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 .
DETAILED OFFICE ACTION
This Office Action is in response to the papers filed on 26 May 2026.
CLAIMS UNDER EXAMINATION
Claims 1-5, 7-8, 10-17 and 21-23 have been examined on their merits.
PRIORITY
EP16173465.2, filed on 08 June 2016, is acknowledged.
WITHDRAWN REJECTIONS
The previous rejections have been withdrawn due to claim amendment.
REJECTIONS
New grounds of rejection have been necessitated by claim amendment.
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 1-5, 7-8, 10-17 and 21-23 are rejected under 35 U.S.C. 101 because the claimed invention is not directed to patent eligible subject matter.
Based on the claims as a whole, claims 1-5, 7-8, 10-17 and 21 are determined to be directed to a law of nature/natural principle. The rationale for the determination is explained below.
Claim 1 is directed to a method processing human platelets.
Question 1: Is the claim to a process, machine manufacture or composition of matter? Yes, the invention recited in claim 1 is a process.
Question 2A Prong 1: Is the claim directed to a law of nature, a natural phenomenon, or an abstract idea (judicially recognized exceptions)? Yes, claim 1 is directed to a law of nature.
(a) The limitations in the claim that set forth the law of nature are:
The 2019 PEG explains that the abstract idea exception includes the following groupings of subject matter:
Mathematical concepts – mathematical relationships, mathematical formulas or equations, mathematical calculations;
Certain methods of organizing human activity – fundamental economic principles or practices (including hedging, insurance, mitigating risk); commercial or legal interactions (including agreements in the form of contracts; legal obligations; advertising, marketing or sales activities or behaviors; business relations); managing personal behavior or relationships or interactions between people (including social activities, teaching, and following rules or instructions); and
Mental processes – concepts performed in the human mind (including an observation, evaluation, judgment, opinion).
Step d recites “selecting” an enriched fraction of human platelet derived extracellular vesicles if the enriched fraction exhibits the in vitro effect. The specification does not recite a definition for the term “selecting”. Therefore, visually identifying extracellular vesicles is interpreted to read on the claim limitation. Such mental observations and evaluations fall within the “mental processes” grouping of abstract idea set forth in the 2019 PEG. 2019 PEG Section I, 84 Fed. Reg. at 52. observations and evaluations that can be performed in the human mind (hence within the “mental processes” grouping of abstract ideas).
Question 2A Prong 2: Does the claim recite additional elements that integrate the judicial exception into a practical application? No.
Claim 1 recites incubating pooled donor-donated platelets at the claimed temperature; providing a lysate and removal of particles. These are considered insignificant extra-solution activities that are required to make the selection required in step d. Claim 1 recites determining an in vitro effect of the enriched fraction. Because the determination does not require a specific assay, it does not integrate the judicial exception. The determining step is an insignificant extra-solution activity that is required in order to make the selection recited in step d. The claim also recites “to obtain a preparation comprising an enriched and selected fraction…”. This is interpreted to be an intended use of the fraction. It does not add significantly more to the recited judicial exceptions.
Question 2B: Do the claims recite any additional elements? Yes.
With respect to Step 2B, limitations that were found to be enough to qualify as “significantly more” when recited in a claim with a judicial exception include:
Improvements to another technology or technical field.
Improvements to the functioning of the computer itself.
Applying the judicial exception with, or by use of, a particular machine.
Effecting a transformation or reduction of a particular article to a different state or thing
Adding a specific limitation other than what is well-understood, routine and conventional in the field, or adding unconventional steps that confine the claim to a particular useful application.
Other meaningful limitations beyond generally linking the use of the judicial exception to a particular technological environment.
With respect to Step 2B, limitations that were found not to be enough to qualify as “significantly more” when recited in a claim with a judicial exception include:
Adding the words ‘‘apply it’’(or an equivalent) with the judicial exception, or mere instructions to implement an abstract idea on a computer
Simply appending well-understood, routine and conventional activities previously known to the industry, specified at a high level of generality, to the judicial exception, e.g., a claim to an abstract idea requiring no more than a generic computer to perform generic computer functions that are well understood, routine and conventional activities previously known to the industry
Adding insignificant extrasolution activity to the judicial exception, e.g., mere data gathering in conjunction with a law of nature or abstract idea
Generally linking the use of the judicial exception to a particular technological environment or field of use.
