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 .
Priority
The present application, filed November 13, 2023, is a national stage application of PCT/CN2021/093850, filed May 14, 2021.
Status of the Application
Claims 1-9 are pending and examined on the merits herein.
Drawings
The drawings are objected to because Figures 5, 7, and 8 are sufficiently low resolution that information contained therein cannot be interpreted. Please replace Figures 5, 7, and 8 with higher resolution images.
Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Claim Interpretation
Claim 8 recites: “An alginate oligosaccharide or a pharmaceutically acceptable salt thereof for treatment of acute kidney injury, wherein the alginate oligosaccharide is an alginate disaccharide, an alginate trisaccharide, or an alginate tetrasaccharide.
The limitation “for treatment of acute kidney injury” is interpreted herein as an intended use of the alginate oligosaccharide of claim 8.
MPEP 2111.02 (II) states: “During examination, statements in the preamble reciting
the purpose or intended use of the claimed invention must be evaluated to determine whether or not the recited purpose or intended use results in a structural difference (or, in the case of process claims, manipulative difference) between the claimed invention and the prior art. If so, the recitation serves to limit the claim. …To satisfy an intended use limitation which is limiting, a prior art structure which is capable of performing the intended use as recited in the preamble meets the claim.”
In this instance, because the intended use does not limit the structure of the alginate oligosaccharide recited in the claim, claim 8 is satisfied by an alginate oligosaccharide
that satisfies the requirements of claim 8, even if that alginate oligosaccharide is not used for treatment of acute kidney injury.
Claim Objections
Claim 1 is amended to remove “Use of” and add “A method of treating an acute kidney injury with”. However, the claims do not include an indication that the claim is currently amended.
In addition, claim 1 is objected to because of the following informalities:
Claim 1 recites “an alginate tetrasccharide.” The examiner believes this to be a typographical error and should read as “an alginate tetrasaccharide.”
Appropriate correction is required.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claim 8 is rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception without significantly more. Claim 8 is drawn to an alginate oligosaccharide or a pharmaceutically acceptable salt thereof for treatment of acute kidney injury, wherein the alginate oligosaccharide is an alginate disaccharide, an alginate trisaccharide, or an alginate tetrasaccharide. As described in the above claim interpretation section, the limitation “for treatment of acute kidney injury” is an intended use of the alginate oligosaccharide of claim 8 and does not limit the structure of the product recited in the claim.
This claim does not include additional elements that are sufficient to amount to significantly more than the judicial exception.
Subject matter that is not patent eligible is determined by evaluating a claim for patentability based on the eligibility test set forth below:
(1) Is the claim directed to one of the four statutory categories, i.e., a process, machine, manufacture, or composition of matter? For the instant claim, the answer is “Yes” because the claim is directed to a composition of matter.
(2a) Prong 1: Does the claim recite or involve a judicial exception? The answer is “Yes” because the claim is drawn to an alginate oligosaccharide or salt thereof, wherein the alginate oligosaccharide is an alginate disaccharide, an alginate trisaccharide, or an alginate tetrasaccharide.
As evidence, Wang (Wang, Y.; et al. Marine Drugs 2019, vol. 17, 308; cited in PTO-892) teaches that alginate is an acidic hetero-polysaccharide extracted from brown algae that contains two different uronic acids, including α-l-guluronic acid (G) and β-d-mannuronic acid (M) arranged into three different kinds of blocks by (1→4)-linked monosaccharides: homopolymeric G blocks, polyguluronate (PolyG); homopolymeric M blocks, polymannuronate (PolyM); and random or heteropolymeric blocks of alternating M and G units (PolyMG) (p. 1, Introduction section, first paragraph). Therefore, alginate is a product of nature, because it is isolated from brown algae.
Wang further teaches a polysaccharide lyase family 7 (PL7) alginate lyase-encoding gene, aly08, was cloned from the marine bacterium Vibrio sp. SY01 and expressed in Escherichia coli. Wang teaches the purified alginate lyase Aly08, degraded alginates into disaccharides and trisaccharides in an endo-manner (p. 1, Abstract, lines 3-10). Thus the products produced Aly08 are alginate disaccharides and trisaccharides.
