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 .
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.
Response to Arguments
Applicant's arguments filed February 17, 2026 have been fully considered and are considered persuasive.
Specifically, on pages 6-8 of the Remarks section as indicated by the page number at the bottom of each page, Applicant argues against the previous 103 prior art rejection of independent Claim 1, in which secondary reference Sternby et al., (“Sternby”, WO 2014/177656 A1), was relied upon to disclose the limitation “the total concentration of citrate of at least 28 mM and less than 35 mM”. Applicant argues that “a skilled artisan would not be motivated to arrive at the present claims based on the teachings of this Sternby to limit the volume of anticoagulation fluid [needed] to achieve a certain level of anticoagulation”, allegedly. Applicant asserts that Sternby is “entirely unrelated to the technical problem addressed by the present claims, which concern the storage stability and visual appearance of an acidic citrate concentrate in an oxygen-permeable plastic container under accelerated aging conditions”. In response, the Examiner notes that the claimed invention is directed toward “a package” which holds “an acidic citrate concentrate” which is also concerned with the concentration of citrate in the package, (See Claim 1, present invention), and that the package is also directed toward application in the field of “extracorporeal treatment of blood with the acidic citrate containing concentrate” which is explicitly stated in paragraph [0001] of the instant Specification of the present application. The Examiner notes that Applicant appears to exclude other reasons for applying the disclosed level of citrate from Sternby, in which its invention is also directed toward extracorporeal blood treatment, (See Technical Field, Sternby). The Examiner also notes that the instant Specification of the present application explicitly states that “citrate has another advantage as it can act as an anticoagulant”, (See paragraph [0010], instant Specification). To further extend these observations, the Examiner notes that primary reference Forsback et al., (“Forsback”, US 2015/0313858), explicitly discloses in paragraph [0017] that citrate “is an anticoagulant” and in paragraph [0021] that “to achieve a more complete anticoagulation…alternatively the concentration of citrate in the dialysis composition is raised”. The Examiner finds unpersuasive Applicant’s assertion that only the storage stability and visual appearance of the citrate in the plastic container is relevant based on the above findings above. In response to applicant’s argument that there is no teaching, suggestion, or motivation to combine the references, the examiner recognizes that obviousness may be established by combining or modifying the teachings of the prior art to produce the claimed invention where there is some teaching, suggestion, or motivation to do so found either in the references themselves or in the knowledge generally available to one of ordinary skill in the art. See In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988), In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992), and KSR International Co. v. Teleflex, Inc., 550 U.S. 398, 82 USPQ2d 1385 (2007).
On page 7, Applicant also argues that “a person of ordinary skill would not be motivated to modify Forsback based on the teachings of Sternby with a reasonable expectation of success” because Sternby uses anticoagulation fluid to be used in an extracorporeal blood circuit and interact with calcium to inhibit coagulation while Forsback is directed to dialysis fluid administered on the dialysate side and is not designed to interact with calcium to inhibit coagulation. However, the Examiner notes that Sternby also discloses that its anticoagulation fluid may be directly used together with a dialysis fluid, (See page 13, fourth paragraph, Sternby). Both references teach using its citrate containing composition for anticoagulation and for applying to another solution for a final composition that has a pH at physiologically acceptable levels. Thus, the Examiner finds that the references are reasonably analogous and can be modified together based on their relevant teachings. In response to applicant's argument for nonanalogous art, it has been held that a prior art reference must either be in the field of the inventor’s endeavor or, if not, then be reasonably pertinent to the particular problem with which the inventor was concerned, in order to be relied upon as a basis for rejection of the claimed invention. See In re Oetiker, 977 F.2d 1443, 24 USPQ2d 1443 (Fed. Cir. 1992).
On page 8, Applicant argues that using the teachings of Sternby allegedly “teaches away” from the disclosure of Forsback because Sternby discloses “maintaining a physiological pH to ensure blood compatibility” at a pH between 6-8 while Forsback has a concentrate with a pH of 2-3. Applicant argues that Sternby would teach away from adding acidic formulations to the blood, at such levels of pH of 2-3, and would be dangerous. The Examiner notes that adding acidic fluids directly to the blood generally would be considered unsafe, and points to Forsback’s own teaching that the acidic concentrate dialysis composition is designed to be mixed with a bicarbonate-containing solution into a final dialysis solution that has the resultant pH of between 6.5 to 8, (See paragraphs [0094]-[0103], Forsback). Thus, contrary to Applicant’s argument, Forsback also would introduce a final solution at a physiologically acceptable level of 6.5 to 8, not 2 to 3, which would indeed be dangerous. The Examiner finds Applicant’s argument here unpersuasive because neither reference teaches introducing such an acidic composition directly to the patient, and that the goal of both disclosed solutions is to end up with physiologically acceptable solutions for introduction to the patient in extracorporeal treatment.
