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 .
Status of the Claims
Claims 1-16 were pending. Claims 2 and 4 are cancelled.
Claims 1, 3, and 5-16 are examined herein.
Claim Objections
Claims 11 and 15 are objected to because of the following informalities:
Claim 11 contains a copy of claim 12.
Claim 15 recites (1) when the polymer is the polysaccharide, the enzyme capable of degrading the polymer is a sugar degrading enzyme, and (3) when the polymer is the protein, the enzyme for degrading the polymer is a proteolytic enzyme. Should be (1) when the polymer is the polysaccharide, the enzyme capable of degrading the polymer is a sugar degrading enzyme, and (2) when the polymer is the protein, the enzyme for degrading the polymer is a proteolytic enzyme.
Appropriate correction is required.
Withdrawn Rejections
The objection to claim 1 is withdrawn in view of claim amendments.
The rejection of claims 1, 3, 9, 10, and 12-14 under 35 U.S.C. § 102(a)(1) is withdrawn in view of claim 1 amendments. However, upon further consideration, a new ground(s) of rejection is made under 35 U.S.C. § 103 in view of previously presented prior art of Kitchen et al. (WO 2019236853).
The rejection of claims 2 and 4 is withdrawn in view of claims cancellation.
The rejection of claims 15-16 under 35 U.S.C. § 103 is withdrawn in view of claim 16 amendments. However, upon further consideration, a new ground(s) of rejection is made under 35 U.S.C. § 103 in view Ohta, Kitchen, Hoffman (PGPub 20200392219), Berenson et al. (PGPub 20200392219), and as evidenced by Vlassov et al. (US Pat. 8901284).
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION. —The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1-14 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 1 recites (ii) particles and (i') particles. It is unclear if the claim refers to the same kind or different kinds of particles. The claim is interpreted as referring to the same particles in both (ii) and (i'). Claims 2-14 are rejected because they depend from rejected claim 1.
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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
Determining the scope and contents of the prior art.
Ascertaining the differences between the prior art and the claims at issue.
Resolving the level of ordinary skill in the pertinent art.
Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1, 3, 7, 9-10, and 12-14 are rejected under 35 U.S.C. 102(a)(1) as being unpatentable over Ohta et al. (IDS; PGPub 20150010913), Klass et al. (PGPub 20150024961), and Kitchen et al. (WO 2019236853), and as evidenced by CD9-Wikipedia (2025) and Bovine serum albumin-Wikipedia (2025).
Regarding claim 1, Ohta teaches a method for capturing an extracellular vesicle ([0070]) comprising contacting a monoclonal antibody with an exosome and isolating the reacted exosome using streptavidin-immobilized magnetic beads ([0071]). Exosome is another term for the extracellular vesicle of instant invention. The streptavidin-immobilized magnetic beads are the particles of instant invention. The monoclonal antibody is a monoclonal antibody against CD9, CD63 or CD81 proteins located on exosomes (0010]). The monoclonal antibody is the substance having the affinity to the extracellular vesicle membrane of instant invention. Ohta teaches the monoclonal antibody for detecting or capturing an exosome in a biological sample ([0009]), and the particles are magnetic beads with immobilized anti-CD9 antibody ([0146], col. 2). Capturing exosomes in a biological sample taught by Ohta is the same as separating the particles bound to the extracellular vesicles via the substance from the mixture the immobilized substance of instant invention.
Ohta does not specifically teach treating the mixture by ultrasonication or with an enzyme capable of degrading the polymer, and wherein the polymer is a polysaccharide, a protein or a polyvinyl derivative having a carbonyl-containing hydrophilic group.
Regarding claim 1, Klass teaches methods of using biomarkers (Title), wherein the biomarkers are exosomes (Abstract). Klass also teaches ultrasonication of exosomes. Specifically, that ultrasonication can enhance recovery of exosomes from biological samples by increasing release of exosomes from a tissue sample ([0127]).
Ohta and Klass do not specifically teach wherein the polymer is a polysaccharide, a protein or a polyvinyl derivative having a carbonyl-containing hydrophilic group.
Regarding claim 1, Kitchen teaches methods for detecting and treating bladder cancer in a subject using the gene expression level measurements from exosomes (Abstract). Kitchen also teaches purification of extracellular vesicles using polysaccharide polymers.
