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 .
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.
Claim(s) 22, 28 and 37-38 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Momose et al. (JPH 07-229902, IDS) (Momose).
Regarding claim 22, Momose discloses a stool resuspension solution (par [0020]) comprising one or more hemoglobin stabilization reagents selected from:
protoporphyrin complexed with Zn 2+;
calcium ion or magnesium ion;
a sugar or polysaccharide and, optionally, a polyvalent cation (par [0018]);
an osmolyte; and
a horseradish peroxidase (HRP) stabilization component and, optionally, a polyvalent cation.
Regarding claim 28, Momose discloses wherein the sugar is sucrose or trehalose (par [0018]).
Regarding claim 37, Momose teaches “[a] method of stabilizing hemoglobin in a stool sample” because Momose expressly states that “[t]he method for stabilizing hemoglobin of the present invention can be used for stabilizing hemoglobin in a fecal sample for the purpose of detecting fecal occult blood” and is useful for “maintaining the antigenicity of hemoglobin” (par [0019]).
Momose teaches “combining the stool sample with a stool resuspension solution of claim 22 to produce a suspension” because Momose teaches that its hemoglobin-stabilization method may be combined with known stabilization components, including “sugars such as sucrose” (par [0018]), and that the resulting hemoglobin-preservation solution may be placed in “a known feces collection container” (par [0020]). Momose further describes the resulting composition as “a fecal suspension” containing hemoglobin protected by the stabilization solution (par [0021]). Thus, Momose teaches combining feces with a sucrose-containing hemoglobin-stabilization solution satisfying claim 22 to form a fecal suspension.
Momose teaches “maintaining the suspension for a period of time” because it explains that the feces-containing collection container is transported to an examination facility by mail and that the hemoglobin-containing fecal sample is maintained during transportation and storage (par [0002] [0003]). Momose also experimentally prepares hemoglobin-containing fecal suspensions and stores the suspensions at 37°C for periods of up to 24 hours while monitoring the residual hemoglobin (par [0029]).
Accordingly, Momose teaches combining a stool sample with the sucrose-containing stool resuspension solution of claim 22 to produce a suspension and maintaining that suspension for a period of time, thereby anticipating claim 37.
Regarding claim 38, Momose a method of analyzing a stool sample (par [0001]), comprising:
(a) receiving, from a remote location, a composition (par [0002]) comprising:
(i) a stool sample (par [0018]); and
(ii) a stool resuspension solution of claim 22 (par [0020]),
wherein the stool sample is suspended in the solution (par [0021]); and
(b) measuring the amount of hemoglobin in the composition (par [0026]-[0028]).
Claim Rejections - 35 USC § 103
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 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.
Claim(s) 25-27 is/are rejected under 35 U.S.C. 103 as being unpatentable over Momose et al. (JPH 07-229902, IDS) (Momose) in view of Christensen et al. (EP 1101412) (Christensen).
Regarding claim 25, Momose teaches the stool resuspension solution of claim 22 as discussed above. In particular, Momose teaches that its hemoglobin-stabilization method “can be combined with known stabilization techniques,” including “sugars such as sucrose,” and that the resulting hemoglobin-preservation solution may be placed in “a known fecal collection container” to stabilize hemoglobin in a fecal suspension (par [0018], [0020]).
Momose does not expressly teach “wherein the polysaccharide is a substituted or unsubstituted polygalacturonic acid.”
Christensen teaches a polysaccharide that is a substituted or unsubstituted polygalacturonic acid. Specifically, Christensen teaches that “[p]ectin is a structural polysaccharide” and that “[t]he backbone of pectin comprises α-1-4 linked galacturonic acid residues” (par [0004]). Christensen further teaches that some carboxyl groups of the galacturonic-acid residues may be esterified, that the degree of esterification may vary from 0–90%, and that pectin having no or only a few esterified groups is referred to as pectic acid (par [0005]). Thus, Christensen’s esterified pectin is a substituted polygalacturonic acid, while its substantially de-esterified pectin or pectic acid is an unsubstituted polygalacturonic acid.