Thus, the prior art rejections on the claims still stand for the reasons stated above.
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.
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.
Claim(s) 1-14 is/are rejected under 35 U.S.C. 103 as being unpatentable over Forsback et al., (“Forsback”, US 2015/0313858), in further in view of “Nexcel pharmaceutical films M312, M312A, M312C”, 29 January 2012 (2012-01-29) (“Nexcel”), in further view of Mabuchi et al., (“Mabuchi”, US 2009/0272686), in further view of Sternby et al., (“Sternby”, WO 2014/177656 A1).
Regarding Claims 1-8, Forsback discloses a package comprising:
an acidic citrate containing concentrate comprising:
a total concentration of citrate, (Example 17 among multiple examples, See paragraph [0143], anticipates the claimed range at this value); and
glucose (see ¶ [0039] “The acid concentrate dialysis solution may also comprise components and electrolytes like … glucose”; and ¶ [0080] “the present acid concentrate dialysis composition may contain certain amount of glucose, for example in a concentration of 0-11 mM.”);
citric acid and citrate in a (mole) ratio between 75:25 to 85:15 (see ¶ [0035] “Another embodiment of the invention an acid concentrate dialysis composition as described herein, where the ratio of citric acid to citrate is more than 1:1. For example, the ratio of citric acid to citrate is between about 1:1 to about 10:1, preferably about 2:1 to 6:1, more preferably between about 3:1 to about 6:1.”; and ¶ [0063] “Another example is where the ratio of citric acid to citrate is between about 1:1 to about 10:1, for example about 1:1 to about 6:1. Examples of suitable ratios are 1:1, 1.5:1, 2:1, 2.5:1, 3:1, 3.5:1, 4:1, 4.5:1, 5:1, 5.5:1, 6:1, 7:1, 8:1, 9:1, and 10:1.”; emphasis added),
where the acidic citrate containing concentrate has a pH of between 2 and 3 (see ¶ [0068] “The pH of the acid concentrate dialysis composition shall be less than 3.0, to avoid the forming of calcium complex, and to obtain a more stable concentrate composition. The acid concentrate dialysis composition as described herein shall have a pH of less than 2.8, for example the pH of the concentrate composition is less than 2.6, such as less than 2.5. For example, the acid concentrate dialysis composition has a pH of between 0.5 and 2.8; preferably pH between 1.0 and 2.6; more preferably, pH between 1.5 and 2.5. For example the pH is more than pH 1.5, and less than pH 2.6; preferably pH is between 1.5 and 2.5; more preferably pH is between 2 and 2.4, for example between 2 and 2.2.”; emphasis added).
Forsback does not explicitly disclose the total concentration of citrate of at least 28 mM and less than 35 mM; a plastic material having an oxygen permeation rate more than 2 g/m2/24h at 25 °C/ 90 % RH; the acidic citrate containing concentrate sealed in the plastic material container; and wherein the acidic citrate containing concentrate in the plastic material container, after storage for 14 days at 55°C and 40% RH, is not more intensely colored than a standard reference solution Y7 according to a standard test for “Appearance of Solution” as set forth in the Hemodialysis Solution of European Pharmacopeia 8.4.
Nexcel discloses commercially available plastic bags M312, M312A, and M312C which are a plastic material having an oxygen permeation rate more than 2 g/m2/24h, (see ¶ [1] “They are designed for demanding applications such as saline... dialysis solution…”; Examiner notes that Nexcel M312A has an oxygen permeation rate of 3.5 g/m2/day, according to paragraph [0089] of the instant Specification, anticipating the claimed range at this value, thus it is inherent); the acidic citrate containing concentrate sealed in the plastic material container; and wherein the acidic citrate containing concentrate in the plastic material container, after storage for 14 days at 55°C and 40% RH, is not more intensely colored than a standard reference solution Y7 according to a standard test for “Appearance of Solution” as set forth in the Hemodialysis Solution of European Pharmacopeia 8.4, (see ¶ [1] “They are designed for demanding applications such as saline... dialysis solution…”; Examiner notes that Example 4 of the instant application states that Nexcel M312A, a disclosed bag in Nexcel, demonstrates that the concentrate in this container/bag after 14 days, 55oC, and 40% RH, is “not more intensely colored than the reference solution Y7. Thus, it is inherent).
