DETAILED ACTION Status of Claims: Claims 1-32 are pending. 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 Objections Claim 27 is objected to because of the following informalities: The claim contains numerous acronyms. The first instance of an acronym within the claims should be preceded by the full term. Appropriate correction is required. 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 appl icant regards as his invention. Claims 4, 5, 10, 14, 25, and 28-32 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. Regarding Claim 4: The claim states “an average particle size in a range from about 50 nm to about 100 nm… about 200 nm or less, from about 200 nm to about 1000 nm, or more than 1000nm. This limitation renders the claim indefinite because it is not clear what, if any, particles sizes are excluded from the claim. Regarding Claim 5: The claim uses commas, semicolons, and the word “or” multiple times to separate the items in the list. It is not clear how these different forms of punctuation and the would “or” are intended to break of the list of alternatives or be interpreted within the claim. Regarding Claim 10: The claim refers to “the ion exchange chromatography”. However “ion exchange” is required in the alternative in claim 9. Therefore it is not clear if claim 1 is requiring ion exchange chromatography, or only limiting the type is ion exchange chromatography functionality is present. Regarding Claim 14: The claim refers to “the functional groups” and “the porous resin”. There is insufficient antecedent basis for these limitations within the claim. Antecedent basis is provided in claim 6, however claim 14 depends form claim 1. Regarding Claim 25: The claim refers to “ the other biomaterial”. There is insufficient antecedent basis for this limitation within the claims. Regarding Claim 28: The claim states a “chromatography column configured for performing the method of claim 1”. This limitation renders the claim indefinite because it is not clear how a column can be configured for “providing a sample” or “providing…a multimodal chromatography resin”. Regarding Claim 29: The claim refers to “a multimodal chromatography resin”. However claim 1 already provides antecedent basis for this limitation. It is therefore not clear if claim 29 requires an additional multimodal chromatography resin or not. Regarding Claim 30 : The claim states “the kit comprising…instructions for carrying out the method of claim 1”. This limitation renders the claim indefinite because it is not clear what “instruction for carrying out the method of claim 1” is limited to. Specifically it is not clear limited to the steps (a), (b), and (c) or claim 1 or directions on how those steps are performed. Regarding Claim 31: The claim states “providing a sample…and a chromatography column comprising a multimodal chromatography resin…performing the method of claim 1…” However claim 1 requires “providing a sample…and a multimodal chromatography resin”. It is therefore not clear if this is an additional step or the same step. Claim 32 is indefinite as it depends form claim 31. 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) 1 -7, 16 , 21-24 , 26 -28 is/are rejected under 35 U.S.C. 102 (a)(1) as being anticipated by Noyes et al (US 2022/0387906) . Regarding Claim 1: Noyes teaches the method of isolating and/or purifying a nanoparticulate biomaterial (nano carriers such as EV) (see para. 0005) , the method comprising the steps of:(a) providing a sample comprising the nanoparticulate biomaterial (samples comprising EVs) and a multimodal chromatography resin (multi-modal chromatography) (see para. 0246) , wherein the sample comprises said nanoparticulate biomaterial suspended in an aqueous liquid (3D suspension culture media, culture media is aqueous) (see para. 0274, 0279. 0511) ; and (b) contacting the sample with the multimodal chromatography resin for an incubation period (flow through, therefore contact) (see para 0507) , and; (c) separating the nanoparticulate biomaterial from the multimodal chromatography resin, whereby the nanoparticulate biomaterial is isolated and/or purified from other components of the sample (product recovery) (see para. 0507) . Regarding Claim 2: Noyes teaches the method of claim 1, wherein the nanoparticulate biomaterial is selected from the group consisting of extracellular vesicles and particles (EVP) (EVs) (see para. 0004) , viruses, viral vectors, pseudoviruses , virus-like particles, polymeric nanoparticles, lipidic nanoparticles, artificial lipid membrane vesicles, and nanoparticulate drug carriers. Regarding Claim 3: Noyes teaches the method of claim 2, wherein the nanoparticulate biomaterial is EVP comprising exomeres , supermeres , exosomes, and/or microvesicles (see para. 0119) . Regarding Claim 4: Noyes teaches the method of claim 1, wherein the nanoparticulate biomaterial has an average particle size in a range from about 50 nm to about 100 nm, or from about 100 nm to about 150 nm, or from about 100 nm to about 200 nm, about 200 nm or less, from about 200 nm to about 1000 nm, or more than 1000 nm (see para. 0119) . The same particles as disclosed by the applicant are separated by the invention of Noyes, therefore they would inherently have the same particle size. Further the ranges given cover all possible particle sizes. Regarding Claim 5: Noyes teaches the method of claim 1, wherein the sample is a biological fluid; plasma; interstitial fluid; cerebrospinal fluid; saliva; cell culture medium (cultured cells) (see para. 0119) ; homogenized biological cells, tissue, or extracellular matrix; a pharmaceutical composition; a vaccine composition; or aerosol droplets or breath condensate; tear fluid; tissue aspirate, sputum; nasal fluid; lavage; artificially prepared emulsion, micelles, lipid droplets, or liposomes; or a tissue homogenate from a mammal, plant, mushroom, or alga. Regarding Claim 6: Noyes teaches the method of claim 1, wherein the multimodal chromatography resin comprises porous resin particles (porous device) (see claim 86) having one or more functional groups (ligands possessing functional groups) selectively disposed inside the porous resin particles (see para. 0247) . Regarding Claim 7: Noyes teaches the method of claim 6, wherein the functional groups are selected from ionic groups, hydrophobic groups (see para. 0247) , hydrophilic groups, amphiphilic groups, polar uncharged groups, non-polar groups, affinity-based groups, octylamine, and N-benzyl, N-methyl ethanolamine. Regarding Claim 16 : Noyes teaches the method of claim 1, wherein the step of contacting is performed using a bed of said multimodal chromatography resin, the bed disposed in a chromatography column (MMC column) (see para. 0208) , and wherein the step of separating is performed by eluting fractions from the column, some of said fractions (selectively eluting the target) comprising the isolated and/or purified nanoparticulate biomaterial (see para. 0202) . Regarding Claim 21: Noyes teaches the method of claim 1, wherein the method does not comprise ultracentrifugation. Method is done in comparison to ultracentrifugation (see para. 0097). Regarding Claim 22: Noyes teaches the method of claim 1, wherein the nanoparticulate biomaterial is separated from other biomaterial present in the sample (see para. 0077, 0085) . Regarding Claim 23: Noyes teaches the method of claim 22, wherein the other biomaterial is protein or other particulate material (protein impurities) (see para. 0085) . Regarding Claim 24: Noyes teaches the method of claim 1, wherein the nanoparticulate biomaterial is fractionated to yield one or more isolated and/or purified subpopulations (sub-fractionation) (see para. 0142, 0222) . Regarding Claim 26: Noyes teaches the method of claim 1, wherein the isolated and/or purified EVP are enriched in CD9, annexin A2, and/or 14-3-3 zeta/delta compared to the sample (see para. 0291) . CD9 is one of the polypeptides comprised by the EV and the EV is purified therefore the CD9 is enriched. Regarding Claim 27: Noyes teaches the method of claim 1, further comprising analyzing the separated nanoparticulate biomaterial using a method selected from TEM, BCA, WB, TRPS, nFCM , or nLC -MS/MS (impurities are measured by BCA assay) (see para. 0074) . Regarding Claim 28: Noyes teaches the chromatography column (MMC column) (see para. 0208) configured for performing the method of claim 1 (see claim mapping for claim 1 above) . 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. Claim(s) 8 -10 is/are rejected under 35 U.S.C. 103 as being unpatentable over Noyes et al (US 2022/0387906) as applied to claim 6 above, and further in view of Jones et al (WO 2019133842) . Regarding Claim 8: Noyes teaches the method of claim 6, wherein the multimodal chromatography resin is capable of separating said nanoparticulate biomaterial from other components of the sample by at least a first mode and a second mode (it is multimodal) , and wherein the second mode is different from size exclusion chromatography (see para. 0247) . Noyes does not teach wherein the first mode is size exclusion chromatography . Jones teaches multimodal chromatography wherein the first mode is size exclusion chromatography (see para. 00 06 ) . Noyes and Jones are analogous inventions in the art of mixed modal chromatography separation of EVs. It would have been obvious to one skilled in the art, before the effective filing date of the invention to add the