DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
Restriction election
In response to a requirement for restriction dated 09/03/2025, applicant elects Group I (claims 1-14) and species Group I (claims 3 and 4) without traverse per applicant response dated 10/03/2025.
Claim Status
Claims 1-17 are pending.
Claims 5 and 15-17 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a non-elected invention and species, as described above.
Claims 1-4 and 6-14 are under examination.
Claims 1-4 and 6-14 are rejected.
Priority
Applicant's claim for the benefit of a prior-filed application, PCT/IB2020/056251, filed 07/02/2020, is acknowledged.
Acknowledgment is made of applicant’s claim for foreign priority under 35 U.S.C. 119 (a)-(d) to App. No. ITALY 102019000012555, filed 07/22/2019. Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Information Disclosure Statement
The information disclosure statement (IDS) filed on 01/21/2022 is in compliance with the provisions of 37 CFR 1.97 and has therefore been considered. A signed copy of the IDS document is included with this Office Action.
Drawings
The Drawings submitted 01/21/2022 are accepted.
Claim Rejections - 35 USC § 112
35 U.S.C. 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.
Claims 8 and 12 is rejected under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor regards as the invention.
Claim 8, limitation, recites includes recitations of exemplary limitations: A1: 10-20 kDa; A2: 20-25 kDa; A3: 25-35 kDa; A4: 35-45 kDa. It is not clear if the exemplary limitations are intended to be non-limiting claim language or if they are intended to further limit the bands of molecular weight. As set forth in MPEP 2173.05(d), examples and preferences stated in the claims may lead to confusion over the intended scope of a claim.
Claim 12 recites “wherein said step b) is followed by a step b') in which the incubated material is subjected to centrifugation and one or more washes with phosphate buffer to eliminate weakly bound proteins”. The broadest reasonable interpretation of a method (or process) claim having contingent limitations requires only those steps that must be performed and does not include steps that are not required to be performed because the condition(s) precedent are not met. Claim 1 only requires 1(b) to be performed. The limitation of 1(b’) is stated s an optional step, therefore claim 12 is directed to an optional limitation. It is unclear if this limitation is required or just further limiting an optional step.
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.
Claims 1-4 and 6-14 are rejected under 35 U.S.C. 101 because the claimed invention is directed to one or more judicial exceptions without significantly more.
MPEP 2106 organizes judicial exception analysis into Steps 1, 2A (Prongs One and Two) and 2B as follows below. MPEP 2106 and the following USPTO website provide further explanation and case law citations: uspto.gov/patent/laws-and-regulations/examination-policy/examination-guidance-and-training-materials.
Framework with which to Evaluate Subject Matter Eligibility:
Step 1: Are the claims directed to a process, machine, manufacture, or composition of matter;
Step 2A, Prong One: Do the claims recite a judicially recognized exception, i.e. a law of nature, a natural phenomenon, or an abstract idea;
Step 2A, Prong Two: If the claims recite a judicial exception under Prong One, then is the judicial exception integrated into a practical application (Prong Two); and
Step 2B: If the claims do not integrate the judicial exception, do the claims provide an inventive concept.
Framework Analysis as Pertains to the Instant Claims:
Step 1
With respect to Step 1: yes, the claims are directed to method, i.e., a process, machine, or manufacture within the above 101 categories [Step 1: YES; See MPEP § 2106.03].
Step 2A, Prong One
With respect to Step 2A, Prong One, the claims recite judicial exceptions in the form of abstract ideas. The MPEP at 2106.04(a)(2) further explains that abstract ideas are defined as:
mathematical concepts (mathematical formulas or equations, mathematical relationships and mathematical calculations);
certain methods of organizing human activity (fundamental economic practices or principles, managing personal behavior or relationships or interactions between people); and/or
mental processes (procedures for observing, evaluating, analyzing/ judging and organizing information).
With respect to the instant claims, under the Step 2A, Prong One evaluation, the claims are found to recite abstract ideas that fall into the grouping of mental processes (in particular procedures for observing, analyzing and organizing information) and mathematical concepts (in particular mathematical relationships and formulas) are as follows:
Independent claim 1:
providing at least one discriminant function (f(a1,a2,...an), g(ai,a2, a3,... an)) and two or more bands of molecular weight (A1, A2...An), said at least one discriminant function (f(a1,a2,...an), g(a,,a2, a3,... an)) and said bands of molecular weight (A1, A2,....An) being predetermined on the basis of a set of reference samples;
calculating an integral area value (VA1, VA2... VAn) of said protein profile (Pp) for each of said bands of molecular weight (A1, A2... An);
calculating at least one discriminant value (VDf, VD9) of said at least one discriminant function (f(a1,a2,...an), g(ai,a2, C3,... an)) for at least one pair of said integral area values (VA1, VA2... VAn);
classifying the plasma sample by comparing said at least one discriminant value (VDf, VD9) with at least one predefined threshold value (VS).