It would have been obvious to one of ordinary skill in the art before the effective filling date to have modified the concentrate of modified Forsback by incorporating a plastic material having an oxygen permeation rate more than 2 g/m2/24h; the acidic citrate containing concentrate sealed in the plastic material container; and wherein the acidic citrate containing concentrate in the plastic material container, after storage for 14 days at 55°C and 40% RH, is not more intensely colored than a standard reference solution Y7 according to a standard test for “Appearance of Solution” as set forth in the Hemodialysis Solution of European Pharmacopeia 8.4 as disclosed by NEXCEL to yield the predictable results of storing the concentrate in a storage bag for the handling of dialysis solutions, said bag being multilayer, having minimal particulates, excellent clarity, and extreme toughness; is PVS and DEHP free, sterilizable at 121 °C, heat sealable, resistant to abuse, has extremely low extractables, meets the requirements of Class VI, and is registered with the FDA (see NEXCEL, § Key benefits). MPEP § 2143.I.B.
Modified Forsback does not disclose that the oxygen permeation rate is measured at the conditions of 25 °C/ 90 % RH.
Mabuchi discloses a plastic material with an oxygen permeation rate is measured at the conditions of 25 °C/ 90 % RH, (See paragraph [0209], Mabuchi).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the invention to have modified the package of modified Forsback by incorporating that the oxygen permeation rate is measured at the conditions of 25 °C/ 90 % RH as in Mabuchi for “increasing the water content” by having a higher water vapor content or RH, (See paragraph [0212], Mabuchi), in order to provide an “inner atmospheric of the packaging bag [that] is conditioned to inhibit oxidization”, (See paragraph [0212], Mabuchi).
Modified Forsback does not disclose the total concentration of citrate of at least 28 mM and less than 35 mM.
Sternby discloses a package with the total concentration of citrate of at least 28 mM and less than 35 mM, (See page 10, second paragraph; a citrate of 25 mM can be selected and an acid citrate of 5 mM can also be selected, resulting in a total concentration of 30 mM and a ratio falling within 75:25 and 85:15).
It would have been obvious to one of ordinary skill in the art before the effective filling date to have modified the concentrate of modified Forsback by incorporating the total concentration of citrate of at least 28 mM and less than 35 mM as in Sternby in order to “limit the volume of anticoagulation fluid need to achieve a certain level of anticoagulation” by selecting a certain concentration of citrate, (See page 7, paragraph 4, Sternby).
Additional Disclosures Included:
Claim 2: The package according to claim 1 wherein the oxygen permeation rate of the plastic material container is of more than 2.5 g/m2/24h at 25 *C/90% RH, (see ¶ [1] “They are designed for demanding applications such as saline... dialysis solution…”; Examiner notes that Nexcel M312A has an oxygen permeation rate of 3.5 g/m2/day, according to paragraph [0089] of the instant Specification, anticipating the claimed range at this value, thus it is inherent; and See paragraph [0209], Mabuchi).
Claim 3: The package according to claim 1, wherein the acidic citrate containing concentrate comprises the citric acid and the citrate in a (mole) ratio of 80:20 (see ¶ [0063], Forsback, “Another example is where the ratio of citric acid to citrate is between about 1:1 to about 10:1, for example about 1:1 to about 6:1. Examples of suitable ratios are 1:1, 1.5:1, 2:1, 2.5:1, 3:1, 3.5:1, 4:1, 4.5:1, 5:1, 5.5:1, 6:1, 7:1, 8:1, 9:1, and 10:1.”; emphasis added).
Claim 4: The package according to claim 1, wherein the acidic citrate containing concentrate has a pH between 2.2 and 2.4, (see ¶ [0068], Forsback, “The pH of the acid concentrate dialysis composition shall be less than 3.0, to avoid the forming of calcium complex, and to obtain a more stable concentrate composition. The acid concentrate dialysis composition as described herein shall have a pH of less than 2.8, for example the pH of the concentrate composition is less than 2.6, such as less than 2.5. For example, the acid concentrate dialysis composition has a pH of between 0.5 and 2.8; preferably pH between 1.0 and 2.6; more preferably, pH between 1.5 and 2.5. For example the pH is more than pH 1.5, and less than pH 2.6; preferably pH is between 1.5 and 2.5; more preferably pH is between 2 and 2.4, for example between 2 and 2.2.”; emphasis added. Forsback explicitly discloses a narrow range that anticipates the claimed range at 2.2).