Specifically, Kitchen teaches isolation methods for exosomes using volume-excluding polymers such as polyethylene glycol, dextran, dextran sulfate, dextran acetate, polyvinyl alcohol, polyvinyl acetate, or polyvinyl sulfate ([00294]). Dextran is a polysaccharide.
It would have been obvious to one having ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of Ohta by employing ultrasonication as taught by Klass, in order to enhance recovery of exosomes from biological samples (Klass, [0127]), as an obvious matter of using of known technique (ultrasonication) to improve similar method (recovery of exosomes) in the same way.
One having ordinary skill in the art would have had a reasonable expectation of success because Ohta is generic on using additional sample treatment methods and Klass demonstrates that ultrasonication can enhance recovery of exosomes from samples when applied prior to exposure of the exosomes to binding agents ([0127]).
It would have been obvious to one having ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of Ohta by employing polysaccharide polymers as taught by Kitchen ([00294]), in order to isolate exosomes, as an obvious matter of simple substitution of one known element (BSA of Ohta) for another (polysaccharide of Kitchen) to obtain predictable results.
One skilled in the art would have a reasonable expectation of success in substituting BSA polymer of Ohta with polysaccharide polymers of Kitchen, because Kitchen specifically teaches using polysaccharide polymers for isolation of exosomes. Both BSA and polysaccharide dextran are large polymers known for their similar volume-excluding properties.
Regarding claim 3, Ohta teaches the target particles are separated from the mixture solution – “the beads were washed with PBS using a magnet, and the evaluation of the amount of CD9 on the exosomes captured in the supernatant was carried out by WB” (Ohta, [0146], col. 2). WB is western blot analysis method of proteins that inherently requires release of the exosomes from the target particles after separating the target particles, thus meeting the limitations of claim 3 reciting releasing the extracellular vesicle.
Regarding claim 7, Ohta in view of Klass and Kitchen teach isolation methods for exosomes using volume-excluding polymers such as polyethylene glycol, dextran, dextran sulfate, dextran acetate, polyvinyl alcohol, polyvinyl acetate, or polyvinyl sulfate (Kitchen, [00294]). Dextran is a polysaccharide, meeting the limitation of claim 7 reciting the polymer is a polysaccharide.
Regarding claims 9-10, Ohta as evidenced by Bovine serum albumin-Wikipedia teaches using 1% BSA dissolved in PBS solution as a medium for interaction between anti-CD9 antibody and exosomes from sera (Ohta, [0146], col. 2). BSA is the polymer of instant invention and also a protein. Molecular weight of BSA is 66 kDa, meeting the limitation of claim 9 reciting average molecular weight of 10 kDa or more (Bovine serum albumin – Wikipedia; section “Properties”). BSA was dissolved at 1% concentration, meeting the limitation of claim 10 reciting the polymer concentration is 0.01-10% by weight.
Regarding claim 12, Ohta as evidenced by CD9-Wikipedia teaches that anti-CD9 antibody taught by Ohta ([0146], col. 2) targets CD9 protein, which is a member of the tetraspanin family (CD9-Wikipedia, lines 1-2), meeting the limitation of claim 12 reciting the substance having the affinity to the extracellular vesicle membrane is an antibody against a tetraspanin membrane protein.
Regarding claim 13, Ohta teaches “exosomes prepared from a culture supernatant of COST cells” (Ohta, [0144]) meeting the limitation of claim 13 reciting the extracellular vesicle-containing sample is a fluid sample from a culture supernatant sample.
Regarding claim 14, Ohta teaches target particles are separated from the mixture solution – “the beads were washed with PBS using a magnet, and the evaluation of the amount of CD9 on the exosomes captured in the supernatant was carried out by WB” (Ohta, [0146], col. 2). Evaluation of the amount of CD9 on the exosomes meets the limitation of claim 14 reciting analyzing the separated extracellular vesicle because the evaluation of the amount of CD9 on the exosomes is a method of extracellular vesicle protein analysis.
Claims 5 and 6 are rejected under 35 U.S.C. 103 as being unpatentable over Ohta in view of Klass and Kitchen, as applied to claim 1 above and further in view of Amazon (Branson CPX-952-116R Ultrasonic Bath, 2013).
The teachings of Ohta in view of Klass and Kitchen have been set forth above.