Dependent claims 2-4, 6-11, and 14 recite further steps that limit the judicial exceptions in independent claim 1 and, as such, also are directed to those abstract ideas. For example, claim 2 further limits the examination of claim 1, claim 3 further limits the discriminant function of claim 1, claim 4 further limits the discriminant function of claim 1, claims 6 and 8 further limit the bands of molecular weight of claim 1, claim 7 further limits predefined threshold of claim 1, claim 9 further limits the gold nanoparticles of claim 1, claims 10 and 11 further limit the temperature of claim 1, and claim 14 further limits the polyacrylamide gradient of claim 1.
The abstract ideas recited in the claims are evaluated under the Broadest Reasonable Interpretation (BRI) and determined to each cover performance either in the mind and/or by mathematical operation because the method only requires a user to manually calculate and classify. Without further detail as to the methodology involved in “calculating an integral area value”, “calculating at least one discriminant value”, and “classifying the plasma sample” under the BRI, one may simply, for example, use pen and paper to classify the plasma sample.
Therefore, claim 1 and those claims dependent therefrom recite an abstract idea [Step 2A, Prong 1: YES; See MPEP § 2106.04].
Step 2A, Prong Two
Because the claims do recite judicial exceptions, direction under Step 2A, Prong Two, provides that the claims must be examined further to determine whether they integrate the judicial exceptions into a practical application (MPEP 2106.04(d)). A claim can be said to integrate a judicial exception into a practical application when it applies, relies on, or uses the judicial exception in a manner that imposes a meaningful limit on the judicial exception. This is performed by analyzing the additional elements of the claim to determine if the judicial exceptions are integrated into a practical application (MPEP 2106.04(d).I.; MPEP 2106.05(a-h)). If the claim contains no additional elements beyond the judicial exceptions, the claim is said to fail to integrate the judicial exceptions into a practical application (MPEP 2106.04(d).III).
Additional elements, Step 2A, Prong Two
With respect to the instant recitations, the claims recite the following additional elements:
Independent claim 1:
providing a plasma sample from a blood sample of a subject to be analyzed;
incubating said plasma sample with gold nanoparticles so as to allow the formation of a protein crown on said nanoparticles, said passage b) being optionally followed by a passage b') in which the incubated material is subjected to centrifugation and one or more washes with phosphate buffer to eliminate weakly bound proteins;
separating the proteins that make up said protein crown from said nanoparticles;
subjecting said proteins to electrophoresis on a denaturing polyacrylamide gradient gel so as to obtain the protein profile (Pp) of the protein crown obtained in point b) or b')
Dependent claim 12:
incubated material is subjected to centrifugation and one or more washes with phosphate buffer to eliminate weakly bound proteins.
Dependent claim 13:
is carried out by boiling for about 10 minutes the gold particles as obtained in point b) or b') suspended in polyacrylamide gel charge buffer comprising SDS.
Considerations under Step 2A, Prong Two
With respect to Step 2A, Prong Two, the additional elements of the claims do not integrate the judicial exceptions into a practical application for the following reasons. Those steps directed to producing gold nanoparticles coated with the protein crown are insignificant extra solution activity because as all they do is gather the data for the mathematical steps and do not impose any meaningful limitation on the judicial exceptions, or on how the judicial exceptions are performed. Data gathering and extra solution activitie steps are not sufficient to integrate judicial exceptions into a practical application (MPEP 2106.05(g)).
Thus, none of the claims recite additional elements which would integrate a judicial exception into a practical application, and the claims are directed to one or more judicial exceptions [Step 2A, Prong 2: NO; See MPEP § 2106.04(d)].