size exclusion first mode of Jones to the mixed modal resin of Noyes because it allows unbound molecules to be separated by size exclusion (see Jones para. 0007). Further it is the simple addition of a known resin mode to a known chromatography separation process. Obviously resulting in the additional separation of unbound material, with an expectation of success. The combination of familiar elements is likely to be obvious when it does no more than yield predictable results. See KSR International Co. v. Teleflex Inc. , 550 U.S. __,__, 82 USPQ2d 1385, 1395 – 97 (2007) (see MPEP § 2143, A.). Regarding Claim 9: Noyes, as modified, teaches the method of claim 8, wherein the second mode is ion exchange chromatography, hydrophobic interaction chromatography, reversed phase chromatography, or affinity chromatography (see Noyes para. 0249) . Regarding Claim 10: Noyes, as modified, teaches the method of claim 9, wherein the ion exchange chromatography is anion exchange or cation exchange chromatography (see Noyes para. 0249) . Claim(s) 11 , 17 , 19, 20, 25 , and 29-32 is/are rejected under 35 U.S.C. 103 as being unpatentable over Noyes et al (US 2022/0387906) as applied to claim s 1, 6 , 16, 24, and 28 above, and further in view of Lee et al (WO 2021/163696) . Regarding Claim 11: Noyes teaches the method of claim 6 . Noyes does not teach the porous resin particles comprise pores having an average size of about 19 nm, about 50 nm, or about 72 nm. Lee teaches a multi modal (dual modal) chromatography device wherein the porous resin particles comprise pores having an average size of 40 to 70 nm. Given that the prior art range of 40 to 70 nm completely encompasses the claimed value of about 50 nm a prima facie case of obviousness exists and it would have been obvious to one skilled in the art to use a resin particles with pores of about 50 nm (see pg. 10 lines 4-8) . Noyes and Lee are analogous inventions in the art of multimodal resins used for EV isolation. It would have been obvious to one skilled in the art before the effective filing date to use resin particles with an average pore size of about 50 nm as the porous support of Noyes because it is within a range known to be appropriate for isolating EVs (see Lee pg. 10 lines 4-8) which is the same compound being isolated in Noyes. Regarding Claim 17: Noyes teaches the method of claim 16. Noyes does not teach wherein the chromatography column is a sandwich column comprising the bed of said multimodal chromatography resin and a second bed comprising a second chromatography resin, wherein the multimodal chromatography resin and the second chromatography resin are capable of different modes of separation. Noyes further teaches that the column can contain a bed (be packed) of media (see para. 0252). Lee teaches a chromatography column that is a sandwich column comprising the bed of said multimodal chromatography resin (size exclusion media) and a second bed comprising a second chromatography resin (cation exchange media) , wherein the multimodal chromatography resin and the second chromatography resin are capable of different modes of separation (see fig. 2c, pg. 2, lines 6-8). Noyes and Lee are analogous inventions in the art of multimodal resins used for EV isolation. It would have been obvious to one skilled in the art before the effective filing date to arrange the media of Noyes in a sandwich column, as disclosed by Lee it is an arrangement known to be effective for separating EVs (see Lee pg. 1, lines 29-34), which is the same material being isolated in Noyes (see para. 0005). And because it is a simple rearrangement of parts from multiple columns into one column, obviously resulting in separation, with an expectation of success. The mere rearrangement of parts, without any new or unexpected results, is within the ambit of a person of ordinary skill in the art. See In re Japikse , 86 USPQ 70 (CCPA 1950) (see MPEP § 2144.04). Regarding Claim 19: Noyes, as modified, teaches the method of claim 17, wherein the multimodal chromatography resin is disposed above the second chromatography resin in the column (resin in column can be placed in any order) (see Burton pg. 14 lines 3-15) . Regarding Claim 20: Noyes teaches the method of claim 16, wherein the chromatography column compris es the bed (layer) of said multimodal chromatography resin and at least two other columns comprising other chromatography resins, wherein the multimodal chromatography resin and the other chromatography resins are capable of different two or more modes of separation (cation exchange, anions exchange, and mixed mode) (see fig. 1, para. 0026-0031) . Noyes does not teach the column is a multilayer column and the multimodal resin is in layers with the