Christensen also teaches using the polygalacturonic-acid polysaccharide to stabilize proteins in an aqueous solution. Christensen states that its de-esterified pectin “offers stability to proteins in an acidic environment,” identifies the acidic environment as an aqueous solution, and explains that the pectin stabilizes proteins by “surrounding the protein(s) in a blanket of negative charges, thus forming a stable emulsion” (par [0050], [0059]).
Momose and Christensen are analogous art because they contain functional similarities and both relate to stabilizing proteins in aqueous compositions. Momose expressly teaches that its hemoglobin-stabilization technique may be combined with known stabilizers and that “a better stabilizing effect can be expected” from such a combination (par [0032]). One of ordinary skill in the art would therefore have been motivated to include Christensen’s protein-stabilizing pectin in Momose’s stool-hemoglobin preservation solution to provide additional stabilization of hemoglobin, which is a protein, as suggested by Christensen’s express teaching that the pectin stabilizes proteins in aqueous solutions. Accordingly, the modified stool resuspension solution comprises a polysaccharide that is a substituted or unsubstituted polygalacturonic acid, as required by claim 25.
Regarding claim 26, Momose in view of Christensen teaches “wherein the substituted or unsubstituted polygalacturonic acid is α-(1-4)-linked D-galacturonic acid.” Christensen teaches that “[p]ectin is a structural polysaccharide” and that “[t]he backbone of pectin comprises α-1-4 linked galacturonic acid residues.” Christensen further explains that these α-1-4-linked chains constitute the “smooth” regions of pectin and that the carboxyl groups of the galacturonic-acid residues may be esterified, thereby providing substituted or unsubstituted forms of the polygalacturonic-acid backbone. Pectin’s galacturonic-acid backbone is the conventional α-(1→4)-linked D-galacturonic-acid backbone.
Accordingly, Christensen’s pectin is a substituted or unsubstituted polygalacturonic acid comprising α-(1→4)-linked D-galacturonic-acid residues, as required by claim 26.
Regarding claim 27, Momose in view of Christensen teaches “wherein the substituted or unsubstituted polygalacturonic acid is at a concentration in the range of 0.005% to 0.5% or 0.01% to 0.125%.” Christensen teaches preparing aqueous pectin solutions and expressly states that “the pectins were tested in concentrations of 0.1%–0.25%.” (par [0317]).
Christensen’s disclosed 0.10% pectin concentration falls within both claimed ranges of 0.005–0.5% and 0.01–0.125%. Therefore, Christensen expressly teaches the concentration limitation of claim 27, and no result-effective-variable or routine-optimization rationale is necessary.
Claim 29 is rejected under 35 U.S.C. § 103 as being unpatentable over Momose et al. (JPH 07-229902, IDS) (Momose) in view of Bucci (US 2016/0297870).
Regarding claim 29, Momose teaches the stool resuspension solution of claim 28. Momose teaches that its hemoglobin-stabilization method may be combined with known stabilization techniques, including “sugars such as sucrose,” and that the resulting hemoglobin-preservation solution may be used by filling it into a known feces-collection container (par [0018] and [0020]).
Momose does not expressly teach that the sucrose is present “at a concentration in the range of 0.1 M to 0.5 M.”
Bucci teaches adding a disaccharide to a hemoglobin solution to produce a “hemoglobin-stabilizing agent solution” and identifies suitable disaccharides as “sucrose, trehalose, and raffinose” (par [0025]). Bucci further teaches that the stabilizing agent may be present at 20–80 mg/mL, preferably 55 mg/mL, and expressly claims a disaccharide selected from sucrose, trehalose, and raffinose at those concentrations (claims 14–16 and 18–21).
A concentration of 55 mg/mL sucrose or trehalose corresponds to approximately 0.161 M, which falls within the claimed range of 0.1 M to 0.5 M. Bucci therefore expressly teaches a claimed sugar at a concentration within the range recited in claim 29.
Momose and Bucci are analogous art because both relate to aqueous solutions for stabilizing hemoglobin during storage or processing. One of ordinary skill in the art would have been motivated to use Bucci’s disclosed 55 mg/mL concentration of sucrose or trehalose in Momose’s fecal-hemoglobin preservation solution to improve stabilization of the hemoglobin during storage, as suggested by Bucci’s teaching that the disaccharide is added to form a hemoglobin-stabilizing solution and that a 55 mg/mL trehalose formulation preserved the hemoglobin without producing ferric forms after lyophilization and reconstitution.
