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 .
DETAILED ACTION
Claims 1-20 are under consideration.
The instant application is a continuation (CON) of Application No. 16/980,435 filed September 14, 2020 (now abandoned), which is a 371 of PCT/CN2019/077749 filed March 12, 2019.
Election/Restrictions
Applicant’s election without traverse of the species “glucose,” “polyethylene caprolactam -polyvinyl acetate - polyethylene glycol graft copolymer,” and “kidney disease” reading on claims 1-20 in the reply filed on April 27, 2026 is acknowledged.
Claims 1-20 as filed on June 13, 2024 are pending and under consideration to the extent of the elected species, e.g., the species of osmotic agent is glucose, the species of toxin-removal agent is polyethylene caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer and the species of disease or condition is kidney disease.
Claim Objections
Claims 1, 5, 10, 12, 14 and 17-20 are objected to because of the following informalities:
Claims 1 and 14, 2nd wherein clause: “a biofluid” should recite “the biofluid”.
Claim 5: “and” should recite “or” to properly recite alternatives.
Claim 5 recites “AGE products”. Acronyms should be spelled out at the first recitation thereof.
Claims 10 and 19: “wherein” should presumably be inserted after the preamble.
Claim 12: “toxins” should recite “toxin” consistent with the antecedent.
Claim 12: “the” should be inserted before “biofluid”.
Claims 12 and 20: “than its initial amount” should presumably recite “from its initial amount” or some variation thereof because “at least” … “than” is grammatically awkward.
Claims 17-20: the preamble should recite “The method of claim” consistent with claims 15 and 16, or vice versa.
Appropriate correction is required.
Priority
Acknowledgment is made of applicant’s claim for foreign priority under 35 U.S.C. 119 (a)-(d). The certified copy has been filed in parent Application No. 16/980,435.
Claim Rejections - 35 USC § 112(a)
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 14-20 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for treatment, does not reasonably provide enablement for prevention. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to practice the invention commensurate in scope with these claims.
The Federal Circuit developed a framework of factors in In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988), referred to as the Wands factors to assess whether any necessary experimentation required by the specification is “reasonable” or is “undue.”
These factors include, but are not limited to:
(A) the breadth of the claims;
(B) the nature of the invention;
(C) the state of the prior art;
(D) the level of one of ordinary skill;
(E) the level of predictability in the art;
(F) the amount of direction provided by the inventor;
(G) the existence of working examples; and
(H) the quantity of experimentation needed to make or use the invention based on the content of the disclosure.
See MPEP 2164. Claims 14-20 broadly encompass prevention of any and all toxin-related diseases or conditions by applying an intraperitoneal dialysis solution. Claims 15 and 16 are limited to prevention of kidney diseases and Claim 18 is limited to specific toxins. Intraperitoneal dialysis is a standard medical protocol for treating impaired renal function (e.g., Perl et al. “Peritoneal dialysis: from bench to bedside and bedside to bench,” American Journal of Physiology – Renal Physiology 311:F99-F1004, 2016). Intraperitoneal dialysis facilitates water removal, convection and diffusion of uremic toxins (Perl, abstract), thereby mimicking natural kidney function. Intraperitoneal dialysis is not known in the art to prevent impaired renal function or kidney disease as instantly claimed. Intraperitoneal dialysis has also proved beneficial in other indications, such as removal of excess metabolites or overdosed drugs, upon appropriate modification (e.g., Forster et al., “Liposome-supported peritoneal dialysis for detoxification of drugs and endogenous metabolites,” Science Translational Medicine 6(258):258ra141, 2014). While intraperitoneal dialysis is known to remove various solutes or/and toxins from the body, intraperitoneal dialysis is not known in the art to prevent any disease or condition. The instant specification discloses several working examples drawn to removal of urea (e.g., paragraphs [0251], [0275], [0303], [0327]), removal of creatinine (e.g., paragraphs [0259], [0283], [0311], [0335]) and removal of indoxyl sulfate (e.g., paragraphs [0267], [0291], [0319], [0343]). The instant specification does not disclose practice of methods as instantly claimed prevent any disease or condition. Although the level of skill in the art is high and the state of the art is advanced, the specification does not provide guidance that would allow the skilled artisan to apply or administer a dialysis solution as instantly claimed in order to prevent toxin-related diseases or conditions as instantly claimed. Absent guidance, the amount of experimentation necessary to practice the full scope of the methods as instantly claimed is undue.
