983 A1)(claims 33-36).
Regarding claim 31, US 11311571 B2 teaches a Simulated Small Intestine Inorganic Buffer (SIB) assay (a Simulated Small Intestine Buffer (“SIB”) assay; claim 1) comprising the steps of:
1) providing a proton-binding, crosslinked amine polymer comprising the residues of (a) 2-Propen-1-ylamine or a salt thereof and (b) 1,3-Bis(allylamino)propane or a salt thereof (“the preformed crosslinked amine polymer is a copolymer comprising the residues of (a) 2-Propen-1-ylamine or a salt thereof and (b) 1,3-Bis(allylamino)propane or a salt thereof,” with “a phosphate ion binding capacity”; claim 1)
2) adding SIB buffer comprising 36 mM NaCI, 20 mM NaH2PO4, 50 mM 2-(N- morpholino)ethanesulfonic acid (MES) buffered to pH 5.5 to the amine polymer to achieve a final polymer concentration of 2.5 mg/ml (the SIB assay, the crosslinked amine polymer is combined with a SIB buffer consisting of 36 mM NaCl, 20 mM NaH.sub.2PO.sub.4 and 50 mM 2-(N-morpholino)ethanesulfonic acid (MES) buffered to pH 5.5 at a concentration of 2.5 mg/ml; claim 1),
3) incubating the mixture at 37 *C for 1 hour with agitation on a rotisserie mixer (the combination is incubated at 37° C. for 1 hour with agitation on a rotisserie mixer; claim 1).
US 11311571 B2 fails to teach:
4) pelleting the mixture,
5) removing 750 ml of supernatant,
6) filtering the supernatant,
7) diluting the filtrate, and
8) measuring the anion content of the filtrate using ion chromatography.
Connor teaches:
4) pelleting the mixture (“the solution was decanted by centrifugation and the supernatant
analyzed,” wherein the examiner understands the pellet to be defined as a fraction of sample remaining in the container after centrifugation due to the separation of sample by density due to centripetal force. Since a supernatant fluid was analyzed, the top layer (supernatant) has been removed and the pellet remains; [0245]).
Bianchi teaches:
filtering the supernatant (the resultant slurry was filtered; Mazzeo, p. 912, col. 2, para. 2, ll. 8-10),
7) diluting the filtrate (The resulting filtrate was diluted; Mazzeo, p. 912, col. 2, para. 2, l. 11), and
8) measuring the anion content of the filtrate using ion chromatography (samples were analyzed for phosphate levels by ion chromatography; p. 912, col. 2, para. 3, ll. 1-2).
Cooper teaches:
5) removing supernatant (The polymer is allowed to settle prior to removing a sample aliquot from each solution; [0258]). Although Cooper does not specifically teach a removal of 750 mL, selecting a standardized volume after pelleting is a routine optimization that ensures sufficient sample volume for analysis while avoiding disturbance of the pellet. Choosing this amount is a predictable, result-effective adjustment that yields consistent assay reproducibility, and therefore represents an obvious modification (See MPEP 2144.05(II)).
The above references are considered to be analogous to the claimed invention because it is in the same field of endeavor for proton-binding polymer assays. It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified US 11311571 B2 to incorporate the teachings of these references because each modification represents a predictable use of known assay techniques to improve mixing, maintain polymer suspension, simulate physiological intestinal conditions, and quantify phosphate binding through routine optimization. Combining these known elements yields the predictable result of each step functioning as it would separately (See MPEP 2143(I)(A)).
Regarding claim 32, Modified US 11311571 B2 teaches the SIB assay of claim 31, wherein 10 mL of SIB buffer is added to the amine polymer (10 mL of the buffer; claim 1).
Regarding claim 33, Modified US 11311571 B2 teaches the SIB assay of claim 31.
Modified US 11311571 B2 fails to teach the mixture is pelleted by centrifuging for 2 minutes at 1000Xg.