Claims 30-31 are rejected under 35 U.S.C. § 103 as being unpatentable over Momose et al. (JPH 07-229902, IDS) (Momose) in view of Di Domenico et al., (Biochemical Engineering Journal, 2002) (Di Domenico).
Regarding claim 30, Momose teaches the stool resuspension solution of claim 22 for the reasons discussed above. Momose does not expressly teach “wherein the osmolyte is betaine or trimethylamine N-oxide.”
Di Domenico teaches betaine as an osmolyte for stabilizing hemoglobin. Specifically, Di Domenico investigates “the naturally occurring osmolytes xylitol, glycine and betaine” and identifies betaine as “N,N,N-trimethylglycine” (page 27, par 5-6). Di Domenico further reports that “[a]ll the additives stabilized haemoglobin” (abstract) and concludes that the results “strongly validate the possibility of using these components to stabilize human haemoglobin” (page 30, par 5).
Momose and Di Domenico are analogous art because both relate to stabilizing hemoglobin in aqueous solutions during storage. One of ordinary skill in the art would have been motivated to include Di Domenico’s betaine in Momose’s stool-hemoglobin preservation solution to improve the stability of hemoglobin during storage, as suggested by Di Domenico’s express teaching that the osmolytes stabilize human hemoglobin and “could be added to the protein solution . . . during storage” (page 30). Accordingly, the modified Momose solution comprises an osmolyte that is betaine, as required by claim 30. The alternative recitation of trimethylamine N-oxide need not also be shown.
Regarding claim 31, Momose in view of Di Domenico teaches “wherein the betaine is at a concentration in the range of 2 M to 5 M.” Di Domenico expressly tests betaine at 10%, 20%, and 30% w/w, and Table 1 reports the hemoglobin-denaturation rate constants obtained at each concentration (page 29, Table 1).
Betaine has a molecular weight of approximately 117.15 g/mol. (NIST WebBook) Thus, Di Domenico’s 30% w/w formulation contains 300 g, or approximately 2.56 moles, of betaine per kilogram of solution. For an aqueous solution having a density approximately equal to or greater than 1 kg/L, that formulation corresponds to approximately 2.56 M or greater, within the claimed range of 2–5 M.
Moreover, Di Domenico expressly varies the betaine concentration and measures the resulting hemoglobin-denaturation rate, thereby recognizing betaine concentration as a result-effective variable. It would have been obvious to select and optimize the betaine concentration within the experimentally investigated high-concentration region, including approximately 2–5 M, to obtain the desired degree of hemoglobin stabilization. Accordingly, the modified Momose solution comprises betaine at a concentration within the range required by claim 31.
Claim 32 is rejected under 35 U.S.C. § 103 as being unpatentable over Momose et al. (JPH 07-229902, IDS) (Momose) in view of Yamazaki et al. (US 5,512,448) Yamazaki).
Regarding claim 32, Momose teaches the stool resuspension solution of claim 22 for the reasons discussed above. In particular, Momose teaches combining its fecal-hemoglobin stabilization system with known stabilizing components, including “sugars such as sucrose,” and using the resulting solution with a fecal suspension for immunological detection of hemoglobin. Momose further states that additional components may be used in combination so long as the analysis and stabilization of hemoglobin are not hindered.
Momose does not expressly teach “wherein the HRP stabilization component is at a concentration in the range of 1% to 20%, 5% to 15%, or 5% to 20%.”
Yamazaki teaches HRP stabilization components comprising polyethylene oxide (PEO) or polyvinyl alcohol (PVA). Yamazaki states that “the addition of polyethylene oxide (PEO) to HRP conjugate solutions greatly stabilizes its enzyme activity” (col. 1, lines 55-56) and that PVA “not only stabilizes peroxidase-antibody conjugate, but also does not affect immunoreaction at stabilizing concentrations.” (col. 1, lines 65-67) Yamazaki therefore expressly identifies PEO and PVA as HRP stabilization components compatible with immunoassays. (Patent Images)
Yamazaki further teaches:
about 2% to 10% PEO having a molecular weight of about 100,000 (col. 2, line 30-31);
about 2% to 5% PEO having a molecular weight of about 300,000 (col. 2, lines 33-35); and
about 1% to 5% PVA having a molecular weight of about 124,000–186,000 (col. 2, lines 49-52).