Claim Rejections - 35 USC § 112(b)
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 2, 3, 8-13, 18 and 20 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor, or for pre-AIA the applicant regards as the invention.
Claims 2, 3 and 7 independently recite the amount (weight/volume). It is unclear whether the parenthetical information is a positive claim limitation or whether the parenthetical information is merely exemplary.
Claims 8 and 18 independently recite AGE products (3-deoxyglucosone, …, pentosidine). It is unclear whether the parenthetical information is a positive claim limitation or whether the parenthetical information is merely exemplary. Claims 9-13 are included in this rejection because they depend from claim 8 and because they do not remedy the noted ambiguity.
Claims 12, 13 and 20 independently recite toxins (or non-free amount). It is unclear whether the parenthetical information is a positive claim limitation or whether the parenthetical information is merely exemplary.
Claim Rejections - 35 USC § 112(d)
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 3 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 3 recites the amount is not higher than 4%, …, or not higher than 0.25%, however, claim 2 from which claim 3 depends the amount is at least 0.0001%, …, or at least 0.25%. The ranges of claim 3 encompass 0%, omitting the ranges of claim 2. Additionally, the range of at least 0.25% of claim 3 omits / contradicts the range of not higher than 0.25% of claim 2.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
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 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 1-20 are rejected under 35 U.S.C. 103 as being unpatentable over Gauthier et al. (US 4,976,683, published December 11, 1990) in view of Nolph et al. (EP 89,135, published September 21, 1983); Tanida et al. “Evaluation of the micellization mechanism of an amphiphilic graft copolymer with enhanced solubility of ipriflavone,” Chemical and Pharmaceutical Bulletin 64:68-72, 2016; and Meyer et al. “Uremia,” New England Journal of Medicine 357(13):1316-1325, 2007.
Gauthier teaches a method for peritoneal dialysis of a patient in need of such treatment comprising inter alia instilling an initial volume of an aqueous peritoneal dialysis solution composition comprising an osmotic agent, wherein the osmotic agent is present at an osmolarity that is greater than the osmolarity of the body fluids, and wherein a flux of water and solute (toxin, method for reducing a toxin, method of treating a toxin-related disease or condition) enters the composition from the body fluids (title; abstract; claims, in particular 1; paragraph bridging columns 1 and 2). The patients have inadequate kidney function (kidney disease) (column 1, lines 12-16), as required by instant claim 15 and the elected embodiment. Dialysis removes impurities, toxins and other small molecules such as urea (uremic toxin, uremia), the principle nitrogenous metabolite produced by the body (paragraph bridging columns 1 and 2; column 3, lines 3-16), as required by instant claims 8-10, 16-19.
The osmolarity of the composition is about 300 to 500 mOsm/L (claims 3, 4), as required by instant claim 4.
The osmotic agent is selected from the group inclusive of sugars (claim 11), as required by instant claim 5. Exemplary agents include dextrose (glucose) in an amount of 5% (paragraph bridging columns 8 and 9; column 9, lines 12-22; column 12, lines 5-28), as required by instant claims 6, 7 and the elected embodiment.
Gauthier further teaches patients with chronic renal failure (column 1, lines 18-20).
Gauthier does not teach a toxin-removal agent that is polyethylene caprolactam – polyvinyl acetate – polyethylene glycol graft copolymer as required by claims 1, 14 and the elected embodiment thereof.
Gauthier does not teach at least 0.0001% toxin-removal agent as required by claim 2.
Gauthier does not teach at most 4% toxin-removal agent as required by claim 3.
Gauthier does not teach the toxin is reduced to at most 50%, …, or at most 5% of the amount before treatment as required by claim 11.
Gauthier does not teach the toxin is reduced at least 10%, …, or at least 95% of the amount before treatment as required by claims 12, 20.
Gauthier does not teach the residual toxin is at most 90%, …, or at most 5% of the amount before treatment as required by claim 13.
These deficiencies are made up for in the teachings of Nolph, Tanida and Meyer.