Ohta in view of Klass and Kitchen do not specifically teach a water bath ultrasonication and a frequency of the ultrasonication is in a range of 40 kHz or less or 950 kHz or more.
Regarding claims 5 and 6, Amazon provides evidence of a water bath ultrasonication. Ultrasonic baths used in biological experiments are water baths as evidenced by Amazon in the title “Branson CPX-952-116R Series M Mechanical Cleaning Bath with Mechanical Timer, 0.5 Gallons”, wherein 0.5 Gallons refers to volume of water required for proper function of the ultrasonic bath.
It would have been obvious to one having ordinary skill in the art before the effective filing date of the claimed invention to choose wet ultrasonication because this is how ultrasonication is routinely performed in lab experiments and wet ultrasonic baths are widely available as evidenced by Amazon.
One skilled in the art would have a reasonable expectation of success of using wet ultrasonication because this is how ultrasonication experiments are routinely performed in the labs.
Regarding claim 6, Amazon provides evidence that ultrasonic bath, model Branson CPX-952-116R, has a transducer working at 40 kHz frequency (Amazon, pg. 1, section “About this item”), falling within the range and therefore meeting the limitation of claim 5, which recites a range of 40 kHz or less. Amazon also provides evidence that the bath was first available for sale on July 10, 2013 (pg. 2, section “Product details”) before the effective filing date of the claimed invention.
Claim 8 is rejected under 35 U.S.C. 103 as being unpatentable over Ohta in view of Klass and Kitchen, as applied to claim 7 above and in further in view of Mir (PGPub 20200056229).
The teachings of Ohta in view of Klass and Kitchen have been set forth above.
Ohta in view of Klass and Kitchen do not specifically teach the polysaccharide is a cellulose derivative in which a hydrogen atom of at least one hydroxy group in a cellulose is substituted with a carboxyalkyl or hydroxyalkyl.
Regarding claim 8, Mir teaches sequencing polymers (Abstract) and an effect of volume excluding polymers on speed of binding between oligos ([0931]). Mir also teaches cellulose derivatives in which a hydrogen atom of at least one hydroxy group in a cellulose is substituted with a carboxyalkyl or hydroxyalkyl.
Specifically, Mir teaches that the speed of binding between oligos can be increased by volume excluding agents selected from the group consisting of hydroxypropyl methyl cellulose, hydroxyethyl methyl cellulose, hydroxybutyl methyl cellulose, hydroxypropyl cellulose, and hydroxyl methylcellulose ([0931]), meeting the limitation of claim 8 reciting hydroxyalkyl substituted cellulose.
It would have been obvious to one having ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of Ohta, Klass and Kitchen by employing volume excluding agents as taught by Mir ([0931]), in order to isolate exosomes, as an obvious matter of simple substitution of one known element (dextran polysaccharide of Kitchen, [00294]) for another (hydroxyalkyl substituted cellulose of Mir) to obtain predictable results.
One skilled in the art would have a reasonable expectation of success in substituting volume excluding polymers of Kitchen with volume excluding polymers of Mir, because both groups of polymers have a similar mode of action (promoting association of molecules by volume excluding action) and oligos taught by Mir are well-known in the art as substances having affinity to other molecules – aptamers.
Claim 11 is rejected under 35 U.S.C. 103 as being unpatentable over Ohta in view of Klass and Kitchen, as applied to claim 1 above, in view of Inuzuka et al. (IDS; PGPub 20200041391).
The teachings of Ohta in view of Klass and Kitchen have been set forth above.
Ohta in view of Klass and Kitchen do not specifically teach the method of claim 1 further comprises mixing a chelating agent.
Regarding claim 11, Inuzuka teaches methods for recovering extracellular vesicles (Title). Inuzuka also teaches treating an extracellular vesicle-containing sample with a chelating agent.
Specifically, Inuzuka teaches a method of recovering an extracellular vesicle(s), comprising: (1) treating an extracellular vesicle-containing sample with a chelating agent; and (2) separating the extracellular vesicle(s) from the extracellular vesicle-containing sample treated with the chelating agent ([0008]).