Yamazaki’s expressly disclosed 5% concentration falls within each of the claimed ranges: 1–20%, 5–15%, and 5–20%.
Momose and Yamazaki are analogous art because both relate to stabilizing proteinaceous components used in immunological assays during storage and handling. Momose expressly permits its fecal-hemoglobin stabilization solution to be combined with known stabilizing components, while Yamazaki teaches that PVA or PEO stabilizes HRP conjugates at ambient temperatures without adversely affecting the immunoreaction. One of ordinary skill in the art would have been motivated to include Yamazaki’s PVA or PEO in Momose’s stool resuspension solution to provide an immunoassay-compatible solution capable of preserving HRP-conjugate activity during storage and handling while avoiding interference with the subsequent immunological detection of fecal hemoglobin, as suggested by Yamazaki. The modified solution would retain Momose’s sucrose hemoglobin-stabilization reagent and additionally comprise a known HRP stabilization component at 5%, as required by claim 32.
Claims 33-34 and 39 are rejected under 35 U.S.C. § 103 as being unpatentable over Momose et al. (JPH 07-229902, IDS) (Momose) in view of Holtund et al. (WO 98/20355) (Holtund).
Regarding claim 33, Momose teaches the stool resuspension solution of claim 22 for the reasons discussed above. In particular, Momose teaches a hemoglobin-preservation solution used in a feces-collection container and having a protective action against hemoglobin in a fecal suspension. Momose also teaches that its hemoglobin-stabilization method may be combined with other stabilizing components, including “salts for adjusting ionic strength” (par [0018]–[0021]).
Momose does not expressly teach “wherein the polyvalent cation is calcium ion or magnesium ion.”
Holtund teaches an aqueous extraction or resuspension medium for fecal samples that contains calcium ion. Specifically, Holtund discloses:
“An example of the extraction medium (aqueous stock solution) was prepared as follows:
0.25 M Tris
0.25 M citric acid
2.5 M urea
0.025 M CaCl₂
1.25% bovine serum albumin (BSA)
0.05% sodium azide.”
(Example 1a, page 16).
Holtund further teaches transferring a fecal sample into a tube, adding the aqueous extraction medium, and homogenizing “the faecal sample … in the extraction medium” to produce a fecal dispersion (Example 2a, page 16-17). Holtund explains that, “[s]imultaneously, in the same faecal extract as is used for measurement of calprotectin, one may determine the concentration of other endogenous proteins such as haemoglobin,” and reports hemoglobin measurements obtained from fecal samples extracted using that method.
Momose and Holtund are analogous art because they are from the same field of endeavor and contain functional similarities. They both relate to aqueous fecal-sample solutions used to extract, preserve, and measure proteins including hemoglobin. One of ordinary skill in the art would have been motivated to include Holtund’s calcium chloride in Momose’s stool-hemoglobin preservation solution to provide a fecal-protein extraction medium having a controlled metal-ion composition and suitable for determining hemoglobin from the resulting fecal extract, as suggested by Holtund’s express use of its calcium-containing medium for fecal extraction followed by hemoglobin measurement. Accordingly, the modified stool-hemoglobin preservation solution comprises a polyvalent cation that is calcium ion, as required by claim 33. The alternative recitation of magnesium ion need not also be shown.
Regarding claim 34, Momose in view of Holtund teaches “wherein the polyvalent cation is at a concentration in the range of 5 mM to 25 mM.”
Holtund’s stock extraction medium contains 0.025 M CaCl₂, and Holtund teaches that “[t]he stock solution was diluted 2.5 times with water” before being added to the fecal sample (Example 2a, page 17).
The resulting calcium chloride concentration is:
25 mM ÷ 2.5 = 10 mM CaCl₂.
