CTNF 18/286,682 CTNF 84758 DETAILED ACTION Notice of Pre-AIA or AIA Status 07-03-aia AIA 15-10-aia 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 § 103 07-06 AIA 15-10-15 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. 07-20-aia AIA 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. 07-23-aia AIA 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. 07-20-02-aia AIA 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. 07-21-aia AIA Claim (s) 1-6, 15-16, 18, 21-25 is/are rejected under 35 U.S.C. 103 as being unpatentable over Vodyanoy et al, (US 20070122799) . Regarding claim 1, Vodyanoy et al teach a method for detecting the presence or absence of misfolded polypeptides in a sample (Para. 0008), said method comprising: (a) amplifying said sample under conditions where said misfolded polypeptides, when present, form fibrils (Para. [0008] subjecting the sample to heat or pressure, or by carrying out various numbers of seeding steps; Para. 0315: Fibril are created during the amplification step). ; (b) contacting said sample with a solution containing nanoparticles (Para. 0006,0008, 0010: metallic nanoparticle); (c) detecting said fibrils in said solution containing said nanoparticles (Para. 0252, 0320, 0061: antibody recognizes amplified misfolded prions. Para. 0315: Fibril are created during the amplification step); (d) identifying said sample as having said presence of said misfolded polypeptides if said fibrils are detected (Para. 0061: antibody detects the misfolded prion proteins include the fibrils); and (e) identifying said sample as lacking said misfolded polypeptides if said fibrils are not detected (Para. 0061: antibody not detecting the misfolded prions when prion proteins are normal). Vodyanoy do not explicitly provide the identifying step as detecting the fibrils. Vodyanoy teach the misfolded prions include the fibrils and are detected. It is desirable to detect the fibrils as they represent the presence of the amplified misfolded prions. Combining prior art elements according to known methods to yield predictable results is known. Therefore it would have been obvious to one of ordinary skill in the art to combine the detection of fibrils to provide the above advantage of detecting the amplified misfolded prions. Regarding claim 2, Vodyanoy et al teach a method for detecting the presence or absence of misfolded polypeptides in a sample, said method comprising: (a) amplifying said sample under conditions where said misfolded polypeptides, when present, form globular polypeptide aggregates (Para. [0008] subjecting the sample to heat or pressure, or by carrying out various numbers of seeding steps, aggregation may be covalent modification of the disease protein oligomeric (globular) intermediate may form); (b) contacting said sample with a solution containing nanoparticles (Para. 0006,0008, 0010: metallic nanoparticle); (c) detecting said globular polypeptide aggregates in said solution containing said nanoparticles (Para. 0252, 0320, 0061: antibody recognizes amplified misfolded prions that include the globular polypeptide aggregates); (d) identifying said sample as having said presence of said misfolded polypeptides if said globular polypeptide aggregates are detected (Para. 0061: antibody detects the misfolded prion proteins include the globular polypeptide aggregates); and (e) identifying said sample as lacking said misfolded polypeptides if said globular polypeptide aggregates are not detected (Para. 0061: antibody not detecting the misfolded prions when prion proteins are normal). Vodyanoy do not explicitly provide the identifying step as detecting the globular polypeptide aggregates. Vodyanoy teach the misfolded prions include the globular polypeptide aggregates and are detected (Para. 0252, 0320, 0061). It is desirable to detect the globular polypeptide aggregates as they represent the presence of the amplified misfolded prions. Combining prior art elements according to known methods to yield predictable results is known. Therefore it would have been obvious to one of ordinary skill in the art to combine the detection of fibrils to provide the above advantage of detecting the amplified misfolded prions. Regarding claim 3, Vodyanoy et al teach said sample is a biological sample (Para. 0058). Regarding claim 4, Vodyanoy et al teach said biological sample is obtained from a living mammal. (Para. 0058) Regarding claim 5, Vodyanoy et al teach said living mammal is selected from the group consisting of humans, monkeys, camels, horses, mink, cats, cows, sheep, mice, rats, hamsters, brocket, chital, elk, fallow deer, marsh deer, mule deer, muntjac, moose, pampas deer, red deer, reindeer, roe deer, sambar deer, sika, white-tailed deer, antelope, and goats. (Para. 0058 cattle) Regarding claim 6, Vodyanoy et al teach said biological sample is selected from the group consisting of lymph tissue, muscle tissue, tonsil tissue, skin tissue, brain tissue, brain-stem tissue, blood, cerebrospinal fluid, urine, feces, saliva, mucus, liver tissue, heart tissue, intestinal tissue, spleen tissue, and eye tissue. (Para. 0178: blood, cerebrospinal, lymph) Regarding claim 15, Vodyanoy et al teach said method comprises, prior to said amplifying step, isolating polypeptides from said sample. (Para. 0283: filtered) Regarding claim 16, Vodyanoy et al teach said amplifying step comprises shaking said sample or sonicating said sample. (Para. 0283: sonicate) Regarding claim 18, Vodyanoy et al teach said method