at least two other resin layers. Lee teaches an EV separation column comprising layers of beds of resins (see fig. 2c). Noyes and Lee are analogous inventions in the art of EV separation with chromatography. It would have been obvious to one skilled in the art to layer the resins of Noyes in one column, as disclosed by Lee because it is a simple rearrangement of parts, obviously resulting separation of impurities for the EV solution, with an expectation of success. The mere rearrangement of parts, without any new or unexpected results, is within the ambit of a person of ordinary skill in the art. See In re Japikse , 86 USPQ 70 (CCPA 1950) (see MPEP § 2144.04). Regarding Claim 25: Noyes teaches the method of claim 24, wherein the nanoparticulate biomaterial that is isolated and/or purified is EVP (EV) (see para. 0008) Noyes does not explicitly teach and the other biomaterial is plasma protein, albumin, immunoglobulin, alpha-2 macroglobulin, apolipoprotein B100, apolipoprotein A1, haptoglobin, serotransferrin, and/or alpha-1-antitrypsin . Lee teaches a method of separating EVP (EV) (see pg. 1 lines 24-26 ) wherein the other biomaterial separated is albumin (serum albumin is decreased in the sample) (see pg. 5 lines 32-34). Noyes and Lee are analogous inventions in the art of EV separation with chromatography. It would have been obvious to one skilled in the art to use the method of Noyes to separate EVP from albumin, as disclosed by Lee because through routine experimentation one skilled in the art would have found appropriate EVP containing samples to treat with the known method. Noyes is open to purifying EVP from different samples (see Noyes para. 0077). The use of a known technique to improve similar devices (methods or products) in the same way is likely to be obvious. See KSR International Co. v. Teleflex Inc. , 550 U.S. __,__, 82 USPQ2d 1385, 1395 – 97 (2007) (see MPEP § 2143, C.). Regarding Claim 29: Noyes teaches the chromatography column of claim 28 comprising a multimodal chromatography resin (MMC) (see para. 0246). Noyes does not teach the chromatography column containing a size exclusion chromatography resin, and optionally one or more other chromatography resins, wherein the chromatography column is configured as a sandwich column or a multilayered column. Lee teaches a chromatography column configured as a sandwich column comprising a bed of size exclusion chromatography resin (see fig. 2c, pg. 2, lines 6-8). Noyes and Lee are analogous inventions in the art of multimodal resins used for EV isolation. It would have been obvious to one skilled in the art before the effective filing date to add the size exclusion media of Lee and arrange the media of Noyes in a sandwich column, as disclosed by Lee it is an arrangement known to be effective for separating EVs (see Lee pg. 1, lines 29-34), which is the same material being isolated in Noyes (see para. 0005). And because it is a simple addition of a known chromatography media to a known column, obviously resulting in EV separation with an expectation of success. The combination of familiar elements is likely to be obvious when it does no more than yield predictable results. See KSR International Co. v. Teleflex Inc. , 550 U.S.__,__, 82 USPQ2d 1385, 1395 – 97 (2007) (see MPEP § 2143, A.). Regarding Claim 30: Noyes teaches a multimodal chromatography resin or a column comprising a multimodal chromatography resin (see para. 0247) and instructions for carrying out the method of claim 1 (see claim mapping of claim 1 above). As Noyes teaches the method of claim 1 they teach the instructions of claim 1. Noyes does not teach the kit for isolating and/or purifying a nanoparticulate biomaterial, the kit comprising: the multimodal chromatography resin or a column comprising a multimodal chromatography resin; and the instructions for carrying out the method of claim 1. Lee teaches a kit for isolating and/or purifying a nanoparticulate biomaterial, the kit comprising: the multimodal chromatography resin or a column comprising a multimodal chromatography resin; and the instructions for carrying out the metho d (see pg. 19 lines 17-26) . Noyes and Lee are analogous inventions in the art of EV isolation with multimodal chromatography. It would have been obvious to one skilled in the art to combine the multimodal chromatography resin and instructions for carrying out the method of claim 1, as disclosed by Noyes into a kit, as disclosed by Lee because it is known in the art to package chromatography columns as kits (see Lee pg. 19 lines 17-26) and the elements of Noyes could be combined obviously resulting in a kit that could be used for EV separation with an expectation of success. The combination of familiar elements is