Therefore, the alginate disaccharides, trisaccharides, and tetrasaccharides recited in claim 8 are products of nature, because alginate is produced by brown algae in nature and degraded into alginate disaccharides and trisaccharides by the protein encoded by the aly08 gene in the marine bacterium Vibrio sp. SY01. Therefore, absent evidence that Aly08 does not degrade alginate in to disaccharides, trisaccharides, and tetrasaccharides under any conditions in the marine bacterium Vibrio sp. SY01, the alginate oligosaccharide of claim 8 is a product of nature.
(2a) Prong 2: Does the claim recite additional elements that integrate the judicial exception into a practical application? The answer is “No” because the claim recites that the oligosaccharide is “for treating acute kidney injury,” but this is interpreted as an intended use of the alginate oligosaccharide and does not limit the structure of the product recited in the claim.
(2b) Does the claim as a whole recite additional elements that amount to something significantly more than the judicial exception(s)? The answer is “No.”
The claim is drawn to an alginate oligosaccharide or salt thereof, wherein the alginate oligosaccharide is an alginate disaccharide, an alginate trisaccharide, or an alginate tetrasaccharide. The closest counterpart to the claimed mixture is the oligosaccharide product resulting from alginate digestion by Aly08 in marine bacterium Vibrio sp. SY01.
However, there is nothing to suggest that the alginate disaccharides, trisaccharides, and tetrasaccharides recited in claim 8 have any particular change in structure or function or any other characteristic resulting in something markedly different from this product as it occurs in nature.
In view of the foregoing, there is no indication that the alginate oligosaccharide or salt thereof recited in claim 8, wherein the alginate oligosaccharide is an alginate disaccharide, an alginate trisaccharide, or an alginate tetrasaccharide, has a markedly different structure, function, or property that would confer eligibility on these naturally occurring oligosaccharides.
Claim Rejections - 35 USC § 112
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 1-7 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 applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claims 1 recites: A method of treating an acute kidney injury with an alginate
oligosaccharide or a pharmaceutically acceptable salt thereof in preparation of a drug for
treatment of acute kidney injury, wherein the alginate oligosaccharide is an alginate disaccharide,
an alginate trisaccharide, or an alginate tetrasaccharide.
In this instance, claim 1 does not recite a step of administering an alginate oligosaccharide or a pharmaceutically acceptable salt thereof or any other method step, and thus it is unclear how an acute kidney injury would one would practice the method of be treated using this method.
Claim 1 appears to claim the method of treating an acute kidney injury with an alginate oligosaccharide by preparing a drug for treatment of acute kidney injury. If this is the intended meaning of claim 1, because claim 1 does not recite a step of administering an alginate oligosaccharide or a step of preparing a drug for treating acute kidney injury, it is again unclear how an acute kidney injury would be treated by practicing the method of claim 1.
Because claims 2-7 depend from claim 1 and fail to cure the above deficiency, claims 2-7 are also indefinite.
Claim Rejections - 35 USC § 102
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 (i.e., changing from AIA to pre-AIA ) 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.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim 8 is rejected under 35 U.S.C. 102(a)(1) as being anticipated by Agulhon (Agulhon, P.; et al. Biomacromolecules 2012, vol. 13, pp. 1899-1907; cited in PTO-892).
Agulhon teaches alginate is a polysaccharide of (1→4) linked α-L-guluronate (G) and β-D-mannuronate (M) (p. 1899, Introduction, lines 1-2). Agulhon teaches computational studies of the GG and MM disaccharides of alginate with and without being bound to metal ions (p. 1900, Figure 1 and Figure 1 caption; p. 1901, Figure 2). These disaccharides satisfy the limitations of claim 8.
As described in the above claim interpretation section, the limitation “for treating acute kidney injury” is interpreted as an intended use of the alginate oligosaccharide and does not limit the structure of the product recited in the claim.
Thus Agulhon anticipates claim 8.
Claim 8 is rejected under 35 U.S.C. 102(a)(1) and 35 U.S.C. 102(a)(2) as being anticipated by Murota (Publication no. US 2012/0058967 Al; cited in IDS received May 1, 2025).
