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 .
Priority
The instant application is a national stage entry under 35 U.S.C. § 371 of PCT/US2022/020115 (filed 03/14/2022). Acknowledgement is made of Applicants’ claim for benefit of U.S. Provisional Application No. 63/177,203 (filed 04/20/2021).
Response to Amendment
The amendment filed on 06/02/2026 has been received and entered into the application file.
Claim 12 has been canceled; claims 26-29 and 73-75 remain withdrawn.
Claims 1, 4, 7-8, 10-11, 13-14, 16, 18, 20, 22, and 24 are pending and examined on the merits herein.
Status of Prior Rejections/Response to Arguments
RE: Rejection of:
claims 1 and 10 under 35 U.S.C. 102(a)(1) and (a)(2) over Crowe;
claims 4 and 11-13 under 35 U.S.C. 103 over Crowe:
The cancelation of claim 12 renders its rejection moot.
The amendment to independent claims 1 and 11 recite the method as comprising adding prostaglandin-E1 to the blood, platelet-rich plasma, or apheresis platelets to form a solution thereof, and further recites the method is performed at atmospheric pressure; this amendment is effective to obviate the remaining rejections of record.
In view of this amendment, Applicants assert the method of the Crowe, et al. disclosure (hereinafter Crowe) is distinct from the method of the instant invention in that Crowe teaches freeze drying platelets via lyophilization, which is performed under vacuum and therefore necessarily at a pressure considerably lower than atmospheric pressure. This argument is found persuasive.
Accordingly, the remaining rejections of record are withdrawn.
RE: Rejection of:
claims 1, 4, and 10-13 under 35 U.S.C. 103 over Kuhn in view of Elliott;
claims 7-8 and 14 under 35 U.S.C. 103 over Kuhn in view of Elliott, further in view of Abcam®;
claims 16, 20, and 24 under 35 U.S.C. 103 over Kuhn in view of Elliott, further in view of Sigma®; and
claims 18 and 22 under 35 U.S.C. 103 over Kuhn in view of Elliott, further in view of Sigma® and Roser and Vos:
The cancelation of claim 12 renders its rejection moot.
The amendment independent claims 1 and 11 which recites the method as comprising adding prostaglandin-E1 to the blood, platelet-rich plasma, or apheresis platelets to form a solution thereof is effective to obviate the remaining rejections of record.
Applicants assert this amendment is sufficient to render independent claims 1 and 11 nonobvious over the combination of Kuhn, et al. (hereinafter Kuhn) and Elliot, et al. (hereinafter Elliot), further asserting a person of ordinary skill in the art would not have a reasonable expectation of success. This argument is found persuasive in regards to the previous rejection.
Accordingly, the remaining rejections of record are withdrawn.
New Grounds of Rejections
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1, 4, 7-8, 10-11, 13-14, 16, 18, 20, 22, and 24 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claims 1 and 11 have been amended to recite the limitation wherein the method is performed at atmospheric pressure; this is new matter. The new matter must be removed in response to this Office action.
Applicants have pointed to Examples 1 and 4 of the specification for support. However, Examples 1 and 4 have been reviewed, and are silent in regards to the atmospheric pressure. The only mention of atmospheric pressure in the specification is disclosed in Example 5, directed to lyophilization of cryopreserved platelets: “…the vials were transferred to a lyophilizer equilibrated to -40°C at atmospheric pressure for 4 hours. Vacuum was applied (100 mTorr)…”. This does not support the current claim amendment that the entire method is performed at atmospheric pressure, as lyophilization was requried (which is performed under vacuum). The Examiner acknowledges Figs. 10 and 11 compare activation of frozen platelets and lyophilized platelets; while lyophilization necessarily comprises lowering the pressure while freezing the product, thereby removing ice via sublimation, the step of lowering the pressure as compared to ambient pressure does not necessarily denote the ambient pressure as atmospheric pressure.
Thus, one of ordinary skill in the art, in looking to the instant specification, would not be able to determine that Applicants were in possession of the invention, as currently claimed, at the time the invention was made. Accordingly, the claims are considered to lack sufficient written description and are properly rejected under 35 U.S.C. 112(a).
Claims 4, 7-8, 11, 13-14, 16, 18, 20, 22, and 24 directly depend from or incorporate the subject matter of claims 1 and 11; therefore, these claims are also included in this rejection.
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.
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, 4, 10-11, and 13 are rejected under 35 U.S.C. 103 as being unpatentable over Kuhn, et al. (US 2020/0046771) in view of Polyak and Arrington (US 2002/0068268), Moskowitz, et al. (WO 2020/113101), and Elliott, et al. (US 2021/0205358).
Kuhn teaches compositions comprising cryopreserved platelets (Abstract).
Polyak and Arrington (hereinafter Polyak) teaches machine perfusion solutions for the preservation of organs and biological tissues (Abstract).
Moskowitz, et al. (hereinafter Moskowitz) teaches a method of preparing cargo-loaded platelets (Abstract).
Elliott teaches mitochondrial isolation and storage buffer (pars. 0121-0123).