CaCl₂ dissociates to provide calcium ions at the same 10 mM concentration. Holtund’s 10 mM calcium-ion concentration falls directly within the claimed range of 5 mM to 25 mM. Accordingly, Momose in view of Holtund teaches the limitation of claim 34.
Regarding claim 39, Momose teaches the method of claim 38 for the reasons discussed above. Momose does not expressly teach “further comprising measuring the amount of one or more colorectal cancer tumor markers in the sample” in addition to measuring hemoglobin.
Holtund teaches measuring calprotectin, a colorectal-cancer tumor marker, in fecal samples. Holtund explains that “calprotectin … and as another example the protein haemoglobin, have been found in elevated amounts in the faeces of patients suffering from GI cancer” and teaches that detecting abnormal amounts of such indicator proteins has predictive and diagnostic value (Holtund, pp. 1–2).
Holtund further expressly reports “Calprotectin and hemoglobin measurements in 16 faecal samples from patients with colorectal cancer” and quantitatively measures both calprotectin and hemoglobin in the extracted fecal samples. Holtund explains that the lack of correlation between the measured amounts may result from their “independent nature as markers for cancer” (Holtund, p. 23, Table 3).
Momose and Holtund are analogous art because they are from the same field of endeavor and contain functional similarities. They both relate to preparing and analyzing fecal samples for proteins indicative of colorectal or gastrointestinal cancer. One of ordinary skill in the art would have been motivated to additionally measure Holtund’s calprotectin in Momose’s received fecal sample to obtain complementary colorectal-cancer information from two independent fecal markers, as suggested by Holtund’s teaching that calprotectin and hemoglobin are independently useful cancer markers and can both be quantitatively measured in the same fecal samples. Accordingly, the modified method further measures the amount of a colorectal-cancer tumor marker—calprotectin—as required by claim 39.
Claims 35-36 are rejected under 35 U.S.C. § 103 as being unpatentable over Momose et al. (JPH 07-229902, IDS) (Momose) in view of Lidgard et al. (US 2013/0211286, IDS) (Lidgard).
Regarding claim 35, Momose teaches the stool resuspension solution of claim 22 for the reasons discussed above. Momose does not expressly teach “wherein the solution further comprises Tris buffer, bovine serum albumin, polysorbate 20, sodium azide, sodium chloride, ethylenediaminetetraacetic acid, and gentamicin.”
Lidgard teaches a fecal-sample resuspension solution comprising each of the recited components. Specifically, Lidgard teaches that the solution “comprises Tris buffer, bovine serum albumin, Tween-20, sodium azide, sodium chloride, EDTA, and gentamicin” (par [0048]; claim 1). Tween-20 is polysorbate 20, and EDTA is ethylenediaminetetraacetic acid. Thus, Lidgard expressly teaches every additional component recited in claim 35.
Momose and Lidgard are analogous art because they are from the same field of endeavor and contain functional similarities. They both relate to stool-collection solutions used to suspend fecal samples and preserve hemoglobin or globin for subsequent fecal-occult-blood analysis. One of ordinary skill in the art would have been motivated to include Lidgard’s Tris buffer, bovine serum albumin, polysorbate 20, sodium azide, sodium chloride, EDTA, and gentamicin in Momose’s stool-hemoglobin preservation solution because Lidgard teaches that the components “break up, solubilize, and/or suspend the sample” and “stabilize, preserve, and/or protect the resulting suspension so that the analytes to be tested (e.g., globin) do not degrade or become damaged between the time the sample is acquired and the time the sample is tested” (par [0056]). One of ordinary skill in the art would therefore have been motivated to improve the ability of Momose’s stool-hemoglobin preservation solution to suspend the stool sample and protect globin between sample collection and testing, as suggested by Lidgard.
Regarding claim 36, Momose in view of Lidgard teaches “wherein the Tris buffer is at a concentration in the range of 10 mM to 50 mM Tris; the bovine serum albumin is at a concentration in the range of 5% to 20%; the polysorbate 20 is at a concentration in the range of 0.05% to 0.2%; the sodium azide is at a concentration in the range of 0.05% to 0.2%; the sodium chloride is at a concentration in the range of 50 mM to 250 mM; the ethylenediaminetetraacetic acid is at a concentration in the range of 5 mM to 20 mM; and gentamicin is at a concentration in the range of 5 µg/ml to 50 µg/ml.”