Murota teaches that sodium alginate (10.0 kg) was dissolved in 90 liters of desalted water, a crude alginate lyase solution was added thereto, and the reaction was allowed to proceed at 40° C for 6 hours while the mixture was agitated. After the reaction solution was deproteinized and desalted, the resultant was lyophilized to obtain 4.2 kg of sodium alginate oligosaccharide powder (p. 5, Example 1, [0079], lines 1-7).
Murota teaches the constitutive sugars were α- or β-1,4-bound to each other, and D represents 4,5-unsaturated uronic acid (p. 6, [0084]). Murota teaches D-mannuronic acid (M) represented is by formula 2 and L-guluronic acid (G) is represented by formula 3 (p. 2, [0012]). The sugar represented by D, as shown in formula (I) (p. 2, [0012]), has the requirements of the monosaccharide Δ recited in the present claims.
Murota teaches the sodium alginate oligosaccharide (from Preparation Example 1 above) was subjected to high-performance liquid chromatography fractionation (p. 5, [0081], lines 1-3). Murota teaches additional fractionation of fractions with absorbance at 230 nm and NMR analysis of the components of these fractions showed the structures in [0085]-[0094], including, for example, D-G, D-M, D-G-G, D-M-G, and D-M-M (pp. 5-6, [0082]-[0094]).
Therefore, the products disclosed by Murota from treatment of sodium alginate with an alginate lyase are alginate disaccharides, trisaccharides, and tetrasaccharides, as required by claim 8.
Thus Murota anticipates claim 8.
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 1-6 and 9 are rejected under 35 U.S.C. 103 as being unpatentable over Murota (Publication no. US 2012/0058967 Al; cited in IDS received May 1, 2025) in view of Engoren (Engoren, M; et al. Critical Care Medicine 2014, vol. 42, pp. 2069-2074; cited in PTO-892), as evidenced by Agulhon (Agulhon, P.; et al. Biomacromolecules 2012, vol. 13, pp. 1899-1907; cited in PTO-892).
As described in the above rejection under 35 U.S.C. § 112(b), the invention encompassed by claims 1-6 is unclear. For the purposes of this rejection, these claims are interpreted as a method for treating acute kidney injury by administering a drug comprising alginate oligosaccharide for treatment of acute kidney injury, wherein the alginate oligosaccharide is an alginate disaccharide, an alginate trisaccharide, or an alginate tetrasaccharide. Alternatively, if claims 1-6 are intended to be drawn to a method for preparing a drug for treating acute kidney injury, then the alginate oligosaccharide composition of Murota described below would also reasonably satisfy the requirements of said drug.
Murota teaches as described in the above rejection under 35 U.S.C. § 102. In addition, Murota teaches and claims a method for inhibiting deterioration of renal functions by protecting a vascular, which comprises administering alginate oligosaccharide and/or a salt thereof to a patient (p. 9, claim 6). Murota teaches their alginate oligosaccharide as the product of alginate treated alginate lyase (p. 5, [0079], lines 1-7). This alginate oligosaccharide includes the disaccharides, trisaccharides, and tetrasaccharides recited in [0085]-[0094].
Moreover, Murota teaches embodiments evaluating the influence of alginate oligosaccharide on creatinine clearance and urinary protein (p. 8, [0120] and [0121]) in a rat model of salt-sensitive rats (p. 7, see Example 3, [0113] for a description of the experiment). Murota teaches that because severe high blood pressure induced by high-salt stress applied stress to the kidney, the creatinine clearance of the control group (administered a high salt feed) was significantly lower than that of the low-salt-stress group. Murota teaches the groups to which alginate oligosaccharide had been administered exhibited improvement compared with the control group in a dose-dependent manner. (p. 8, [0120], lines 1-9; see document p. 10, Figure 9 for data on the improved creatinine clearance). Murota teaches that this suggests the possibility that blood vessels may have been protected from stress caused by severe high blood pressure in the kidney comprising many capillary blood vessels, and a reduction in renal functions may have been consequently suppressed (p. 8, [0120], lines 9-13) (emphasis added).