Do the additional elements result in the claim amounting to significantly more?
No.
Regarding claim 1: As set forth above, steps a-c are interpreted to be insignificant extra-solution activities that are required in order to make the selection recited in step d. The limitation “to obtain a preparation” is interpreted to be an intended use of the fraction.
Regarding claims 2-5, 8, 10-14 and 16-17: The claims further limit step b. Step b is considered to be an insignificant extra-solution activity required in order to make the determination and selection recited in step d.
Regarding claims 7 and 15: The claims further limit the lysate recited in step a. As set forth above, step a is interpreted to be an insignificant extra-solution activity that is required in order to make the selection recited in step d.
Regarding claim 21: the claim recites the donor platelets are non-activated. This limitation does not add significantly more to the judicial exception. The claim further limits the pooling step of claim 1, which is an insignificant extra-solution activity required to make the selection recited in step d.
Claim 22 recites the determining step comprises one of the claimed measurements. The determining step is an significant extra-solution activity that is required in order to make the selection recited in step d.
Claim 23 recites assays used to perform the determining step in claim 1. The determining step is an significant extra-solution activity that is required in order to make the selection recited in step d.
Therefore claims 1-5, 7-8, 10-17 and 21-23 are not eligible subject matter under 35 USC 101.
APPLICANT’S ARGUMENTS
The arguments made in the response filed on 26 May 2026 are acknowledged.
Argument 1: The Applicant argues step c) of claim 1 is not a mental process because it explicitly requires determining an in vitro effect. The Applicant argues the specification discloses tests which require physical laboratory procedures.
Response to Argument 1: Because a measurement is required to make the determination recited in step c it is not interpreted to be a judicial exception. Since the determination does not require a specific assay, it does not integrate the judicial exception. The determining step is an significant extra-solution activity that is required in order to make the selection recited in step d.
Argument 2: The Applicant argues step d recites a physical step of isolating a fraction.
Response to Argument 2: Step d does not recite isolating a fraction. Step d recites “selecting” a fraction. The specification does not define “selecting”. Selecting which fraction to use based on data is a mental process (a judicial exception). The claim recites “to obtain a preparation…”. This is an intended use which does not require isolation. Therefore the arguments are not persuasive.
Argument 3: The Applicant argues the enriched fraction is useful in treating various diseases and conditions. The Applicant argues obtaining a fraction integrates the judicial exceptions into a practical application
Response to Argument 3: Claim 1 is not interpreted to isolate a fraction. The claims do not require treatment. Therefore the argument is not persuasive.
Argument 4: The Applicant argues claims 22 and 23 recite measurements and assays that cannot be performed mentally.
Response to Argument 4: While the claims further limit step c of claim 1, the selecting recited in step d is a judicial exception. Therefore the arguments are not persuasive.
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.
Claim 23 is 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 23: ELISpot and Luminex are trademarks. Where a trademark or trade name is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of 35 U.S.C. 112(b) or pre-AIA 35 U.S.C. 112, second paragraph. See Ex parte Simpson, 218 USPQ 1020 (Bd. App. 1982). The claim scope is uncertain since the trademark or trade name cannot be used properly to identify any particular material or product. A trademark or trade name is used to identify a source of goods, and not the goods themselves. Thus, a trademark or trade name does not identify or describe the goods associated with the trademark or trade name. In the present case, the trademark/trade name is used to identify/describe an assay/device and, accordingly, the identification/description is indefinite.
Claim Rejections - 35 USC § 103
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claims 1-5, 7-8, 10-17 and 21-23 are rejected under 35 U.S.C. 103 as being unpatentable over Behfar et al. (previously cited; Exosome Delivery Technology. Patent 10596123 with benefit of US20160324794 filed on 11 March 2016) in view of Torreggiani et al. (Exosomes: Novel Effectors of Human Platelet Lysate Activity. European Cells and Materials Vol. 28 2014 (pages 137-151) and Dinkla et al. (Platelet microparticles inhibit IL-17 production by regulatory T cells through P-selectin. 21 April 2016) as evidenced by Van Deun (The impact of disparate isolation methods for extracellular vesicles on downstream RNA profiling. Journal of Extracellular Vesicles, 3(1) pages 1-14) and Malys et al. (Small extracellular vesicles are released ex vivo from platelets into serum and from residual blood cells into stored plasma. J Extracell Biol. 2023 May 12;2(5):e88).