Lidgard expressly teaches the following preferred concentrations:
“20 mM Tris buffer (pH 7.4)”;
“10% bovine serum albumen”;
“0.10% Tween-20”;
“0.095% sodium azide”;
“140 mM sodium chloride”;
“10 mM EDTA”; and
“15 µg/ml gentamicin.”
(par [0049]–[0055]; claim 38).
Each disclosed concentration falls within its corresponding claimed range: 20 mM Tris is within 10–50 mM; 10% BSA is within 5–20%; 0.10% polysorbate 20 is within 0.05–0.2%; 0.095% sodium azide is within 0.05–0.2%; 140 mM sodium chloride is within 50–250 mM; 10 mM EDTA is within 5–20 mM; and 15 µg/mL gentamicin is within 5–50 µg/mL. Accordingly, Momose in view of Lidgard teaches every limitation of claim 36.
Claims 22-24 are rejected under 35 U.S.C. § 103 as being unpatentable over Fujita (JPH 05-281227, IDS) in view of Numata et al. (US 2005/0089607) (Numata).
Regarding claim 22, Fujita teaches the stool resuspension solution (par [0005]). Fujita explains that, during self-collection, “the feces may be suspended in the lysis solution” and may remain in that dissolved state for several days (par [0005]). Fujita further teaches suppressing the decrease in the antigen activity of human hemoglobin “by adding iron protoporphyrin to a test solution” and using “a test solution prepared by dissolving a test sample in a buffer solution to which iron protoporphyrin is added” (par [0007]). Fujita identifies the iron protoporphyrin as “hematin, heme or hemin” and teaches adding it to “a buffer solution for dissolving a test sample” (par [0009]).
Fujita’s Example further teaches preparing a hemin buffer containing 5 µg/mL bovine hemin, mixing the buffer with feces, suspending the feces at 0.25% to prepare a test solution, maintaining the test solution for up to seven days, and measuring the human hemoglobin therein (par [0013]–[0018]). Fujita concludes that “the stability of human hemoglobin was improved in the test solution to which bovine hemin was added” (par [0018]). Thus, Fujita teaches a stool resuspension solution containing an iron-complexed protoporphyrin for stabilizing human hemoglobin.
Fujita does not expressly teach “wherein the stool resuspension solution comprises protoporphyrin IX complexed with Zn²⁺.”
Numata teaches protoporphyrin IX complexed with Zn²⁺. Specifically, Numata teaches that “the metalloporphyrin moiety of hemoglobin and myoglobin is zinc protoporphyrin IX complex” (par [0006]). Numata further teaches that “[z]inc protoporphyrin is bound to globin at the fifth coordination site thereof to form zinc hemoglobin and zinc myoglobin” (par [0009]). Figure 1 likewise illustrates zinc protoporphyrin IX coordinated to a histidine residue of globin.
Fujita and Numata are analogous art because they are from the same field of endeavor and contain functional similarities. Both relate to metalloporphyrins that interact with hemoglobin or globin and preserve properties of the resulting hemoprotein. One of ordinary skill in the art would have been motivated to substitute Numata’s Zn²⁺-complexed protoporphyrin IX for Fujita’s iron protoporphyrin in the stool resuspension solution because Numata teaches that zinc protoporphyrin IX directly binds globin to form zinc hemoglobin and that replacing the central iron with zinc produces a pigment that is “extremely stable to oxidation and to the change of pH” (par [0009] and [0012]). Such a substitution would have predictably improved the resistance of the metalloporphyrin–globin system to oxidation and pH variations during storage.
Regarding claim 23, Fujita teaches adding the protoporphyrin at 5 µg/mL. Numata identifies zinc protoporphyrin IX as having a characteristic mass of approximately 624.20 (par [0008]). Using Zn²⁺-complexed protoporphyrin IX at Fujita’s disclosed concentration therefore corresponds to approximately:
5 mg/L ÷ 624.20 g/mol ≈ 8.0 µM.