In addition, Murota teaches that because severe high blood pressure induced by high-salt stress applied stress to the kidney, elevation in urinary protein levels was observed in the control
group, and the resulting value was significantly higher than that for the low-salt-stress group. Murota teaches the groups to which alginate oligosaccharide had been administered exhibited a significantly lower urinary protein level than the control group, which suggests the possibility that blood vessels may have been protected from stress caused by severe high blood pressure in the kidney, and a reduction in renal functions may have been consequently suppressed (p. 8, [0121], lines 1-13) (emphasis added).
Therefore, in view of Murota, one of ordinary skill in the art would have recognized that the alginate oligosaccharide composition disclosed by Murota may be administered to a subject for the purpose of inhibiting deterioration of renal functions, including improving the creatinine clearance and reducing urinary protein levels.
Murota does not teach a method for treating acute kidney injury, as required by claims 1-6 and 9.
Engoren teaches the effect of acute kidney injury and discharge creatinine level on mortality following cardiac surgery (p. 2069, Title). Engoren teaches that acute kidney injury after cardiac surgery is associated with increased operative and late mortality, and the objective of their study was to determine if short and long term mortality are systematically improved with completeness of postoperative acute kidney injury reversal or with amount of residual renal function (p. 2069, Abstract, Objectives section, lines 1-5).
Engoren teaches operative mortality in their study was 3.1% overall and was progressively worse with increasing acute kidney injury (p. 2069, Abstract, Measurements and Main Results section, lines 1-3). Engoren teaches that similar to the operative outcomes, late outcomes were progressively worse with rising amounts of acute kidney injury, the risk of late death was related to amount of acute kidney injury and remaining renal function at discharge (p. 2069, Abstract, Measurements and Main Results section, lines 5-8).
Engoren specifically relates creatinine levels to acute kidney injury severity and risk of late death. Engoren teaches that higher levels of acute kidney injury (e.g., KDIGO stages 1-3) showed greater changes in creatinine levels (p. 2070, Table 1) and higher percent mortality (p. 2070, Table 2). Engoren teaches level of acute kidney injury is independently associated with mortality (p. 2071, Table 3), and the expected survival of patients is lower with increasing creatinine levels at discharge (p. 2073, Figure 1).
Engoren concludes by stating that even minimal rises in serum creatinine are associated with increased operative and late death with the association increasing in proportion to the severity of the rise in creatinine, and that lesser residual renal function is also associated with higher risk of late mortality (p. 2074, left column, third full paragraph, lines 1-5).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the present application to administer the alginate oligosaccharide taught by Murota for the purposes of treating acute kidney injury. One of ordinary skill in the art would have been motivated to administer the alginate oligosaccharide taught by Murota for the purposes of treating acute kidney injury because Murota teaches their alginate oligosaccharide product for inhibiting deterioration of renal function, including improving creatinine clearance and reducing urinary protein levels, and because Engoren teaches that reduced renal function and increased creatinine levels are associated with increased death following cardiac surgery. Accordingly, one of ordinary skill in the art would have contemplated practicing the method for inhibiting deterioration of renal function by administering their alginate oligosaccharide to a patient following cardiac surgery and with acute kidney injury, because such a method is expected to inhibit deterioration of renal function and reduce creatinine levels by improving creatinine clearance, each of which would be expected to reduce the risk of death following cardiac surgery.
Regarding the specific alginate disaccharides, trisaccharides, and tetrasaccharides required by claims 2-5 and the salt of claim 6, Murota teaches their alginate oligosaccharide as including, for example, D-G, D-M, D-G-G, D-M-G, D-M-M, and D-G-G-G (p. 6, [0085]-[0094]), which satisfy the products required by claims 2-5. In addition, Murota teaches salts of their alginate oligosaccharides, including metal salts of alginate oligosaccharide, such as sodium alginate oligosaccharide, potassium alginate oligosaccharide, calcium alginate oligosaccharide, and mixtures thereof (p. 2, [0030], lines 1-4). As stated above, Murota teaches the sugar represented by D, as shown in formula (I) (p. 2, [0012]), which has the requirements of the monosaccharide Δ recited in the present claims.