Step 2B (MPEP 2106.05.A i-vi)
According to analysis so far, the additional elements described above do not provide significantly more than the judicial exception. A determination of whether additional elements provide significantly more also rests on whether the additional elements or a combination of elements represents other than what is well-understood, routine, and conventional. Conventionality is a question of fact and may be evidenced as: a citation to an express statement in the specification or to a statement made by an applicant during prosecution that demonstrates a well-understood, routine or conventional nature of the additional element(s); a citation to one or more of the court decisions as discussed in MPEP 2106(d)(II) as noting the well-understood, routine, conventional nature of the additional element(s); a citation to a publication that demonstrates the well-understood, routine, conventional nature of the additional element(s); and/or a statement that the examiner is taking official notice with respect to the well-understood, routine, conventional nature of the additional element(s).
With respect to claims 1, 12 and 13 and those claims dependent therefrom, the protein crown formation, isolation and characterization elements do not rise to the level of significantly more than the judicial exception. The process of performing protein crown formation is well-understood, routine, and conventional in the art. The methods are well known and may include steps as follows incubating with gold particles, separation by centrifuge, required washing steps, and enzymatic digestion of the proteins bound to the NP surface, and their subsequent quantification with polyacrylamide gel electrophoresis as disclosed by Del Pino et al. (Del Pino, Pablo, et al. "Protein corona formation around nanoparticles–from the past to the future." Materials Horizons 1.3 (2014): 301-313, newly cited).
Taken alone, the additional elements do not amount to significantly more than the above-identified judicial exception(s). Even when viewed as a combination, the additional elements fail to transform the exception into a patent-eligible application of that exception. Thus, the claims as a whole do not amount to significantly more than the exception itself [Step 2B: NO; See MPEP § 2106.05].
Therefore, the instant claims are not drawn to eligible subject matter as they are directed to one or more judicial exceptions without significantly more. For additional guidance, applicant is directed generally to the MPEP § 2106.
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.
A. Claim(s) 1 is/are rejected under 35 U.S.C. 103 as being unpatentable over Caputo et al. (Caputo, D., et al. "A protein corona-enabled blood test for early cancer detection." Nanoscale 9.1 (2017): 349-354, cited on IDS dated 01/21/2022) in view of Zheng et al. (Zheng, Tianyu, et al. "Gold nanoparticle-enabled blood test for early stage cancer detection and risk assessment." ACS applied materials & interfaces 7.12 (2015): 6819-6827, newly cited).
Claim 1 is directed to a method to assist in the early diagnosis of pancreatic adenocarcinoma which allows the identification of subjects in an early state of disease or at risk of pancreatic adenocarcinoma for whom it is necessary or appropriate to carry out second level examinations by classifying a plasma sample of these subjects according to two or more levels of risk in which the classification of said sample in at least one of said levels of risk indicates the need or opportunity to carry out second-level examinations, comprising the following steps:
Caputo discloses a protein corona-enabled blood test for early cancer detection [title]. Caputo further discloses developing new methods for the early detection of pancreatic cancer is an urgent task for current research. To date, nanotechnology offers unprecedented opportunities for cancer therapeutics and diagnosis abstract]. Caputo also discloses the aim of this study is the development of a new pancreatic cancer diagnostic technology based on the exploitation of the nano-bio interactions between nanoparticles and blood samples [abstract]. Caputo further discloses for the two classes to be discriminate, so that a positive value of L points to class A and a negative value to class B [p. 353, col. 1, par. 2]. Caputo is silent on second-level examinations. However, early detection implies that second-level examinations will follow.
a) providing a plasma sample from a blood sample of a subject to be analyzed;
Caputo also discloses the aim of this study is the development of a new pancreatic cancer diagnostic technology based on the exploitation of the nano-bio interactions between nanoparticles and blood samples [abstract]
b) incubating said plasma sample with gold nanoparticles so as to allow the formation of a protein crown on said nanoparticles, said passage b) being optionally followed by a passage b') in which the incubated material is subjected to centrifugation and one or more washes with phosphate buffer to eliminate weakly bound proteins;
Caputo discloses the plasma sample is incubated on lipid NPs [p. 352, col. 2, par. 4].
c) separating the proteins that make up said protein crown from said nanoparticles;
Caputo discloses after incubation, liposome–protein complexes were isolated by centrifugation for 15 min at 14 000 rpm. The pellets were then washed three times with PBS to remove unbound proteins, obtaining the “hard corona” [p. 352, col. 2, par. 3].