It would have been obvious to one having ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of Ohta, Klass and Kitchen by employing a chelating agent as taught by Inuzuka ([0008]), in order to isolate exosomes. One having ordinary skill in the art would have been motivated to make such a change because Inuzuka teaches that purification of extracellular vesicles using immunoprecipitation method using an antibody against an extracellular vesicle marker “does not always have high purity for recovered extracellular vesicles” ([0005]) and the treatment with chelating agents is “able to recover the extracellular vesicles that are more homogeneous in quality” ([0006]). The use of chelating agents would have been desirable to those of ordinary skill in the art the reasons mentioned above.
One skilled in the art would have a reasonable expectation of success in combining the method of Ohta with chelating agents of Inuzuka, because Inuzuka teaches successful use of chelating agents for isolation of exosomes.
Claims 15 and 16 are rejected under 35 U.S.C. 103 as being unpatentable over Ohta in view of Kitchen, Hoffman (PGPub 20200392219), Berenson et al. (PGPub 20200392219), and as evidenced by Vlassov et al. (US Pat. 8901284).
Regarding claims 15 and 16, Ohta teaches a method for capturing an extracellular vesicle ([0070]) comprising contacting a monoclonal antibody with an exosome and isolating the reacted exosome using streptavidin-immobilized magnetic beads ([0071]). Exosome is another term for the extracellular vesicle of instant invention. The streptavidin-immobilized magnetic beads are the particles of instant invention. The monoclonal antibody is a monoclonal antibody against CD9, CD63 or CD81 proteins located on exosomes (0010]). The monoclonal antibody is the substance having the affinity to the extracellular vesicle membrane of instant invention. Ohta teaches the monoclonal antibody for detecting or capturing an exosome in a biological sample ([0009]), which is a substance having an affinity to extracellular vesicle membrane.
Additionally, Ohta teaches “a kit containing the set of monoclonal antibodies of the present invention, and the above-mentioned kit can be used so long as the kit is used for a detection method using the set of the monoclonal antibodies of the present invention when detecting exosomes in a sample” ([0091]).
Kitchen teaches the use of volume-excluding polymer selected from the group consisting of polyethylene glycol, dextran, dextran sulfate, dextran acetate, polyvinyl alcohol, polyvinyl acetate, or polyvinyl sulfate ([0294]). Dextran is a polysaccharide polymer.
Vlassov teaches methods, compositions, and kits for the isolation of exosomes from biological fluids and tissues (Abstract). Vlassov also provides evidence of the benefit of using the volume-excluding polymers of Kitchen as “volume-excluding polymers are capable of differentially precipitating exosomes thereby allowing exosome isolation by low-speed (benchtop) centrifugation or filtration” (Col. 2, lines 17-19).
Ohta, Kitchen, and Vlassov do not specifically teach a kit comprising: a polymer that is a polysaccharide; a substance having an affinity to extracellular vesicle membrane; and an enzyme for degrading the polymer, wherein the substance is in a free form or in a form immobilized on particles, and the kit further comprises particles when the substance is in a free form, and the enzyme for degrading the polymer is a sugar degrading enzyme.
Regarding claims 15-16, Hoffman teaches compositions and methods of use with extracellular vesicles comprising membrane-tethered tgf-beta (Abstract). Hoffman also teaches an enzyme for degrading a polysaccharide polymer.
Specifically, Hoffman teaches that extracellular vesicles are covered with hyaluronic acid/proteoglycan complexes and pre-treatment of such EV with hyaluronidase completely removes those complexes, reducing aggregation and doubling the number of single EV which were available for analysis or treatment ([0249]).
Ohta, Kitchen, Vlassov, and Hoffman do not specifically teach a polysaccharide polymer is hyaluronic acid that can be degraded by hyaluronidase.
Regarding claims 15-16, Berenson teaches methods for activating and expanding cells. Berenson also teaches a polysaccharide polymer that is hyaluronic acid.
Specifically, Berenson teaches biocompatible surfaces for ligand immobilization, the surface may be a polymer comprising polysaccharides and a polysaccharide may include hyaluronic acid ([0140]-[0141]). Berenson does not specifically teach hyaluronic acid is a volume-excluding polymer, but this is an inherent property of large hydrophilic polymers, such as hyaluronic acid in aqueous solutions.