Regarding the specific 1,4-linkages of the alginate oligosaccharides, as evidence, Agulhon teaches alginate is a polysaccharide of (1→4) linked α-L-guluronate (G) and β-D-mannuronate (M) (p. 1899, Introduction, lines 1-2). Therefore, the alginate oligosaccharides generated by treatment with alginate lyase possess the required (1→4) linkages, and the alginate disaccharides, trisaccharides, and tetrasaccharides of Murota thus would satisfy the limitations of the alginate oligosaccharides of claims 1-6 and 9.
Therefore the invention taken as a whole is prima facie obvious.
Claims 1-7 and 9 are rejected under 35 U.S.C. 103 as being unpatentable over Murota (Publication no. US 2012/0058967 Al; cited in IDS received May 1, 2025) in view of Wong (Wong, F.; et al. American Journal of Gastroenterology 2017, vol. 112, pp. 1103-1110; cited in PTO-892), as evidenced by Agulhon (Agulhon, P.; et al. Biomacromolecules 2012, vol. 13, pp. 1899-1907; cited in PTO-892).
As described in the above rejection under 35 U.S.C. § 112(b), the invention encompassed by claims 1-7 is unclear. For the purposes of this rejection, these claims are interpreted as a method for treating acute kidney injury by administering a drug comprising alginate oligosaccharide for treatment of acute kidney injury, wherein the alginate oligosaccharide is an alginate disaccharide, an alginate trisaccharide, or an alginate tetrasaccharide. Alternatively, if claims 1-7 are intended to be drawn to a method for preparing a drug for treating acute kidney injury, then the alginate oligosaccharide composition of Murota described below would reasonably satisfy the requirements of said drug.
Murota teaches as described in the above rejections under 35 U.S.C. § 102 and 35 U.S.C. § 103.
Murota does not teach a method for treating acute kidney injury, as required by claims 1-7 and 9.
Wong teaches a study of acute kidney injury (AKI) in patients with cirrhosis, specifically evaluating whether baseline serum creatinine levels has an effect on the course of acute kidney injury and patient survival (p. 1103, Abstract, Objectives section, lines 1-5).
Wong teaches their study included 653 hospitalized cirrhotics, and the incidence of AKI was 47% of enrolled patients. Wong teaches that patients with higher baseline serum creatinine level were more likely to develop AKI, with significantly higher delta and peak serum creatinine than the other groups, more likely to have a progressive AKI course, and associated with a significantly reduced 30-day survival (p. 1103, Abstract, Results section, lines 1-5).
Wong concludes from their study that admitted cirrhotic patients with higher baseline serum creatinine levels are at higher risk for in-hospital development of AKI and more likely to have AKI progression with reduced survival (p. 1103, Abstract, Conclusions section, lines 1-2).
Specifically regarding AKI as induced by infection, Wong teaches that 193 patients were either admitted or developed a bacterial infection during their hospitalization (p. 1106, left column, second paragraph, lines 1-3). Wong teaches that significantly more infected than non-infected patients developed stage 1 AKI, and infected patients with AKI had a greater increase in their serum creatinine levels, leading to a significantly higher peak serum creatinine during their hospitalization, although the AKI course was not significantly different between the infected and non-infected patients (p. 1106, left column, second paragraph, line 6 to right column, line 2) (emphasis added). Wong concludes that hospitalized patients with a high baseline serum creatinine levels should have their renal function monitored frequently for the development of AKI, especially in the setting of bacterial infection (p. 1109, right column, third full paragraph, lines 9-12).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the present application to administer the alginate oligosaccharide taught by Murota for the purposes of treating an acute kidney injury, including acute kidney injury induced by bacterial infection. One of ordinary skill in the art would have been motivated to administer the alginate oligosaccharide taught by Murota for the purposes of treating an acute kidney injury, including acute kidney injury induced by bacterial infection, because Murota teaches their alginate oligosaccharide product for inhibiting deterioration of renal function, including improving creatinine clearance and reducing urinary protein levels, and because Wong teaches that cirrhotic patients with higher baseline serum creatinine are at higher risk for in-hospital development of AKI, and are more likely to have AKI progression with reduced survival. Therefore, one of ordinary skill in the art would have considered practicing the method of Murota on a cirrhotic patient with elevated serum creatinine levels and AKI, because the method of Murota would be reasonably expected to reduce creatinine levels by improving creatinine clearance, which would be expected to reduce AKI progression and increase the likelihood of survival.