d) subjecting said proteins to electrophoresis on a denaturing polyacrylamide gradient gel so as to obtain the protein profile (Pp) of the protein crown obtained in point b) or b');
Caputo discloses Identical volumes (10 μL) of each sample were loaded on a gradient polyacrylamide gel (4–20% Criterion TGX precast gels, Bio-Rad), and run at 100 V for about 150 minutes [p. 352, col. 2, par. 4].
e) providing at least one discriminant function (/{ai, a2, ... an), g(ai, a2, m ... an)) and two or more bands of molecular weight (A1, A2 ... An), said at least one discriminant function (/{ai, a2, ... an), (g(ai, a2, m, ... an)) and said bands of molecular weight (A1, A2, .... An) being predetermined on the basis of a set of reference samples;
Caputo discloses the second dataset was composed of 4 variables, i.e., the integral areas of the average lane intensity profiles calculated for (i) MW < 25 kDa; (ii) 25 < MW < 50; (iii) 50 < MW < 120; (iv) MW > 120 kDa [p. 353, col. 1, par. 2]. Captuo further discloses clustered and classified the patients by means of Linear Discriminant Analysis (LDA), performed on the principal components [p. 353, col. 1, par. 2]. Caputo also discloses LDA is the method of election to determine whether meaningful differences exist between the groups and to identify the discriminating power of each variable [p. 353, col. 1, par. 2]. Caputo further discloses the technique is constructed of a set of linear functions of predictors, known as discriminant functions, such that L = b1x1 + b2x2 + … + bnxn + c, where the bi are discriminant coefficients the xi are the input variables or predictors, and c is a constant [p. 353, col. 1, par. 2]. Caputo also discloses L is a class index that usually takes the values of 1 and −1, respectively, for the two classes to be discriminate, so that a positive value of L points to class A and a negative value to class B [p. 353, col. 1, par. 2].
f) calculating an integral area value (V A1, V A2 ... V An) of said protein profile (Pp) for each of said bands of molecular weight (A1, A2 ... An);
Caputo discloses to properly evaluate changes in the HC, the intensity profiles of healthy individuals (Fig. 2, panel A) and those of pancreatic cancer patients (Fig. 2, panel B) were reduced to the following four regions of molecular weight (MW): (i) MW < 25 kDa; (ii) 25 < MW < 50; (iii) 50 < MW < 120; (iv) MW > 120 kDa (Fig. S2 in the ESI†) and subsequently, the integral area was calculated for each region [p. 351, col. 1, par. 1].
g) calculating at least one discriminant value (VDr, VDg) of said at least one discriminant function (/{ai, a2, ... an), (g(ai, a2, m, ... an)) for at least one pair of said integral area values (V A1, V A2 ... V An);
h) classifying the plasma sample by comparing said at least one discriminant value (VDr, VDg) with at least one predefined threshold value (VS).
Caputo discloses the second dataset was composed of 4 variables, i.e., the integral areas of the average lane intensity profiles calculated for (i) MW < 25 kDa; (ii) 25 < MW < 50; (iii) 50 < MW < 120; (iv) MW > 120 kDa [p. 353, col. 1, par. 2]. Captuo further discloses clustered and classified the patients by means of Linear Discriminant Analysis (LDA), performed on the principal components [p. 353, col. 1, par. 2]. Caputo also discloses LDA is the method of election to determine whether meaningful differences exist between the groups and to identify the discriminating power of each variable [p. 353, col. 1, par. 2]. Caputo further discloses the technique is constructed of a set of linear functions of predictors, known as discriminant functions, such that L = b1x1 + b2x2 + … + bnxn + c, where the bi are discriminant coefficients the xi are the input variables or predictors, and c is a constant [p. 353, col. 1, par. 2]. Caputo also discloses L is a class index that usually takes the values of 1 and −1, respectively, for the two classes to be discriminate, so that a positive value of L points to class A and a negative value to class B [p. 353, col. 1, par. 2].
Caputo is silent on using gold nanoparticles.
However, Zheng discloses gold nanoparticle-enabled blood test for early stage cancer detection and risk assessment [title]. Zheng further discloses because the protein profile in the blood of cancer patients differs from healthy donors, we hypothesize that the molecular composition of the protein corona formed on the ctAuNP surface may differ between cancer and noncancer human blood [p. 6820, col, 2, par. 1]. Zheng also discloses the test detects increased immune activities in cancer patients and tumor specific autoantibodies have been found and detected in a broad spectrum of cancer types and it is possible that this new test may be able to detect other types of cancer as well [p. 6821, col. 1, par. 1].