It would have been obvious to one having ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of Ohta by adding a volume-excluding polymer as taught by Kitchen and Vlassov, in order to allowing exosome isolation by low-speed centrifugation or filtration” (Kitchen, Col. 2, lines 17-19), as an obvious matter of simplifying exosome isolation. One having ordinary skill in the art would have been motivated to make such a change because low-speed centrifugation or filtration are more affordable methods than high-speed centrifugation normally required for exosome isolation. The use of a volume-excluding polymer would have been desirable to those of ordinary skill in the art the reasons mentioned above.
One skilled in the art would have a reasonable expectation of success of combining the prior art references of Ohta, Kitchen, and Vlassov because both references are similarly drawn to exosomes, and Kitchen has demonstrated successful use of volume-excluding polysaccharide polymers for exosome isolation.
It would have been obvious to one having ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of Ohta, Kitchen, and Vlassov by employing hyaluronic acid as a biocompatible polymer as taught by Berenson (Abstract), in order to allow exosome isolation using volume-excluding properties of hyaluronic acid, as an obvious matter of simple substitution of one known element (polysaccharide polymer of hyaluronic acid of Berenson) for another (polysaccharide polymer of dextran of Kitchen) to obtain predictable results.
One skilled in the art would have a reasonable expectation of success of combining the prior art references because both polysaccharide polymers dextran and hyaluronic acid are known for their biocompatibility, and both are polymers with volume-excluding properties.
It would have been obvious to one having ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of Ohta, Kitchen, Vlassov, and Berenson by employing hyaluronidase to degrade hyaluronic acid attached to extracellular vesicles as taught by Hoffman, in order to make isolation extracellular vesicles more reproducible and resulting in high quality preparations of EV (Hoffman, [0249]). as an obvious matter of purifying extracellular vesicles of better quality. One having ordinary skill in the art would have been motivated to make such a change to purify extracellular vesicles of better quality. The use of hyaluronic acid would have been desirable to those of ordinary skill in the art for the reasons mentioned above. The use of hyaluronidase has an additional benefit of degrading hyaluronic acid polymer after exosome purification in order to reduce viscosity of the final exosome preparation.
One skilled in the art would have a reasonable expectation of success of combining the prior art references because all prior art references are similarly drawn to extracellular vesicles, and Hoffman makes isolation of extracellular vesicles more reproducible using hyaluronidase.
It would have been obvious to one having ordinary skill in the art before the effective filing date of the claimed invention to have modified the kit of Ohta by adding hyaluronic acid of Berenson and hyaluronidase of Hoffman, in order to have all essential method reagents assembled in the kit. One having ordinary skill in the art would have been motivated to make such a change because the kit format saves money and resources by reducing waste. The kit format would have been desirable to those of ordinary skill in the art the reasons mentioned above.
One skilled in the art would have a reasonable expectation of success of combining all compositions in the kit because kits are known in the art as a form of reagent organization.
Response to Arguments
Applicant's arguments filed February 17, 2026 have been fully considered.
Applicant argues about the rejections of claim 2 under 35 U.S.C. § 112(a) (Section B. pg. 6-12) and under 35 U.S.C. § 112(b) (pg. 13, par. 1-2). Since Applicant cancelled claim 2, the argument is moot and the rejections of claim 2 are withdrawn.
Applicant argues that since amended claim 1 incorporates the features of claim 4, which was not rejected under 35 U.S.C. § 102(a)(l), the rejection of claims 1, 3, 9, 10, and 12-14 is moot and should be withdrawn. The argument is persuasive and the rejection of claims 1, 3, 9, 10, and 12-14 under 35 U.S.C. § 102(a)(1) is withdrawn in view of claim 1 amendments. However, upon further consideration, a new ground(s) of rejection is made under 35 U.S.C. § 103 in view of previously presented prior art of Kitchen (see details above). Briefly, Kitchen teaches purification of extracellular vesicles using polysaccharide polymers.
Applicant argues about claims 2 and 4-6 rejected under 35 U.S.C. § 103 as being unpatentable over Ohta in view of Klass as evidenced by Amazon (pg. 13, last par. – pg. 17).
Specifically, Applicant argues that “A person of ordinary skill in the art would not have has a reason to combine Ohta with Klass because Ohta which teaches use of PBS solution containing 1 % BSA (i.e., use of highly abundant albumin) with Klass ([0125]-[0127]) teaches against using albumin (highly abundant serum proteins) in the isolation of EVs. These disparate teachings would have instead informed a person of ordinary skill in the art that these references should not be combined and that the methods disclosed in each are not compatible” (pg. 15, par. 4).