Claim 5: The package according to claim 1, wherein the acidic citrate containing concentrate comprises calcium (Ca2+) in a concentration of 49-85.5 mM, (see page 5, Table: General composition for dilution 1:35 and 1:45, respectively (amounts in mM); Calcium (Ca2+); Composition I anticipates the claimed range at a value of 49 mM).
Claim 6: The package according to claim 1 wherein the acidic citrate containing concentrate when diluted to a ready to use dialysis fluid comprises potassium (K+) in a concentration of 0-180 mM (see page 5, Forsback, compositions I-VI in diluted solution: K+ = 3 in all compositions).
Claim 7: The package according to claim 1 wherein the plastic material container comprises polyolefins, (a commercially available plastic material container, Nexcel M321A) is the same as a preferred embodiment of the invention (see specification page 16, lines 1-3 “The acidic concentrate was included in a package comprising a multilayer film of polyolefins (Sealed Air Nexcel M312A) having an oxygen permeation rate of 3.5 g/m2/day.”, Nexcel).
Claim 8: The package according to claim 1, wherein the acidic citrate containing concentrate comprises 3.5-495 mM glucose (see ¶ [0080], Forsback, “the present acid concentrate dialysis composition may contain certain amount of glucose, for example in a concentration of 0-11 mM.”; see also pages 5-6, compositions I-VI in diluted solution: glucose = 1.4, 1.4, 1.5, 1.5, 1.6, 1.6, respectively).
Regarding Claims 9-14, Forsback discloses an acidic citrate containing concentrate for mixing with water and a bicarbonate solution into a ready to use dialysis fluid, where the acidic citrate containing concentrate comprising:
a total concentration of citrate, (Example 17, among other examples); and
glucose (see ¶ [0039] “The acid concentrate dialysis solution may also comprise components and electrolytes like… glucose”; and ¶ [0080] “the present acid concentrate dialysis composition may contain certain amount of glucose, for example in a concentration of 0-11 mM.”); and
where the acidic citrate containing concentrate has a pH of between 2 and 3, (see ¶ [0068] “The pH of the acid concentrate dialysis composition shall be less than 3.0, to avoid the forming of calcium complex, and to obtain a more stable concentrate composition. The acid concentrate dialysis composition as described herein shall have a pH of less than 2.8, for example the pH of the concentrate composition is less than 2.6, such as less than 2.5. For example, the acid concentrate dialysis composition has a pH of between 0.5 and 2.8; preferably pH between 1.0 and 2.6; more preferably, pH between 1.5 and 2.5. For example the pH is more than pH 1.5, and less than pH 2.6; preferably pH is between 1.5 and 2.5; more preferably pH is between 2 and 2.4, for example between 2 and 2.2.”),
citric acid and citrate in a (mole) ratio of between 75:25 to 85:15 (see ¶ [0035] “Another embodiment of the invention an acid concentrate dialysis composition as described herein, where the ratio of citric acid to citrate is more than 1:1. For example, the ratio of citric acid to citrate is between about 1:1 to about 10:1, preferably about 2:1 to 6:1, more preferably between about 3:1 to about 6:1.”; and ¶ [0063] “Another example is where the ratio of citric acid to citrate is between about 1:1 to about 10:1, for example about 1:1 to about 6:1. Examples of suitable ratios are 1:1, 1.5:1, 2:1, 2.5:1, 3:1, 3.5:1, 4:1, 4.5:1, 5:1, 5.5:1, 6:1, 7:1, 8:1, 9:1, and 10:1.”; emphasis added).
Forsback does not disclose the total concentration of citrate of at least 28 mM and less than 35 mM; a plastic material having an oxygen permeation rate more than 2 g/m2/24h at 25 °C/ 90 % RH; the acidic citrate containing concentrate sealed in the plastic material container; and wherein the acidic citrate containing concentrate in the container, after storage for 14 days at 55°C and 40% RH, is not more intensely colored than a standard reference solution Y7 according to a standard test for “Appearance of Solution” as set forth in the Hemodialysis Solution of European Pharmacopeia 8.4.