Nolph, summarized at column 4, lines 29-38 of Gauthier, teaches a peritoneal dialysis solution containing 5 to 100 g/L (0.5 to 10 % w/v) sorbents for metabolic breakdown products (toxins) such as creatinine (uremic toxin) to be removed (title; abstract; claims; page 1, lines 4-15; page 3, lines 30-34; Examples), as required by instant claims 2, 3. The solution further comprises a sufficient amount of physiological salt to be osmotically compatible and an osmotic agent such as dextrose (glucose); exemplary dialysis solutions contain either 1.5 or 4.25 wt% dextrose (abstract; claim 1; page 3, lines 7-16; page 5, lines 1-8). Nolph further exemplifies enhanced removal of creatinine; various amounts of charcoal sorbent were added to determine its effect on creatine clearance (Examples; also, page 5, lines 24-30).
Tanida teaches solubilization enhancement properties of an amphipathic graft copolymer, Soluplus® (polyethylene caprolactam – polyvinyl acetate – polyethylene glycol graft copolymer as evidenced by paragraph [0103] of the instant specification), on test compounds (abstract; page 68, paragraph bridging columns; Figure 1; page 69, “Solubility Study”). Micelle formation of Soluplus® improves solubility; the calculated cmc of Soluplus® is 0.82 mg/mL (0.082 % w/v) (abstract; paragraph bridging pages 69 and 70; Figures 2, 4; page 70, rhc, full paragraph), as required by instant claims 2, 3. Furthermore, the polymer has an inherent binding site that allows hydrogen bonding and/or van der Waals interactions with drug molecules (page 68, paragraph bridging columns).
Meyer teaches treatment of uremia, which once encompassed all signs and symptoms of advanced kidney failure, is dominated by dialysis (page 1316, 1st and 3rd paragraphs). Urea is quantitatively the most important uremic solute (page 1317, rhc, full paragraph; Table 1). Dialysis is adjusted to remove about two thirds of total-body urea during each treatment (page 1318, rhc, full paragraph; Figure 1), as required by instant claims 11-13, 20. Removal of solutes can be increased by various modifications of the standard dialysis treatment (page 1318, rhc, full paragraph).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the aqueous peritoneal dialysis solution composition of Gauthier to further comprise solubilization enhancers inclusive of Soluplus® (polyethylene caprolactam – polyvinyl acetate – polyethylene glycol graft copolymer as evidenced by paragraph [0103] of the instant specification) as taught by Tanida in order to enhance the solubilization of solutes such as impurities, toxins and other small molecules such as urea for removal from the body. There would be a reasonable expectation of success because Nolph and Meyer independently teach it is known in the art to add sorbents or/and to modify dialysis treatments to increase removal of solutes.
Regarding claims 2 and 3, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to include solubilization enhancers inclusive of Soluplus® in an amount in excess of 0.82 mg/mL (0.082 % w/v) as taught by Tanida because the presence of micelles improves solubility. There would be a reasonable expectation of success because Nolph teaches it is known in the art to add sorbents for enhanced metabolic breakdown product removal in amounts from 5 to 100 g/L (0.5 to 10 % w/v). Additionally or/and alternatively, it would have been prima facie obvious to optimize the amount of Soluplus® in order to optimize / maximize solute / toxin removal. It is prima facie obvious to optimize such result-effective variables within prior art conditions or through routine experimentation. See MPEP 2144.05.
Regarding claims 11-13 and 20, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to practice the method for peritoneal dialysis of a patient in need of such treatment of Gauthier in view of Nolph and Tanida inclusive of patients with chronic renal failure until about two thirds of total-body urea is removed as taught by Meyer because this is the standard treatment for uremia or kidney disease. Additionally or/and alternatively, it would have been prima facie obvious to optimize the method in order to optimize / maximize solute / toxin removal. See MPEP 2144.05.
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Ash (GB 2,097,696) teaches sorbent mixtures for uremic substances for use in hemodialysis; creatinine can be removed using silica (title; abstract; claims; page 1, lines 92-94).
Leroux et al. (US 2015/0216802) teaches liposome compositions for use in peritoneal dialysis of patients suffering from endogenous or exogenous toxicopathies; the drug-entrapping liposome sequesters toxins (title; abstract; claims; paragraph [0015]).
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ALISSA PROSSER whose telephone number is (571)272-5164. The examiner can normally be reached M - Th, 10 am - 6 pm.
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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/ALISSA PROSSER/
Examiner, Art Unit 1619
/BENNETT M CELSA/Primary Examiner, Art Unit 1600
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