Behfar teaches a method of isolating and purifying exosomes (column 3, lines 50-52; see Figure 3). As evidenced by the specification, exosomes are extracellular vesicles ([0002] of PG Pub). The art teaches isolation from human blood (column 3, line 65). Therefore the extracellular vesicles are human. The exosomes are recovered from a platelet rich solution following physical disruption of platelets (same cited section; Figure 6). Disrupted platelets are interpreted to read on a platelet lysate. The art teaches filtration and concentration to obtain a concentrated desired product (see entire Figure 6). The exosomes are 30-100 nm in diameter (column 3, lines 53-56). Because the art obtains exosomes which are 30-100 nm in diameter, particles bigger than 200 nm have been removed.
As evidenced by Van Deun et al., exosomes are EVs that express a characteristic set of proteins: heat-shock protein (HSP)90a, HSP70 and CD63 (see page 1, left column). As evidenced by the specification, CD63 is a tetraspanin ([0044] of PG Pub). As evidenced by Van Deun, exosomes do not express GM130, a marker for Golgi apparatus (see page 5, right column, first paragraph). Therefore the isolated, purified exosomes taught by Behfar would inherently have the claimed characteristics.
Behfar teaches the product can be characterized by analyzing capacity to foster cell growth in vitro and pre-clinical performance (column 4, lines 50-56).
The deficiencies of Behar are:
The art does not teach pooled donated platelets incubated at 20-24°C.
The art does not teach determining an immune suppressive effect in vitro, and selecting a fraction determined to have said effect to obtain the claimed preparation.
Torreggiani generates a human platelet lysate (page 138, left column, third paragraph). Torreggiani collects and pools platelet units (page 138, left column, first paragraph of “Materials and Methods”). Exosomes are isolated (page 138, left column, second paragraph of “Materials and Methods”). The exosomes have a size of 30-100 nm (see page 137, right column, second paragraph).
Dinkla teaches platelets release platelet-derived microparticles (PMPs) into circulation (page 1976, left column, first paragraph). Dinkla analyzes the effect of PMPs regulatory T cells (Treg) (page 1976, right column, last paragraph). The art teaches PMPs inhibit the differentiation of Tregs into IL-17 and IFN-γ-producing cells. These findings indicate PMPs actively regulate the immune response at sites of injury (page 1977, left column, second paragraph).
Dinkla also teaches the following:
Single donor platelet rich plasma was collected from 3 donors. Platelets are collected and stored at 22°C ±2°C (page 1977, left column, Methods section, third paragraph).
It would have been obvious to pool donor platelets. Behfar isolates EVs from platelets and Torreggiani collects and pools platelet units to isolate EVs. One would have been motivated to do so to obtain a greater number of platelets for EV isolation. One would have had a reasonable expectation of success since Torreggiani teaches EVs can be isolated from pooled donor platelets. It would have been obvious to incubate the platelets at a 22°C ±2°C. One would have been motivated to do so since Dinkla teaches storage at 22°C ±2°C before processing to obtain microparticles (EVs). One would have had a reasonable expectation of success since Dinkla teaches platelets can be stored at the claimed temperature prior to use. One would have expected similar results since each reference is directed to a method of isolating EVs.
It would have been obvious to determine an immunosuppressive effect of the extracellular vesicles taught by Behfar. One would have been motivated to do so since Behfar teaches characterizing the function of platelet EVs and Dinkla teaches isolated EVs can be analyzed for an immunosuppressive effect. Because Behfar teaches the use of EVs as a therapeutic, one would test the obtained EVs to assess their pre-clinical efficacy as taught by Behfar. The skilled artisan would select the exosomes that exhibit the desired immune effect in vitro for subsequent clinical use. One would have had a reasonable expectation of success since Dinkla teaches the immune effect of isolated EVs can be analyzed. One would have expected similar results since both references are directed to platelet derived EVs. Therefore claim 1 is rendered obvious.
Torreggiani teaches platelet lysate was centrifuged to remove cellular debris (see page 138, last column). Therefore depletion of lysed cells, fragments and other debris is rendered obvious. Claim 2 is included in this rejection.