Nexcel discloses commercially available plastic bags M312, M312A, and M312C which are a plastic material having an oxygen permeation rate more than 2 g/m2/24h, (see ¶ [1] “They are designed for demanding applications such as saline... dialysis solution…”; Examiner notes that Nexcel M312A has an oxygen permeation rate of 3.5 g/m2/day, according to paragraph [0089] of the instant Specification, anticipating the claimed range at this value, thus it is inherent); the acidic citrate containing concentrate sealed in the plastic material container; and wherein the acidic citrate containing concentrate in the container, after storage for 14 days at 55°C and 40% RH, is not more intensely colored than a standard reference solution Y7 according to a standard test for “Appearance of Solution” as set forth in the Hemodialysis Solution of European Pharmacopeia 8.4, (see ¶ [1] “They are designed for demanding applications such as saline... dialysis solution…”; Examiner notes that Example 4 of the instant application states that Nexcel M312A, a disclosed bag in Nexcel, demonstrates that the concentrate in this container/bag after 14 days, 55oC, and 40% RH, is “not more intensely colored than the reference solution Y7. Thus, it is inherent).
It would have been obvious to one of ordinary skill in the art before the effective filling date to have modified the concentrate of Forsback by incorporating a plastic material having an oxygen permeation rate more than 2 g/m2/24h; the acidic citrate containing concentrate sealed in the plastic material container; and wherein the acidic citrate containing concentrate in the container, after storage for 14 days at 55°C and 40% RH, is not more intensely colored than the standard reference solution Y7 according to the standard test for “Appearance of Solution” as set forth in the Hemodialysis Solution of European Pharmacopeia 8.4 as dislcosed by NEXCEL to yield the predictable results of storing the concentrate in a storage bag for the handling of dialysis solutions, said bag being multilayer, having minimal particulates, excellent clarity, and extreme toughness; is PVS and DEHP free, sterilizable at 121 °C, heat sealable, resistant to abuse, has extremely low extractables, meets the requirements of Class VI, and is registered with the FDA (see NEXCEL, § Key benefits). MPEP § 2143.I.B.
Modified Forsback does not disclose that the oxygen permeation rate is measured at the conditions of 25 °C/ 90 % RH.
Mabuchi discloses a plastic material with an oxygen permeation rate is measured at the conditions of 25 °C/ 90 % RH, (See paragraph [0209], Mabuchi).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the invention to have modified the package of modified Forsback by incorporating that the oxygen permeation rate is measured at the conditions of 25 °C/ 90 % RH as in Mabuchi for “increasing the water content” by having a higher water vapor content or RH, (See paragraph [0212], Mabuchi), in order to provide an “inner atmospheric of the packaging bag [that] is conditioned to inhibit oxidization”, (See paragraph [0212], Mabuchi).
Modified Forsback does not disclose the total concentration of citrate of at least 28 mM and less than 35 mM.
Sternby discloses a package with the total concentration of citrate of at least 28 mM and less than 35 mM, (See page 10, second paragraph; a citrate of 25 mM can be selected and an acid citrate of 5 mM can also be selected, resulting in a total concentration of 30 mM and a ratio falling within 75:25 and 85:15).
It would have been obvious to one of ordinary skill in the art before the effective filling date to have modified the concentrate of modified Forsback by incorporating the total concentration of citrate of at least 28 mM and less than 35 mM as in Sternby in order to “limit the volume of anticoagulation fluid need to achieve a certain level of anticoagulation” by selecting a certain concentration of citrate, (See page 7, paragraph 4, Sternby).
Additional Disclosures Included:
Claim 10: The acidic citrate containing concentrate according to claim 9, wherein the oxygen permeation rate of the container is of more than 2.5 g/m2/24h at 25 *C/90% RH, (see ¶ [1], Forsback, “They are designed for demanding applications such as saline... dialysis solution…”; Examiner notes that Nexcel M312A has an oxygen permeation rate of 3.5 g/m2/day, according to paragraph [0089] of the instant Specification, anticipating the claimed range at this value, thus it is inherent; and See paragraph [0209], Mabuchi).
Claim 11: The acidic citate containing concentrate according to claim 9 wherein acidic citrate containing concentrate comprised the citric acid and the citrate in a (mole) ratio of 80:20 (see ¶ [0063], Forsback, “Another example is where the ratio of citric acid to citrate is between about 1:1 to about 10:1, for example about 1:1 to about 6:1. Examples of suitable ratios are 1:1, 1.5:1, 2:1, 2.5:1, 3:1, 3.5:1, 4:1, 4.5:1, 5:1, 5.5:1, 6:1, 7:1, 8:1, 9:1, and 10:1.”; emphasis added).