The argument is not persuasive because neither Ohta nor Klass teach away from the combination of Ohta’s method for capturing an extracellular vesicle ([0070]) comprising contacting a monoclonal antibody with an exosome and isolating the reacted exosome using streptavidin-immobilized magnetic beads with the teaching of Klass that ultrasonication can enhance recovery of exosomes from biological samples by increasing release of exosomes from a tissue sample ([0127]).
This argument lacks of strength as indicated by Applicant in “Highly abundant proteins, such as albumin and immunoglobulin, may hinder isolation of exosomes from a biological sample” (pg. 14, last par.). The key term here is may hinder. The modal verb “may” is used to indicate possibility or probability (https://www.merriam-webster.com/dictionary/may), but it is not used to indicate any degree of certainty, definitiveness, or inevitability.
MPEP 1504.03.III states that “A reference may be said to teach away when a person of ordinary skill, upon reading the reference...would be led in a direction divergent from the path that was taken by the applicant." See In re Haruna, 249 F.3d 1327, 58 USPQ2d 1517 (Fed. Cir. 2001). “Would be led” requires a stronger argument than “may hinder” relied upon by Applicant.
Additionally, Applicant’s recitation from Klass that “exosomes may be isolated from a biological sample using a system that utilizes multiple antibodies that are specific to the most abundant proteins found in blood. Such a system can remove up to several proteins at once, thus unveiling the lower abundance species such as cell-of-origin specific exosomes” (pg. 14, last par.) by itself provides a solution to an apparent contradiction between Ohta and Klass seen by Applicant.
Klass cautions that albumin and immunoglobulin may hinder isolation of exosomes from a biological sample, and then provides a solution to overcome this effect as “exosomes may be isolated from a biological sample using a system that utilizes multiple antibodies that are specific to the most abundant proteins found in blood. Such a system can remove up to several proteins at once, thus unveiling the lower abundance species such as cell-of-origin specific exosomes” (pg. 14, last par.). As such, there is no contradiction between the teachings of Ohta and Klass, and there is no evidence that the methods disclosed in each are not compatible.
The teaching of Klass that ultrasonication is a solution to overcome potential negative effect of BSA on exosomes isolation answers Applicant’s argument that “The contrary teachings of Ohta and Klass would also not have provided a basis for reasonably expecting success. These rejections are also improper for this additional reason” (pg. 16, par. 3-5). The reason why non-final OA (mailed November 17, 2025) did not explicitly provide a basis for reasonably expecting success of combining Ohta’s BSA with Klass’s ultrasonication is because Ohta’s BSA was not considered as a proper teaching away (see two paragraphs above for more details).
The non-final OA provided the following reasonings to answer more Applicant’s arguments about lack of motivation and lack of reasonable expectation of success presented on pg. 16-17): It would have been obvious to one having ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of Ohta by employing ultrasonication as taught by Klass, in order to enhance recovery of exosomes from biological samples, as an obvious matter of using of known technique to improve similar method in the same way. (OA, pg. 9, last par. – pg. 10, par. 1) and One having ordinary skill in the art would have had a reasonable expectation of success because Ohta is generic on using additional sample treatment methods and Klass demonstrates that ultrasonication can enhance recovery of exosomes from samples when applied prior to exposure of the exosomes to binding agents ([0130]) (OA, pg. 10, par. 3).
Finally, claims 2 and 4 are cancelled and claims 5 and 6 are rejected under 35 U.S.C. § 103 as being unpatentable over Ohta in view of Klass and Kitchen, and further in view of Amazon (see above for details).
Applicant argues that “Ohta and Klass do not teach or suggest a correlation between viscosity reduction and improved EVs recovery rate where reducing viscosity of a mixture …” (pg. 15, last par. – pg. 16, par. 1). The argument is moot because claim 2 reciting viscosity reduction is cancelled.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the date of this final action.
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/ALEXANDER ALEXANDROVIC VOLKOV/Examiner, Art Unit 1677
/BAO-THUY L NGUYEN/Supervisory Patent Examiner, Art Unit 1677 April 4, 2026