As evidenced by Malys et al. platelet extracellular vesicles express CD9, CD63 and CD41b (see page 4, last paragraph). Therefore the isolated, purified exosomes taught by Behfar would inherently express these markers. Claim 3 is included in this rejection.
As evidenced by Malys, small EVs (sEVs) are exosomes (see page 2, second paragraph). As evidenced by Malys, platelet sEVs lack CD81 (see page 4, second paragraph of section 3.1). Therefore the isolated, purified exosomes taught by Behfar would inherently be negative for CD81. Claim 4 is included in this rejection.
Behfar teaches filtration (supra). Therefore claim 5 is included in this rejection.
Torreggiani teaches pooled platelet units (supra). The art does not teach at least 40 donors.
It would have been obvious to pool platelet units for the reasons set forth above. While Torreggiani does not teach the use of at least 40 donors, MPEP 2144.04 (IV)(A) states: “In re Rinehart, 531 F.2d 1048, 189 USPQ 143 (CCPA 1976) ("mere scaling up of a prior art process capable of being scaled up, if such were the case, would not establish patentability in a claim to an old process so scaled." 531 F.2d at 1053, 189 USPQ at 148.).” Therefore claim 7 is rendered obvious as claimed.
Behfar teaches isolated, purified exosomes. Therefore they are interpreted to be cell free. Even arguendo it did not, Torreggiani teaches removing cell debris (supra). Therefore a cell-free preparation is rendered obvious. Claim 8 is included in this rejection.
Behfar teaches exosomes that are 30-100 nm in diameter (supra). Therefore claims 10-12 are rendered obvious.
As evidenced by Malys et al. platelet extracellular vesicles express CD9, CD63 and CD41b (see page 4, last paragraph). Therefore the isolated, purified exosomes taught by Behfar would inherently express these markers. Claim 13 is included in this rejection
Behfar teaches the exosomes can be concentrated by at least 5x (Figure 6). Behfar teaches exemplary yields (liquid volumes) are 10-40% and 20-30%, respectively for each step of processing (column 4, lines 5-9). The skilled artisan would optimize the concentration to achieve the desired amount of exosome in a given volume. Therefore claim 14 is included in this rejection.
Claim 15 is directed to the method of obtaining human platelet lysate. This is a product by process limitation that does not distinguish the claimed lysate from that of the prior art. MPEP 2113 indicates that “[E]ven though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process.” In re Thorpe, 777 F.2d 695, 698, 227 USPQ 964, 966 (Fed. Cir. 1985) (citations omitted). MPEP 2113 further indicates that “The Patent Office bears a lesser burden of proof in making out a case of prima facie obviousness for product-by-process claims because of their peculiar nature” than when a product is claimed in the conventional fashion. In re Fessmann, 489 F.2d 742, 744, 180 USPQ 324, 326 (CCPA 1974). Therefore claim 15 is included in this rejection.
As evidenced by Behfar, exosomes contain RNA (column 1, line 58). Therefore claim 16 is included in this rejection. As evidenced by Robbins, EVs contain messenger RNA (mRNAs), non-coding RNA (ncRNAs) including miRNAs (page 1, last 4 lines). Therefore claim 17 is included in this rejection.
Torreggiani teaches pooled platelets (supra). The art does not teach activation with a thrombocyte activator. Therefore claim 21 is included in this rejection.
Dinkla teaches coculture of Tregs with PMPs reduced Treg (immune cell) proliferation (see page 1981, right column). Claim 22 is included in this rejection.
In Figure 3, Dinkla analyzes the effect of PMPs on Treg (immune cells) using flow cytometry). Therefore claim 23 is included in this rejection.
Therefore, Applicant’s Invention is rendered obvious as claimed.
CONCLUSION
No Claims Are Allowed
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 extension fee 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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to NATALIE MOSS whose telephone number is (571) 270-7439. The examiner can normally be reached on Monday-Friday, 8am-5pm EST.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Sharmila Landau can be reached on (571) 272-0614. The fax phone number for the organization where this application or proceeding is assigned is (571) 273-8300.
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/NATALIE M MOSS/ Examiner, Art Unit 1653
/SHARMILA G LANDAU/Supervisory Patent Examiner, Art Unit 1653
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