Claim 12: The acidic citate containing concentrate according to claim 9, wherein the acidic citrate containing concentrate has a pH between 2.2 and 2.4, (see ¶ [0068], Forsback, “The pH of the acid concentrate dialysis composition shall be less than 3.0, to avoid the forming of calcium complex, and to obtain a more stable concentrate composition. The acid concentrate dialysis composition as described herein shall have a pH of less than 2.8, for example the pH of the concentrate composition is less than 2.6, such as less than 2.5. For example, the acid concentrate dialysis composition has a pH of between 0.5 and 2.8; preferably pH between 1.0 and 2.6; more preferably, pH between 1.5 and 2.5. For example the pH is more than pH 1.5, and less than pH 2.6; preferably pH is between 1.5 and 2.5; more preferably pH is between 2 and 2.4, for example between 2 and 2.2.”; emphasis added. Forsback explicitly discloses a narrow range that anticipates the claimed range at 2.2).
Claim 13: The acidic citate containing concentrate according to claim 9, wherein the acidic citrate containing concentrate comprises calcium (Ca2+) in a concentration of 49-85.5 mM, (see page 5, Table: General composition for dilution 1:35 and 1:45, respectively (amounts in mM); Calcium (Ca2+); Composition I anticipates the claimed range at a value of 49 mM).
Claim 14: The acidic citate containing concentrate according to claim 9 wherein the acidic citrate containing concentrate when diluted to a ready to use dialysis fluid comprises potassium (K+) in a concentration of 0-180 mM (see page 5, Forsback, compositions I-VI in diluted solution: K+ = 3 in all compositions).
Claim(s) 15-19 is/are rejected under 35 U.S.C. 103 as being unpatentable over Forsback et al., (“Forsback”, US 2015/0313858), in view of Diederich, (US 4,500,309), in further view of “Nexcel pharmaceutical films M312, M312A, M312C”, 29 January 2012 (2012-01-29) (“Nexcel”), in further view of Mabuchi et al., (“Mabuchi”, US 2009/0272686), in further view of Sternby et al., (“Sternby”, WO 2014/177656 A1).
Regarding Claims 15-19, Forsback discloses a system for extracorporeal blood treatment in an extracorporeal blood circuit comprising:
an arterial blood line configured to be connected to a vascular access for withdrawing blood from a patient (see ¶ [0004] “the patient is connected by a blood line to the dialysis machine, which continuously withdraws blood from the patient.”);
the system comprising:
a filtration unit with a dialysate side and a blood side, where the blood side is in blood communication with the arterial and venous blood lines (see ¶ [0003] “Hemodialysis involves withdrawing blood from the body and cleaning it in an extracorporeal blood circuit, and then returning the cleansed blood to the body. The extracorporeal blood circuit includes a dialyzer, which comprises a semipermeable membrane. The semipermeable membrane has a blood side and a dialysate side, and waste substances and excess fluid are removed from the blood passing on the blood side of the semipermeable membrane through the semipermeable membrane over to the dialysate side of the semipermeable membrane.”);
a source of acidic citrate containing concentrate,
the acidic citrate containing concentrate comprising:
a total concentration of citrate, (Example 17 among other examples),
glucose (see ¶ [0039] “The acid concentrate dialysis solution may also comprise components and electrolytes like… glucose”; and ¶ [0080] “the present acid concentrate dialysis composition may contain certain amount of glucose, for example in a concentration of 0-11 mM.”); and
citric acid and citrate in a ratio (mole) of between 75:25 to 85:15 (see ¶ [0063] “Another example is where the ratio of citric acid to citrate is between about 1:1 to about 10:1, for example about 1:1 to about 6:1. Examples of suitable ratios are 1:1, 1.5:1, 2:1, 2.5:1, 3:1, 3.5:1, 4:1, 4.5:1, 5:1, 5.5:1, 6:1, 7:1, 8:1, 9:1, and 10:1.”; emphasis added),
a source of bicarbonate (see ¶ [0082] “to form an acid concentrate composition intended to be combined and mixed with a base, for example a basic solution comprising bicarbonate to form a final dialysis composition.”),
where the system is configured to mix the acidic citrate containing concentrate with the bicarbonate (see ¶ [0094] “The acid concentrate dialysis composition provided where the acid concentrate dialysis composition is to be diluted and mixed with a bicarbonate-containing solution into a dialysis solution”) provide a ready to use dialysis fluid comprising:
130-150 nM sodium (Na+) (see page 5, composition I in diluted solution Sodium (Na2+) = 103); and
20-40 mM bicarbonate (see ¶ [0095]-[0098] “The acid concentrate dialysis composition is intended to be mixed with a base solution into a final dialysis fluid which may contain… and 20-40 mM bicarbonate, preferably 25-35 mM bicarbonate, or more preferably 34 mM bicarbonate”),
where the dialysis fluid comprises a total concentration of citrate of at least 0.8 mM and less than 1.0 nM, Forsback teaches where the total concentration of citrate in the dialysis fluid is in the range of 1.0-6 mM (See Example 46, “citrate” 0.8 mM, paragraph [0172], anticipates the claimed range at this value),
the ready to use dialysis fluid has a pH above 7.25; (see ¶ [0094] The acid concentrate dialysis composition provided where the acid concentrate dialysis composition is to be diluted and mixed with a bicarbonate-containing solution into a dialysis solution… has a physiologically acceptable pH of between 6.5-8, more preferably pH of 6.8-7.5, for example pH of 7.0-7.4.”; anticipates the claimed range at values of 7.25 to 8, 7.25 to 7.5, 7.25 to 7.4).