Moreover, because Wong teaches that hospitalized patients with high baseline serum creatinine levels should have their renal function monitored frequently for the development of AKI, especially in the setting of bacterial infection, and Murota’s method is drawn to inhibiting deterioration of renal function, one of ordinary skill in the art would have reasonably considered practicing the method of Murota on hospitalized patients with a high baseline serum creatinine levels that have declining renal function and have developed AKI.
Regarding the acute kidney injury as induced by infection, because Wong teaches that significantly more infected than non-infected patients developed stage 1 AKI, the patient population taught by Wong is reasonably considered to include patients in which AKI is induced by infection. Moreover, because infected patients with AKI had a greater increase in their serum creatinine levels, one of ordinary skill in the art would have reasonably considered a treatment for said patients that has been shown to reduce serum creatinine levels, such as the method of Murota, because reducing serum creatinine levels in these patients may reduce profession of AKI and increase likelihood of survival.
Regarding the specific alginate disaccharides, trisaccharides, and tetrasaccharides required by claims 2-5 and the salt of claim 6, Murota teaches their alginate oligosaccharide as including, for example, D-G, D-M, D-G-G, D-M-G, D-M-M, and D-G-G-G (p. 6, [0085]-[0094]), which satisfy the products required by claims 2-5. In addition, Murota teaches salts of their alginate oligosaccharides, including metal salts of alginate oligosaccharide, such as sodium alginate oligosaccharide, potassium alginate oligosaccharide, calcium alginate oligosaccharide, and mixtures thereof (p. 2, [0030], lines 1-4). As stated above, Murota teaches the sugar represented by D, as shown in formula (I) (p. 2, [0012]), which has the requirements of the monosaccharide Δ recited in the present claims.
Regarding the specific 1,4-linkages of the alginate oligosaccharides, as evidence, Agulhon teaches alginate is a polysaccharide of (1→4) linked α-L-guluronate (G) and β-D-mannuronate (M) (p. 1899, Introduction, lines 1-2). Therefore, the alginate oligosaccharides generated by treatment with alginate lyase possess the required (1→4) linkages, and the alginate disaccharides, trisaccharides, and tetrasaccharides of Murota thus would satisfy the limitations of the alginate oligosaccharides of claims 1-7 and 9.
Therefore the invention taken as a whole is prima facie obvious.
Claims 1-6 and 9 are rejected under 35 U.S.C. 103 as being unpatentable over Mirshafiey (Mirshafiey, A.; et al. Vascular Pharmacology 2005, vol. 43, pp. 30-35; cited in IDS received October 30, 2024) in view of Murota (Publication no. US 2012/0058967 Al; cited in IDS received May 1, 2025) and Pesce (Pesce, F.; et al. Frontiers in Medicine 2021, vol. 7, article 582272; cited in PTO-892), as evidenced by Agulhon (Agulhon, P.; et al. Biomacromolecules 2012, vol. 13, pp. 1899-1907; cited in PTO-892).
Pesce was published March 2, 2021, and thus is eligible as prior art under 35 U.S.C. 102(a)(1).
As described in the above rejection under 35 U.S.C. § 112(b), the invention encompassed by claims 1-6 is unclear. For the purposes of this rejection, these claims are interpreted as a method for treating acute kidney injury by administering a drug comprising alginate oligosaccharide for treatment of acute kidney injury, wherein the alginate oligosaccharide is an alginate disaccharide, an alginate trisaccharide, or an alginate tetrasaccharide. Alternatively, if claims 1-6 are intended to be drawn to a method for preparing a drug for treating acute kidney injury, then the alginate oligosaccharide composition of Murota described below would reasonably satisfy the requirements of said drug.
Mirshafiey teaches the therapeutic efficacy of sodium alginate in experimental immune complex glomerulonephritis. Mirshafiey teaches that bovine serum albumin (BSA) nephritis was induced in rats by a subcutaneous immunization and daily intravenous administration of BSA. Mirshafiey teaches sodium alginate at two different doses (25 and 50 mg/kg) was administered intraperitoneally at regular 72-h intervals for 6 weeks (p. 30, Abstract, lines 1-3).