The resulting concentration of approximately 8.0 µM falls within the claimed range of 0.1 µM to 10 µM. Accordingly, Fujita in view of Numata teaches the stool resuspension solution comprising protoporphyrin IX complexed with Zn²⁺ at the concentration required by claim 23.
Regarding claim 24, Fujita in view of Numata teaches “wherein the stool resuspension solution comprises protoporphyrin IX complexed with Zn²⁺ and the concentration of protoporphyrin IX complexed with Zn²⁺ is in the range of 1 µM to 10 µM” for the reasons discussed regarding claim 23. The resulting concentration of approximately 8.0 µM also falls directly within the narrower claimed range of 1 µM to 10 µM.
Claim 40 is rejected under 35 U.S.C. § 103 as being unpatentable over Lidgard et al. (US 2013/0211286, IDS) (Lidgard) in view of Momose et al. (JPH 07-229902, IDS) (Momose).
Regarding claim 40, Lidgard teaches “[a] sample collection device comprising: a sample collection container having an open end.” Lidgard discloses a body comprising a sample collection chamber bounded at its proximal end by a septum having an aperture, and states that “the proximal end of the body (1) is adapted to mate with a cap (12) attached to the proximal end of the sampling rod (5).” Lidgard further teaches that “[t]he sample collection chamber … is adapted to hold a solution.” Thus, Lidgard’s body and sample collection chamber constitute a sample collection container having an opening through which the sampling rod is inserted and containing a resuspension solution.
Lidgard teaches “a stool sampling rod for scooping and/or scraping a sample of stool.” Lidgard states that “rubbing and/or scraping the area comprising the metering ridges (9) on the stool to be sampled captures a mass of stool” on the distal portion of the sampling rod.
Lidgard teaches “wherein a distal end of the sampling rod is dimensioned to be inserted into the sample collection container.” Specifically, Lidgard states that “[t]he sampling rod (5) is adapted to be inserted into the body (1)” and is designed to fit through the aperture into the sample collection chamber. Lidgard further teaches that, when fully inserted, the distal portion and its metering ridge are positioned completely within the sample collection chamber and exposed to the solution contained therein.
Lidgard also teaches “the proximal end of the sampling rod is adapted to connect with the open end of the sample collection container, thereby sealing the distal end of the sampling rod within the device.” Lidgard teaches that a cap is attached to the proximal end of the sampling rod and is configured to engage the proximal end of the body. Lidgard further states that the junction between the proximal and distal portions of the rod “forms a plug or stopper that seals the aperture” when the sampling rod is fully inserted, thereby sealing the distal portion within the sample collection chamber.
Lidgard does not expressly teach that the solution within the sample collection chamber is “the stool resuspension solution of claim 22.”
Momose teaches the claimed stool resuspension solution. Momose teaches that its hemoglobin-stabilization solution may be combined with known stabilizing agents, including “sugars such as sucrose,” and that the hemoglobin-preservation solution is used “by filling it in a known feces collection container.” Momose further teaches that sucrose exhibits a stabilizing effect on hemoglobin and that the solution protects hemoglobin in a fecal suspension. Thus, Momose teaches a stool resuspension solution comprising the claimed sugar hemoglobin-stabilization reagent.
Lidgard and Momose are analogous art because they are from the same field of endeavor and contain functional similarities. They both relate to fecal-sample collection containers containing aqueous solutions for suspending and preserving stool samples for subsequent hemoglobin analysis. One of ordinary skill in the art would have been motivated to include Momose’s sucrose-containing hemoglobin-preservation solution in Lidgard’s stool sample collection device to improve preservation of fecal hemoglobin while the collected device is stored or returned by mail to a testing facility, as suggested by Momose’s teaching that hemoglobin may denature during transportation and that sucrose stabilizes hemoglobin. Lidgard likewise teaches that its solution stabilizes, preserves, and protects the fecal suspension before the mailed device is analyzed. Accordingly, the modified Lidgard device comprises the stool resuspension solution of claim 22 and every structural limitation of claim 40.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to XIAOYUN R XU, Ph. D. whose telephone number is (571)270-5560. The examiner can normally be reached M-F 8am-5pm.
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/XIAOYUN R XU, Ph.D./ Primary Examiner, Art Unit 1797
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