Forsback does not disclose the total concentration of citrate of at least 28 mM and less than 35 mM; wherein a venous blood line configured to be connected to the vascular access for returning blood to the patient; the acidic citrate containing concentrate is sealed in a container having an oxygen permeation rate of more than 2 g/m2/24h at 25 0C/ 90 % RH; and wherein the acidic citrate containing concentrate in the container, after storage for 14 days at 55°C and 40% RH, is not more intensely colored than a standard reference solution Y7 according to a standard test for “Appearance of Solution” as set forth in the Hemodialysis Solution of European Pharmacopeia 8.4.
Diederich discloses a venous blood line configured to be connected to the vascular access for returning blood to the patient, wherein an extracorporeal blood circuit comprising a venous blood line configured to be connected to the vascular access for returning blood to the patient (see column 4, line(s) 4-15 “Turning first to the drawing, treatment apparatus 10 is illustrated in the FIGURE for hemodialysis with or without hemoperfusion of a patient’s blood, withdrawn from a limb such as arm 12. The overall apparatus 10 includes an arterial needle 14 operatively coupled to an arterial blood line 16, the latter being ultimately coupled to a standard capillary dialyzer 18. A return or venous blood line 20 is connected to the output end of dialyzer 18, and to a venous needle 22. It will be observed that the needles 14 and 22 are respectively inserted into the patient’s arm 12 at appropriate locations for withdrawal and return of blood.”) in order to return the treated blood to the patient while performing continuous hemodialysis.
It would have been obvious to a person having ordinary skill in the art before the effective filling date to have modified the system of Forsback by incorporating wherein a venous blood line configured to be connected to the vascular access for returning blood to the patient as in Diederich to yield the predictable results of returning the treated blood to the patient while performing continuous hemodialysis. MPEP 2143.A.
Modified Forsback does not disclose the acidic citrate containing concentrate is sealed in a container having an oxygen permeation rate of more than 2 g/m2/24h at 25 0C/ 90 % RH; and wherein the acidic citrate containing concentrate in the container, after storage for 14 days at 55°C and 40% RH, is not more intensely colored than the standard reference solution Y7 according to the standard test for “Appearance of Solution” as set forth in the Hemodialysis Solution of European Pharmacopeia 8.4.
Nexcel discloses commercially available plastic bags M312, M312A, and M312C which are a plastic material having an oxygen permeation rate more than 2 g/m2/24h, (see ¶ [1] “They are designed for demanding applications such as saline... dialysis solution…”; Examiner notes that Nexcel M312A has an oxygen permeation rate of 3.5 g/m2/day, according to paragraph [0089] of the instant Specification, anticipating the claimed range at this value, thus it is inherent); the acidic citrate containing concentrate sealed in the plastic material container; and wherein the acidic citrate containing concentrate in the container, after storage for 14 days at 55°C and 40% RH, is not more intensely colored than the standard reference solution Y7 according to the standard test for “Appearance of Solution” as set forth in the Hemodialysis Solution of European Pharmacopeia 8.4, (see ¶ [1] “They are designed for demanding applications such as saline... dialysis solution…”; Examiner notes that Example 4 of the instant application states that Nexcel M312A, a disclosed bag in Nexcel, demonstrates that the concentrate in this container/bag after 14 days, 55oC, and 40% RH, is “not more intensely colored than the reference solution Y7. Thus, it is inherent).