nanoparticles are selected from the group consisting of silver nanoparticles, copper nanoparticles, platinum nanoparticles, iron nanoparticles, and any alloys thereof. (Para. 0010: copper nanoparticle) Regarding claim 21, Vodyanoy et al teach said misfolded polypeptide is selected from the group consisting of prion protein (PrP) polypeptides, tau polypeptides, amyloid ß polypeptides, α-synuclein polypeptides, and TDP-43 polypeptides. (Para. 0012) Regarding claim 22, Vodyanoy et al teach the misfolded polypeptide is associated with a proteinopathy. (para. 0012) Regarding claim 23, Vodyanoy et al teach said proteinopathy is selected from the group consisting of chronic wasting disease (CWD), Creutzfeldt-Jakob Disease, transmissible mink encephalopathy, feline spongiform encephalopathy, ungulate spongiform encephalopathy, bovine-spongiform encephalapothy, camilid spongiform encephalopathy, pituitary pars intermedia dysfunction (PPID), Alzheimer's Disease (AD), Parkinson's Disease (PD), Pick's disease, Lewy body dementia (LBD), amyotrophic lateral sclerosis (ALS), multiple systems atrophies, progressive supranuclear palsies, corticobasal degenerations, and chronic traumatic encephalopathies. (para. 0012) Regarding claim 24, Vodyanoy teach a method for detecting the presence or absence of misfolded polypeptides in a sample, wherein said method comprises: (a) amplifying said sample under conditions where said misfolded polypeptides, when present, form fibrils (Para. [0008] subjecting the sample to heat or pressure, or by carrying out various numbers of seeding steps; Para. 0315: Fibril are created during the amplification step); (b) contacting said sample with a solution containing an organic dye (Para. 0059: congo red); (c) detecting the misfolded proteins in said solution containing said organic dye; (Para. 0059: congo red) (d) identifying said sample as having said presence of said misfolded polypeptides ; and (e) identifying said sample as lacking said misfolded polypeptides. Vodyanoy do not explicitly provide the identifying step as detecting the fibrils. Vodyanoy teach the misfolded prions include the fibrils and are detected. It is desirable to detect the fibrils as they represent the presence of the amplified misfolded prions. Combining prior art elements according to known methods to yield predictable results is known. Therefore it would have been obvious to one of ordinary skill in the art to combine the detection of fibrils to provide the above advantage of detecting the amplified misfolded prions. Regarding claim 25, Vodyanoy teach a method for detecting the presence or absence of misfolded polypeptides in a sample, wherein said method comprises: (a) amplifying said sample under conditions where said misfolded polypeptides, when present, form globular polypeptide aggregates (Para. [0008] subjecting the sample to heat or pressure, or by carrying out various numbers of seeding steps; Para. 0315: Fibril are created during the amplification step); (b) contacting said sample with a solution containing an organic dye (Para. 0059: congo red); (c) detecting said globular polypeptide aggregates in said solution containing said organic dye(Para. 0059: congo red); (d) identifying said sample as having said presence of said misfolded polypeptides; and (e) identifying said sample as lacking said misfolded polypeptides. Vodyanoy do not explicitly provide the identifying step as detecting the globular polypeptide aggregates. Vodyanoy teach the misfolded prions include the globular polypeptide aggregates and are detected (Para. 0252, 0320, 0061). It is desirable to detect the globular polypeptide aggregates as they represent the presence of the amplified misfolded prions. Combining prior art elements according to known methods to yield predictable results is known. Therefore it would have been obvious to one of ordinary skill in the art to combine the detection of fibrils to provide the above advantage of detecting the amplified misfolded prions . 07-21-aia AIA Claim (s) 7-8 is/are rejected under 35 U.S.C. 103 as being unpatentable over Vodyanoy et al, (US 20070122799) in view of Osterholm et al, "Chronic Wasting Disease in Cervids: Implications for Prion Transmission to Humans and Other Animal Species, " mBio, July 2019, 10(4): e01091-19 . Regarding claim 7, Vodyanoy et al teach a method can be adapted for an antemortem diagnostic of prions (Para. 0252). Vodyanoy teach using tissue that would be difficult to obtain antemortem (Para. 0057: tissue from brain). Vodyanoy does not explicitly state said biological sample is obtained from a mammal post-mortem. Osterholm is in the art of prion (Abstract) and teaches a biological sample obtained from a mammal post-mortem (Pg. 3, last paragraph, To determine if a cervid is infected with CWD [Chronic Wasting Disease] prions postmortem tests that detect the presence of abnormal, prion proteins in the obex area of the brain stem; Pg. 5, fourth paragraph, cervid PrPC may be more prone to misfolding). It is desirable to detect the sample from a mammal post-mortem to correlate the protein disorder that may have caused death in mammals. Combining prior art elements according to known methods to yield predictable results is known. Therefore it would have been obvious to one of ordinary skill in the art to combine the said biological sample is obtained from a mammal post-mortem of Osterholm to provide the above advantage of correlate the protein disorder that may have caused death in