Mirshafiey teaches the results of their experiment showed treatment with sodium alginate could significantly reduce the urinary protein excretion and serum creatinine in treated rats compared with nontreated controls (p. 30, Abstract, lines 8-9). Mirshafiey teaches a dose-dependent decrease in serum creatinine levels compared with the patient sample administered BSA but no sodium alginate (p. 33, Table 1).
Mirshafiey concludes by stating that these results suggest treatment with sodium alginate as a new immunosuppressive agent can reduce proteinuria, inhibit MMP-2 activity and suppress the antibody production as well as the development of glomerular lesions in a rat model of immune complex glomerulonephritis (p. 30, Abstract, lines 12-14).
Mirshafiey does not teach a method for treating acute kidney injury with the claimed alginate disaccharides, trisaccharides, and tetrasaccharides, as required by claims 1-6 and 9.
Murota teaches as described in the above rejections under 35 U.S.C. § 102 and 35 U.S.C. § 103.
Pesce teaches that glomerulonephritis accounts for about 10% of acute kidney injury (AKI) in adults, and that AKI episodes in glomerular disease are usually due to rapidly progressive glomerulonephritis (RPGN), in which the renal function declines over days or weeks (p. 2, left column, second paragraph, lines 1-4). Pesce teaches that AKI is based on standard
criteria such as serum creatinine and/or urine output, among other biomarkers used or proposed to be used for characterizing AKI (p. 2, left column, lines 2-5).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the present application to substitute the sodium alginate taught by Mirshafiey for treating glomerulonephritis with the sodium alginate oligosaccharides taught by Murota. One of ordinary skill in the art would have been motivated to substitute the sodium alginate taught by Mirshafiey for treating glomerulonephritis with the alginate oligosaccharides taught by Murota because Mirshafiey teaches sodium alginate for treating glomerulonephritis, including teaching a reduction in serum creatinine levels to subjects administered sodium alginate, and Murota teaches sodium alginate oligosaccharide for inhibiting deterioration of renal function and that improves creatinine clearance. Therefore, one of ordinary skill in the art would have reasonably considered substituting sodium alginate with sodium alginate oligosaccharides when treating glomerulonephritis, because the sodium alginate oligosaccharides of Murota would be expected to reduce serum creatinine levels and inhibit deterioration of renal function, and thus may also be an effective treatment for glomerulonephritis. Moreover, because the sodium alginate oligosaccharide is effectively a digested sodium alginate, and because the sodium alginate oligosaccharide is recognized by Murota for inhibiting renal deterioration, one of ordinary skill in the art would have reasonably expected sodium alginate oligosaccharide to be an effective substitute for sodium alginate when treating glomerulonephritis, absent evidence to the contrary.
Regarding the method obvious over Mirshafiey in view of Murota for treating acute kidney injury, because Pesce teaches that glomerulonephritis accounts for about 10% of acute AKI in adults, glomerulonephritis is reasonably considered as one example of AKI. In addition, because Mirshafiey and Murota teach methods that reduce creatinine levels and Pesce teaches AKI is based on standard criteria that includes creatinine output, one of ordinary skill in the art would have reasonably considered applying the method obvious over Mirshafiey in view of Murota to treat AKI with elevated serum creatinine levels.
Regarding the specific alginate disaccharides, trisaccharides, and tetrasaccharides required by claims 2-5 and the salt of claim 6, Murota teaches their alginate oligosaccharide as including, for example, D-G, D-M, D-G-G, D-M-G, D-M-M, and D-G-G-G (p. 6, [0085]-[0094]), which satisfy the products required by claims 2-5. In addition, Murota teaches salts of their alginate oligosaccharides, including metal salts of alginate oligosaccharide, such as sodium alginate oligosaccharide, potassium alginate oligosaccharide, calcium alginate oligosaccharide, and mixtures thereof (p. 2, [0030], lines 1-4). As stated above, Murota teaches the sugar represented by D, as shown in formula (I) (p. 2, [0012]), which has the requirements of the monosaccharide Δ recited in the present claims.