likely to be obvious when it does no more than yield predictable results. See KSR International Co. v. Teleflex Inc. , 550 U.S. __,__, 82 USPQ2d 1385, 1395 – 97 (2007) (see MPEP § 2143, A.). The use of a known technique to improve similar devices (methods or products) in the same way is likely to be obvious. See KSR International Co. v. Teleflex Inc. , 550 U.S. __,__, 82 USPQ2d 1385, 1395 – 97 (2007) (see MPEP § 2143, C.). Regarding Claim 31: Noyes teaches the method comprising the steps of:(a) providing a sample (see para. 0008) and a chromatography column comprising a multimodal chromatography resin (see para. 0252) , and optionally one or more other chromatography resins; (b) performing the method of claim 1 (see claim mapping of claim 1 above) , whereby an isolated and/or purified nanoparticulate biomaterial is obtained; and (c) analyzing the isolated and/or purified nanoparticulate biomaterial (nanoparticle tracking analysis) (see para. 0512) . Noyes does not teach a method of diagnosing a disease or medical condition that the sample is provided from a subject suspected of having the disease or medical conditio n, providing a size exclusion chromatography resin wherein the chromatography column is configured as a sandwich column or a multilayered column analyzing and analyzing the isolated and/or purified nanoparticulate biomaterial to diagnose the disease or medical condition . No y es further teaches that EVs can be used to diagnose diseases (see para. 0004) . Lee teaches a method of diagnosing a disease or medical condition that the sample is provided from a subject suspected of having the disease or medical conditio n (identifying a subject having a disease) (see pg. 19 lines 10-15), providing a size exclusion chromatography resin wherein the chromatography column is configured as a sandwich column or a multilayered column (see fig. 2c, pg. 2, lines 6-8) and analyzing the isolated and/or purified nanoparticulate biomaterial to diagnose the disease or medical condition (blood based analytical method) (see pg. 7 lines 24-28). Noyes and Lee are analogous inventions in the art of EV isolation with multimodal chromatography. It would have been obvious to one skilled in the art before the effective filing date to add the size exclusion media of Lee and arrange the media of Noyes in a sandwich column, as disclosed by Lee it is an arrangement known to be effective for separating EVs (see Lee pg. 1, lines 29-34), which is the same material being isolated in Noyes (see para. 0005). And because it is a simple addition of a known chromatography media to a known column, obviously resulting in EV separation with an expectation of success. The combination of familiar elements is likely to be obvious when it does no more than yield predictable results. See KSR International Co. v. Teleflex Inc. , 550 U.S.__,__, 82 USPQ2d 1385, 1395 – 97 (2007) (see MPEP § 2143, A.). It would have further been obvious to use the method of Noyes on sample from a subject suspected of having a disease and diagnose the disease of medical condition, as disclosed by Lee because through routine experimentation one skilled in the art would have found appropriate uses for the known method of Noyes and Noyes teaches that EVs are known biomarkers for disease (see Noyes para. 0004). The use of a known technique to improve similar devices (methods or products) in the same way is likely to be obvious. See KSR International Co. v. Teleflex Inc. , 550 U.S. __,__, 82 USPQ2d 1385, 1395 – 97 (2007) (see MPEP § 2143, C.). Regarding Claim 32: Noyes, as modifies, teaches the method of claim 31, further comprising:(d) treating the disease or medical condition (selecting a treatment…determining a course of treatment) (see Lee pg. 19 lines 10-15) . Claim(s) 12 , 13, and 15 is/are rejected under 35 U.S.C. 103 as being unpatentable over Noyes et al (US 2022/0387906) as applied to claim 6 above, and further in view of Burton et al (USPN 5,652,348) . Regarding Claim 12: Noyes teaches the method of claim 1. Noyes further teaches the step of contacting can be performed with a suspension (the resin can be formed in a suspension) (see para. 0252). Noyes does not the suspension of particles of said multimodal chromatography resin in an aqueous medium. Burton teaches that the suspension of the multimodal chromatography resin is in an aqueous medium ( suspended in a stirred batch system when the resin is mixed with the aqueous medium ) (see col. 14 lines 4-9) . Noyes and Burton are analogous inventions in the art of separations with mixed modal chromatography resins. It would have been obvious to one skilled in the art to replace the unspecified liquid in the suspension of Noyes with an aqueous medium, as disclosed by