Claim 3 is directed to the method according to claim 1, wherein said at least one discriminant function (f{ai, a2, ... an), (g(ai, a2, m, ... an)) is obtained by linear discrimination analysis.
Caputo discloses the second dataset was composed of 4 variables, i.e., the integral areas of the average lane intensity profiles calculated for (i) MW < 25 kDa; (ii) 25 < MW < 50; (iii) 50 < MW < 120; (iv) MW > 120 kDa [p. 353, col. 1, par. 2]. Captuo further discloses clustered and classified the patients by means of Linear Discriminant Analysis (LDA), performed on the principal components [p. 353, col. 1, par. 2]. Caputo also discloses LDA is the method of election to determine whether meaningful differences exist between the groups and to identify the discriminating power of each variable [p. 353, col. 1, par. 2]. Caputo further discloses the technique is constructed of a set of linear functions of predictors, known as discriminant functions, such that L = b1x1 + b2x2 + … + bnxn + c, where the bi are discriminant coefficients the xi are the input variables or predictors, and c is a constant [p. 353, col. 1, par. 2]. Caputo also discloses L is a class index that usually takes the values of 1 and −1, respectively, for the two classes to be discriminate, so that a positive value of L points to class A and a negative value to class B [p. 353, col. 1, par. 2].
Claim 4 is directed to the method according to claim 1, wherein said at least one discriminant function (f{ai, a2, ... an), (g(ai, a2, m, ... an)) comprises a first function (f(ai, a2)) represented by the equation of a straight line of the type: f (m, m) = rl + r2 * m + r3 * m = 0 in which rl, r2 and r3 are the coefficients of the line and ai and a2 are integral area values.
Caputo discloses the second dataset was composed of 4 variables, i.e., the integral areas of the average lane intensity profiles calculated for (i) MW < 25 kDa; (ii) 25 < MW < 50; (iii) 50 < MW < 120; (iv) MW > 120 kDa [p. 353, col. 1, par. 2]. Captuo further discloses clustered and classified the patients by means of Linear Discriminant Analysis (LDA), performed on the principal components [p. 353, col. 1, par. 2]. Caputo also discloses LDA is the method of election to determine whether meaningful differences exist between the groups and to identify the discriminating power of each variable [p. 353, col. 1, par. 2]. Caputo further discloses the technique is constructed of a set of linear functions of predictors, known as discriminant functions, such that L = b1x1 + b2x2 + … + bnxn + c, where the bi are discriminant coefficients the xi are the input variables or predictors, and c is a constant [p. 353, col. 1, par. 2]. Caputo also discloses L is a class index that usually takes the values of 1 and −1, respectively, for the two classes to be discriminate, so that a positive value of L points to class A and a negative value to class B [p. 353, col. 1, par. 2].
Claim 6 is directed to the method according to claim , wherein said two or more bands of molecular weight (A1, A2 ... An) are determined so that each peak - corresponding to a respective electrophoretic band of each protein profile of the set of reference samples belongs to one and only one of said bands.
Caputo discloses (A) Principal components (PC1, PC2) calculated from the four integral areas of the total lane intensity profiles calculated in the following four regions of molecular weight: (i) MW < 25 kDa; (ii) 25 < MW < 50; (iii) 50 < MW < 120; (iv) MW > 120 kDa. Blue and orange circles refer to the pancreatic cancer and healthy patients, respectively. (B) Centroids of the distributions of panel A [p. 351, fig. 3].
Claim 7 is directed to the method according to claim 1, wherein said at least one predefined threshold value (VS) is equal to zero and said plasma sample is classified as at risk if the discriminant value (VDr, VDg) is greater than zero.
Caputo discloses L is a class index that usually takes the values of 1 and −1, respectively, for the two classes to be discriminate, so that a positive value of L points to class A and a negative value to class B [p. 353, col. 1, par. 2].
Claim 8 is directed to the method according to claim 1, wherein said bands of molecular weight can be, for example, two or more among A1: 10-20 kDa; A2: 20-25 kDa; A3: 25-35 kDa; A4: 35-45 kDa.
Caputo discloses (A) Principal components (PC1, PC2) calculated from the four integral areas of the total lane intensity profiles calculated in the following four regions of molecular weight: (i) MW < 25 kDa; (ii) 25 < MW < 50; (iii) 50 < MW < 120; (iv) MW > 120 kDa. Blue and orange circles refer to the pancreatic cancer and healthy patients, respectively. (B) Centroids of the distributions of panel A [p. 351, fig. 3].