Chen teaches wherein the mixture is pelleted (centrifugation should leave relatively dry resin pellets in the wells; [0204]) by centrifuging at 1000 RPM (centrifuged at 1000-2000 RPM). Depending on the centrifuge chosen and the radius of the motor, this 1000 RPM can calculate to 1000Xg, and the duration of centrifugation can be optimized to yield the desired pelleting which may correspond to 2 minutes, a well-understood technique to one of ordinary skill in the art. This result-effective variable is routine in the art and would have been obvious to implement for optimization purposes (MPEP § 2144.05(II)).
Chen is considered to be analogous to the claimed invention because it is in the same field of endeavor for proton-binding polymer assays. It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have Modified Bianchi in view of Cooper to incorporate the teachings of Chen by centrifuging is for 2 minutes at 1000Xg. Routine optimization would have been obvious to implement to achieve the desired pelleting for maximum phosphate ion binding (MPEP 2144.05(II)).
Regarding claim 34, Modified US 11311571 B2 teaches the SIB assay of claim 31
Modified US 11311571 B2 fails to teach the supernatant is filtered using a 96-well glass filter plate.
Chen teaches wherein the supernatant is filtered using a 96- well filter plate (wells of a multiscreen filter plate (e.g., Millipore catalog #MSHVS4510),” wherein MSHVS4510 corresponds to a sterile, clear 96-well filter plate that lessens non-specific binding and reduces variability in both background and signal intensities specifically for biochemical screening assays which will yield comparable results of an equivalent glass material filter plate; 0204].
Chen is considered to be analogous to the claimed invention because it is in the same field of endeavor for proton-binding polymers for oral administration. It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have Modified Bianchi in view of Cooper to incorporate the teachings of Chen by filtering the supernatant using a 96- well glass filter plate. Using the mechanism of a 96- well glass filter plate will help in optimizing for an increase in production for testing multiple samples at once (MPEP § 2144.05(II)). Instead of filtering samples one at a time, this preparation step will reduce the time required to achieve the comparable result of individual sample filtration. This is a common tool in the art to combat increased production times in the laboratory setting. It would have been obvious to make use of this known equipment for production scale-up purposes in the field of laboratory analysis.
Regarding claim 35, Modified US 11311571 B2 teaches the SIB assay of claim 34, wherein the 96-well glass filter plate has a collection plate fitted on the bottom (A fresh recipient 96-well plate was placed beneath the filter plate as a recipient plate; Chen, [0204]).
Regarding claim 36, Modified US 11311571 B2 teaches the SIB assay of claim 35,
Modified fails to teach the filter plate and the collection plate unit are centrifuged at 1000Xg for 1 minute.
Chen teaches the filter plate and the collection plate unit are centrifuged at 1000Xg (the recipient plate/filter plate combination was centrifuged at 1000-2000 RPM to collect the filtrate in the recipient plate; [204]). Depending on the centrifuge chosen and the radius of the motor, this 1000 RPM can calculate to 1000Xg, and the duration of centrifugation can be optimized to yield the desired pelleting which may correspond to 2 minutes, a well-understood technique to one of ordinary skill in the art. This result-effective variable is routine in the art and would have been obvious to implement for optimization purposes (MPEP § 2144.05(II)).
Chen is considered to be analogous to the claimed invention because it is in the same field of endeavor for proton-binding polymers for oral administration. It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have Modified Bianchi in view of Cooper to incorporate the teachings of Chen by centrifuging is for 2 minutes at 1000Xg. Additionally, centrifuging both filter and collection plate is a redundant step for sample purification in removing polymer or solids suspended in the solution in order to generate a lower signal-to-noise ratio. This well-known, routine optimization would have been obvious to implement to achieve the desired pelleting for maximum phosphate ion binding (MPEP § 2144.05(II)).
Regarding claim 37, Modified US 11311571 B2 teaches the SIB assay of claim 31, wherein the supernatant is filtered using a syringe filter (The sample aliquot is filtered into a small vial using a disposable syringe and syringe filter; Cooper [0258]).
Conclusion
No claims are allowed.
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/V.S./Examiner, Art Unit 1758
/MARIS R KESSEL/Supervisory Patent Examiner, Art Unit 1758