Regarding the specific 1,4-linkages of the alginate oligosaccharides, as evidence, Agulhon teaches alginate is a polysaccharide of (1→4) linked α-L-guluronate (G) and β-D-mannuronate (M) (p. 1899, Introduction, lines 1-2). Therefore, the alginate oligosaccharides generated by treatment with alginate lyase possess the required (1→4) linkages, and the alginate disaccharides, trisaccharides, and tetrasaccharides of Murota thus would satisfy the limitations of the alginate oligosaccharides of claims 1-6 and 9.
Therefore the invention taken as a whole is prima facie obvious.
Claim 7 is rejected under 35 U.S.C. 103 as being unpatentable over Mirshafiey (Mirshafiey, A.; et al. Vascular Pharmacology 2005, vol. 43, pp. 30-35; cited in IDS received October 30, 2024) in view of Murota (Publication no. US 2012/0058967 Al; cited in IDS received May 1, 2025) and Pesce (Pesce, F.; et al. Frontiers in Medicine 2021, vol. 7, article 582272; cited in PTO-892), as evidenced by Agulhon (Agulhon, P.; et al. Biomacromolecules 2012, vol. 13, pp. 1899-1907; cited in PTO-892) as applied to claims 1-6 and 9 above, and further in view of Naicker (Naicker, S.; et al. Seminars in Immunopathology 2007, vol. 29, 397-414; cited in PTO-892).
Mirshafiey, Murota, and Pesce teach as described in the above rejections under 35 U.S.C. § 102 and 35 U.S.C. § 103.
Mirshafiey, Murota, and Pesce do not teach treating acute kidney injury induced by hypoperfusion, infection, or renal toxicity of a drug, as recited in claim 7.
Naicker teaches that glomerular injury, occurring either as primary glomerular disease or as part of a systemic disease process, is usually a result of immune-mediated mechanisms (p. 397, Abstract, lines 1-3). Naicker teaches the mechanisms of glomerular immune deposit formation include trapping of circulating antigen–antibody complexes and the in situ formation of immune complexes within the glomerulus (p. 397, Abstract, lines 8-11). Naicker teaches that patients with streptococcal infections, Hepatitis B virus, or Hepatitis C virus infection may develop a spectrum of glomerulonephritides, which are predominantly immune-complex-mediated, and that therapy for glomerular diseases due to HIV, hepatitis B, or C virus
infections remains a challenge (p. 397, Abstract, lines 24-29).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the present application to practice the method of treating acute kidney injury due to glomerulonephritis, obvious over Mirshafiey in view of Murota and Pesce, on a patient with glomerulonephritis induced by infection. One of ordinary skill in the art would have been motivated to practice the method of treating acute kidney injury due to glomerulonephritis, obvious over Mirshafiey in view of Murota and Pesce, on a patient with glomerulonephritis induced by infection. because Mirshafiey, Murota, and Pesce render obvious a method of treating glomerulonephritis by administering the alginate oligosaccharides of claim 1, as described above, and because Naicker teaches that patients with Streptococcal infections, Hepatitis B virus, or Hepatitis C virus infection may develop a spectrum of glomerulonephritides, which are predominantly immune-complex-mediated. Therefore, one of ordinary skill in the art would have reasonably considered glomerulonephritis induced by Streptococcal infections, Hepatitis B virus, or Hepatitis C virus infection as a disease that may be treated with the method obvious over Mirshafiey in view of Murota and Pesce.
Moreover, because Mirshafiey teaches sodium alginate can suppress the antibody production as well as the development of glomerular lesions in a rat model of immune complex glomerulonephritis, and Naicker teaches that patients with Streptococcal infections, Hepatitis B virus, or Hepatitis C virus infection may develop a spectrum of glomerulonephritides which are predominantly immune-complex-mediated, the method obvious Mirshafiey in view of Murota and Pesce would reasonably apply to glomerulonephritis due to infection, because each of the model glomerulonephritis of Mirshafiey and glomerulonephritis due to infection involve immune-mediated mechanisms affecting the glomerulus, and thus a treatment effective in a model of immune complex glomerulonephritis would also be expected to be effective in treating glomerulonephritis due to infection.
Therefore the invention taken as a whole is prima facie obvious.
Conclusion
No claims are allowed.
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/B.M.B./ Examiner, Art Unit 1693
/ANDREA OLSON/ Primary Examiner, Art Unit 1693