Burton because it is a suspension medium known to be appropriate for the separation of biological materials containing proteins (see Burton col. 4 lines 21-24) which is the same type of material being separated in Noyes (see Noyes para. 0004) and through routine experimentation one skilled in the art would have found an appropriate medium for the suspension. Regarding Claim 1 3 : Noyes, as modified, teaches method of claim 12 . Burton further teaches wherein the suspension is mixed during the incubation period (stirred batch) (see Burton col. 14 lines 4-9) . It would have been obvious to one skilled in the art to mix the suspension of Noyes during the incubation period, as disclosed by Burton because it provides to proper conditions for compounds to bind to the resin (see Burton col. 14 lines 4-11), and binding to the resin is desirable in Noyes. Regarding Claim 15: Noyes, as modified, teaches the method of claim 12, wherein the step of separating includes centrifugation or filtration (ultrafiltration (UF)) (see Noyes para. 0067) of the suspension and harvesting the isolated and/or purified nanoparticulate biomaterial from the supernatant or filtrate (see Noyes para. 0072) . Claim (s) 14 is/are rejected under 35 U.S.C. 103 as being unpatentable over Noyes et al (US 2022/0387906) . Regarding Claim 14: Noyes teaches the method of claim 1. Noyes does not explicitly teach the incubation period is long enough to attain binding equilibrium of undesired components of the sample with the functional groups inside the porous resin particles of the multimodal chromatography resin. Noyes further teaches that the incubation period (residence time) can be altered to change the desorption of the impurities (undesired components) (see para. 0199). As incubation period is a known result effective variable It would have been obvious to one skilled in the art to adjust the incubation period, as disclosed by Noyes in order to optimize the binding of impurities and thereby attain binding equilibrium. “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” See In re Aller , 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). The discovery of an optimum value of a known result effective variable, without producing any new or unexpected results, is within the ambit of a person of ordinary skill in the art. See In re Boesch , 205 USPQ 215 (CCPA 1980) (see MPEP § 2144.05, II.). Claim(s) 18 is/are rejected under 35 U.S.C. 103 as being unpatentable over Noyes et al (US 2022/0387906) and Lee et al ( WO 2021/163696 ) as applied to claim 17 above, and further in view of Jones et al (WO 2019 / 133842) . Regarding Claim 18: Noyes, as modified teaches the method of claim 17. Noyes does not teach the multimodal chromatography resin performs size exclusion and anion exchange and the second chromatography resin performs size exclusion. Noyes further teaches that the multimodal chromatography resin performs anion exchange (see Noyes para. 0249) and Burton further teaches that the second resin performs size exclusion (see Burton pg. 2, lines 6-8). Jones teaches a mixed modal resin that performs size exclusion and has a functional ligand (see para. 0019 ). Noyes and Jones are analogous inventions in the art of mixed modal chromatography separation of EVs. It would have been obvious to one skilled in the art, before the effective filing date of the invention to add the size exclusion first mode of Jones to the mixed modal resin of Noyes because it allows unbound molecules to be separated by size exclusion (see Jones para. 0007). Further it is the simple addition of a known resin mode to a known chromatography separation process. Obviously resulting in the additional separation of unbound material, with an expectation of success. The combination of familiar elements is likely to be obvious when it does no more than yield predictable results. See KSR International Co. v. Teleflex Inc. , 550 U.S. __,__, 82 USPQ2d 1385, 1395 – 97 (2007) (see MPEP § 2143, A.). Conclusion Any inquiry concerning this communication or earlier communications from the examiner should be directed to FILLIN "Examiner name" \* MERGEFORMAT CLAIRE A NORRIS whose telephone number is FILLIN "Phone number" \* MERGEFORMAT (571)272-5133 . The examiner can normally be reached FILLIN "Work Schedule?" \* MERGEFORMAT M-Th 7:30-5 F: 8-12 . Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice. If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, FILLIN "SPE Name?" \* MERGEFORMAT Ramdhanie Bobby can be reached at FILLIN "SPE Phone?" \* MERGEFORMAT 571-270-3240 . The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300. Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000. /CLAIRE A NORRIS/ Primary Examiner, Art Unit 1779 3/26/2026