Claim 10 is directed to the method according to claim 1, wherein step b) is carried out at a temperature between 35 and 40°C for a period of time between 40 and 120 minutes.
Caputo discloses liposome–protein complexes were prepared by incubating liposomes with HP (1 : 1 v/v) at 37 °C for 1 hour [p. 352, col. 2, par. 2].
Claim 11 is directed to the method according to claim 10, wherein said temperature is 37°C and/or said time is 55 to 56 minutes.
Caputo discloses liposome–protein complexes were prepared by incubating liposomes with HP (1 : 1 v/v) at 37 °C for 1 hour [p. 352, col. 2, par. 2].
Claim 12 is directed to the method according to claim 1, wherein said step b) is followed by a step b') in which the incubated material is subjected to centrifugation and one or more washes with phosphate buffer to eliminate weakly bound proteins.
Caputo discloses after incubation, the pellets were then washed three times with PBS to remove unbound proteins, obtaining the “hard corona” [p. 352, col. 2, par. 3].
Claim 13 is directed to the method according to claim 1, wherein said separation at point c) is carried out by boiling for about 10 minutes the gold particles as obtained in point b) or b') suspended in polyacrylamide gel charge buffer comprising SOS.
Caputo discloses the HC-coated NPs were re-suspended in 20 μL of Laemmli loading buffer 1× (10 μL βME/1 mL Laemmli loading buffer) and boiled for 5 min at 100 °C [p. 352, col. 2, par. 3]. Caputo further discloses identical volumes (10 μL) of each sample were loaded on a gradient polyacrylamide gel (4–20% Criterion TGX precast gels, Bio-Rad), and run at 100 V for about 150 minutes [p. 352, col. 2, par. 3].
Claim 14 is directed to the method according to claim 1, wherein said polyacrylamide gradient is a 4-20% gradient.
Caputo discloses identical volumes (10 μL) of each sample were loaded on a gradient polyacrylamide gel (4–20% Criterion TGX precast gels, Bio-Rad), and run at 100 V for about 150 minutes [p. 352, col. 2, par. 3].
In regards to claim(s) 1, 3-4, and 6-14, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine Caputo with Zheng as they both disclose the use of nanoparticles for diagnosing cancer. The motivation would have been to modify the liposome nanoparticle of Caputo with the gold nanoparticle of Zheng the new test may be combined with other cancer type-specific test to improve the early detection and diagnosis of specific cancer types. as disclosed by Zheng [p. 6825, col. 1, par. 1]. Further it would be obvious to substitute the gold nanoparticles from Zheng into Caputo as the processing of Caputo is the same as the instant claims.
B. Claims 2 are rejected under 35 U.S.C. 103 as being unpatentable over Caputo in view of Banstola, as applied to claim 1 as above, and in further view of Miura et al. (Miura, Fumihiko, et al. "Diagnosis of pancreatic cancer." Hpb 8.5 (2006): 337-342, newly cited).
Claim 2 is directed to the method according to claim 1, wherein said second-level examinations comprise one or more among: abdomen CT, abdomen MRI, echoendoscopy, ERCP.
Caputo and Banstola are silent on a second-level examination.
However, Miura discloses diagnosis of pancreatic cancer [title]. Miura further discloses the ability to diagnose pancreatic carcinoma has been rapidly improving with the recent advances in diagnostic techniques such as contrast-enhanced Doppler ultrasound (US), helical computed tomography (CT), enhanced magnetic resonance imaging (MRI), and endoscopic US (EUS) [abstract]. It is obvious that if an early risk is detected with a blood test that a follow up diagnostic tool would be used.
In regards to claim(s) 2, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine Caputo and Banstola with Miura as they all are directed to the diagnosis of pancreatic cancer. The motivation would have been to include the second level diagnostic tools with Caputo to as recent advances in diagnostic techniques such as contrast-enhanced Doppler US, helical CT, enhanced MRI, and EUS have led to improvements in sensitivity for identifying pancreatic carcinoma as disclosed by Miura [conclusion].
Conclusion
No claims are allowed.
Inquiries
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Dawn M. Bickham whose telephone number is (703)756-1817. The examiner can normally be reached M-Th 7:30 - 4:30.
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/D.M.B./Examiner, Art Unit 1685
/Soren Harward/Primary Examiner, TC 1600