It would have been obvious to one of ordinary skill in the art before the effective filling date to have modified the system of modified Forsback by incorporating a plastic material having an oxygen permeation rate more than 2 g/m2/24h; the acidic citrate containing concentrate sealed in the plastic material container; and wherein the acidic citrate containing concentrate in the container, after storage for 14 days at 55°C and 40% RH, is not more intensely colored than the standard reference solution Y7 according to the standard test for “Appearance of Solution” as set forth in the Hemodialysis Solution of European Pharmacopeia 8.4 as disclosed by NEXCEL to yield the predictable results of storing the concentrate in a storage bag for the handling of dialysis solutions, said bag being multilayer, having minimal particulates, excellent clarity, and extreme toughness; is PVS and DEHP free, sterilizable at 121 °C, heat sealable, resistant to abuse, has extremely low extractables, meets the requirements of Class VI, and is registered with the FDA (see NEXCEL, § Key benefits). MPEP § 2143.I.B.
Modified Forsback does not disclose that the oxygen permeation rate is measured at the conditions of 25 °C/ 90 % RH.
Mabuchi discloses a plastic material with an oxygen permeation rate is measured at the conditions of 25 °C/ 90 % RH, (See paragraph [0209], Mabuchi).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the invention to have modified the system of modified Forsback by incorporating that the oxygen permeation rate is measured at the conditions of 25 °C/ 90 % RH as in Mabuchi for “increasing the water content” by having a higher water vapor content or RH, (See paragraph [0212], Mabuchi), in order to provide an “inner atmospheric of the packaging bag [that] is conditioned to inhibit oxidization”, (See paragraph [0212], Mabuchi).
Modified Forsback does not disclose the total concentration of citrate of at least 28 mM and less than 35 mM.
Sternby discloses a package with the total concentration of citrate of at least 28 mM and less than 35 mM, (See page 10, second paragraph; a citrate of 25 mM can be selected and an acid citrate of 5 mM can also be selected, resulting in a total concentration of 30 mM and a ratio falling within 75:25 and 85:15).
It would have been obvious to one of ordinary skill in the art before the effective filling date to have modified the concentrate of modified Forsback by incorporating the total concentration of citrate of at least 28 mM and less than 35 mM as in Sternby in order to “limit the volume of anticoagulation fluid need to achieve a certain level of anticoagulation” by selecting a certain concentration of citrate, (See page 7, paragraph 4, Sternby).
Additional Disclosures Included:
Claim 16: The system according to claim 15 wherein the ready to use dialysis fluid has a pH above 7.3, (see ¶ [0094] The acid concentrate dialysis composition provided where the acid concentrate dialysis composition is to be diluted and mixed with a bicarbonate-containing solution into a dialysis solution… has a physiologically acceptable pH of between 6.5-8, more preferably pH of 6.8-7.5, for example pH of 7.0-7.4.”; Forsback anticipates the claimed range in multiple disclosed ranges, such as 7.3 to 8, 7.3 to 7.5, or 7.3 to 7.4).
Claim 17: The system according to claim 15, wherein acidic citrate containing concentrate comprised the citric acid and citrate in a (mole) ratio of 80:20, (see ¶ [0063], Forsback, “Another example is where the ratio of citric acid to citrate is between about 1:1 to about 10:1, for example about 1:1 to about 6:1. Examples of suitable ratios are 1:1, 1.5:1, 2:1, 2.5:1, 3:1, 3.5:1, 4:1, 4.5:1, 5:1, 5.5:1, 6:1, 7:1, 8:1, 9:1, and 10:1.”; emphasis added).
Claim 18: The system according to claim 15 wherein the ready to use dialysis fluid comprises calcium (Ca2+) in a concentration of 1.4 to 1.9 mM, (see page 5, Forsback, compositions I-VI in diluted solution: Ca2+ = 1.4, 1.4, 1.5, 1.5, 1.6, 1.6, respectively).
Claim 19: The system according to claim 15, wherein the oxygen permeation rate of the container comprising the acidic citrate containing concentrate is more than 2.5 g/m2/24h at 25*C/90 % RH, (see ¶ [1] “They are designed for demanding eapplications such as saline... dialysis solution…”; Examiner notes that Nexcel M312A has an oxygen permeation rate of 3.5 g/m2/day, according to paragraph [0089] of the instant Specification, anticipating the claimed range at this value, thus it is inherent; and See paragraph [0209], Mabuchi).
Conclusion
THIS ACTION IS MADE FINAL. 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.
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/JONATHAN M PEO/Primary Examiner, Art Unit 1779
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