mammals. Regarding claim 8, Vodyanoy et al teach said biological sample is beef or venison. (Vodyanoy: Para. 0058 cattle) 07-21-aia AIA Claim (s) 17 and 19-20 is/are rejected under 35 U.S.C. 103 as being unpatentable over Vodyanoy et al, (US 20070122799) in view of Zhang et al, "Gold nanoparticles as a label-free probe for the detection of amyloidogenic protein" Talanta, Volume 89, 30 January 2012, Pages 401-406 . Regarding claims 17 and 19, Vodyanoy et al teach metal nanoparticles (Para. 0010: copper nanoparticle), but are silent to said metal nanoparticles are gold nanoparticles; said detecting step comprises visually detecting a color shift, wherein said color shift is indicative of the absence of said misfolded polypeptide; said detecting step comprises detecting light absorbance, wherein an absorbance of from about 510 nm to about 521 nm is indicative of the presence of said misfolded polypeptide, and wherein an absorbance of from about 525 nm to about 600 nm is indicative of the absence of said misfolded polypeptide. Zhang et al teach using Gold nanoparticles for detecting of prion proteins changing color from red to blue (Abstract: AuNP with PrP red to blue, 700nm absence to 450nm presence). It is advantageous to provide a metal nanoparticle that provides a color shift when the prion protein is detected. Simple substitution of one known element for another to obtain predictable results is held to be obvious. Therefore, it would have been obvious to one of ordinary skill in the art to substitute the gold nanoparticle of Zhang to provide the above advantage of providing a detectable color shift when the prior protein is detected. Regarding claim 20, Vodyanoy/Zhang teach shifting of the absorbance from the absence in the red range about 700nm to the blue range 450nm in the presence of the prion. In re Boesch (205 USPQ 215) teaches the optimization of a result effective variable is ordinarily within the skill of the art. A result effective variable is one that has well known and predictable results. The choice of a range where the color shift indicates the presence or absence of the prion is a result effective variable that gives the well known and expected results of indicating the presence or absence of the prion. In the absence of a showing of unexpected results, the Office maintains the wherein an absorbance of from about 510 nm to about 521 nm is indicative of the presence of said misfolded polypeptide, and wherein an absorbance of from about 525 nm to about 600 nm is indicative of the absence of said misfolded polypeptide would have been within the skill of the art as optimization of a results effective variable . 07-21-aia AIA Claim (s) 9-12 is/are rejected under 35 U.S.C. 103 as being unpatentable over Vodyanoy et al, (US 20070122799) in view of Nickols et al, "Detection of protease-resistant cervid prion protein in water from a CWD-endemic area" Prion. 2009 Jul-Sep;3(3):171–183 . Regarding claims 9-12, Vodyanoy et al are silent to the sample is an environmental sample; said environmental sample is selected from soil, water, dust, and plants.(water); said environmental sample is obtained using a swab or a filter; said environmental sample is obtained from a location selected from group consisting of a natural habitat, a waterway, a farm, a food processing facility, a water-treatment facility, and a hospital. Nickols et al teach detection of prion proteins in environmental samples selected from soil, water, dust, and plants.(Abstract: water); said environmental sample is obtained using a swab or a filter. (Fig. S4: obtained using a filter); said environmental sample is obtained from a location selected from group consisting of a natural habitat, a waterway, a farm, a food processing facility, a water-treatment facility, and a hospital (Fig. S4: water treatment facility). It is desirable to detect prions in water samples from filters in water treatment plants to detect any accumulation of prions in the environment to reduce possible transmission of prion diseases such as chronic wasting disease (Abstract). Simple substitution of one known element for another to obtain predictable results is held to be obvious. Therefore, it would have been obvious to one of ordinary skill in the art to substitute the samples of Vodyanoy et al with the samples of Nickols to provide the above advantage of detecting any accumulation of prions in the environment to reduce possible transmission of prion diseases such as chronic wasting disease. Conclusion Any inquiry concerning this communication or earlier communications from the examiner should be directed to DENNIS MICHAEL WHITE whose telephone number is (571)270-3747. The examiner can normally be reached M-F 8:30am-5pm. 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If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000. /Dennis White/Primary Examiner, Art Unit 1758 Application/Control Number: 18/286,682 Page 2 Art Unit: 1758 Application/Control Number: 18/286,682 Page 3 Art Unit: 1758 Application/Control Number: 18/286,682 Page 4 Art Unit: 1758 Application/Control Number: 18/286,682 Page 5 Art Unit: 1758 Application/Control Number: 18/286,682 Page 6 Art Unit: 1758 Application/Control Number: 18/286,682 Page 7 Art Unit: 1758 Application/Control Number: 18/286,682 Page 8 Art Unit: 1758 Application/Control Number: 18/286,682 Page 9 Art Unit: 1758 Application/Control Number: 18/286,682 Page 10 Art Unit: 1758 Application/Control Number: 18/286,682 Page 11 Art Unit: 1758