Regarding claims 1, 11: Kuhn teaches a method comprising obtaining platelets and suspending the platelets in a medium comprising a cryoprotectant and subjecting the suspended platelets to a temperature sufficient to form a cryopreserved platelet composition (pars. 0027-0030), wherein the platelets are apheresis-derived (par. 0142) and the cryoprotectant is trehalose (par. 0035), disclosing an embodiment wherein the temperature is -80°C and the cooling rate is 1°C/min (par. 0323). Kuhn discloses an embodiment wherein the cryopreserved platelet composition is stored at -80°C (par. 0282), as well as an embodiment wherein the method further comprises thawing the composition in a water bath at 37°C (par. 0053). This renders obvious:
the method for cryopreserving platelets, the method comprising: (a) obtaining blood or platelet-rich plasma, or apheresis-derived platelets from a subject; (c) isolating platelets from the blood, platelet-rich plasma, or apheresis platelet solution; (d) suspending the platelets in a suspension buffer comprising trehalose; and (f) cooling the platelets to a temperature of about -80°C at a rate of about 2-20°C per minute; and (g) storing the platelets at about -80°C; wherein the method is performed at atmospheric pressure limitations recited in claim 1; and
the method for cryopreserving and recovering platelets from cryopreservation, the method comprising: (a) obtaining blood or platelet-rich plasma, or apheresis-derived platelets from a subject; (c) isolating platelets from the blood, platelet-rich plasma, or apheresis platelet solution; (d) suspending the platelets in a suspension buffer comprising trehalose; and (f) cooling the platelets to a temperature of about -80°C at a rate of about 2-20°C per minute; (g) storing the platelets at about -80°C; and (h) thawing the platelets at about 20-40°C; wherein the method is performed at atmospheric pressure limitations recited in claim 11.
Kuhn does not teach the limitations recited in steps (b) and (e) of claims 1 and 11.
Regarding step (b):
Polyak teaches prostaglandin E1 (PGE1) has cellular and organelle membrane stabilization properties, cryoprotective properties, and ability to prevent platelet aggregation (par. 0015). Moskowitz teaches cryopreservation of platelets after incubating platelets with PGE1 at 37°C for 3 hours and then washing the platelets (par. 00297).
Therefore, it would have been prima facie obvious to a person having ordinary skill in the art to have modified the method of Kuhn by incorporating a step wherein the platelets are incubated in prostaglandin E1 prior to their suspension in the trehalose solution. This conclusion of obviousness is based on the ‘teaching, suggestion, or motivation rationale’. One would be motivated to do so for the cryoprotection, membrane stabilization, and prevention of platelet aggregation, as taught by Polyak; further, as Moskowitz teaches cryopreservation of platelets after incubation with PGE1, the skilled artisan would have more than a reasonable expectation of success.
This renders obvious the limitations recited in step (b) of claims 1 and 11.
Regarding step (e):
Elliott teaches bovine serum albumin (BSA) is a membrane stabilizer (par. 0121).
Therefore, it would have been prima facie obvious to a person having ordinary skill in the art to have further modified the method of Kuhn by adding BSA into the medium comprising the platelets and trehalose. This conclusion of obviousness is based on the ‘teaching, suggestion, or motivation rationale’; one would be motivated to include BSA for additional membrane stabilization during the cryopreservation process, as taught by Elliott. Further, as adding BSA to buffers is a well-known technique in the art, as evidenced by Elliott, a skilled artisan would have more than a reasonable expectation of success.
This renders obvious the limitations recited in step (e) of claims 1 and 11.
Further, as the modified method of Kuhn set forth above carries out the same active steps recited in claims 1 and 11, the effect of maintaining viability and activation potential recited in the preamble of these claims is necessarily achieved, rendering the remaining limitation of the instant claims obvious.
Regarding claims 4, 13: Following the above discussion, Elliott does not teach the BSA concentration at 4% by mass, as recited in the limitations of the instant claims. However, the BSA concentration would have been routinely optimized by a person having ordinary skill in the art based on the other culture conditions. Elliott clearly teaches BSA is added at a concentration effective to achieve membrane stabilization; that means the conditions necessarily to achieve the membrane stabilization were result effective variables. Result effective variables would be optimized by routine experimentation by one having ordinary skill in the art. Furthermore, differences in concentration will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration is critical. See MPEP 2144.05(II)(A). This renders obvious the limitations of claims 4 and 13.
Regarding claim 10: Following the above discussion, the cryopreserved platelet composition of the modified method of Kuhn reads on the cryopreserved platelets limitation recited in claim 10.
Claims 7-8 and 14 are rejected under 35 U.S.C. 103 as being unpatentable over Kuhn, et al. (US 2020/0046771) in view of Polyak and Arrington (US 2002/0068268), Moskowitz, et al. (WO 2020/113101), and Elliott, et al. (US 2021/0205358); further in view of Abcam® (“Isolation of Human Platelets”; 2014).
The teachings of Kuhn, Polyak, Moskowitz, and Elliott are set forth above.
Abcam® teaches isolation of human platelets from whole blood (Title).
Regarding claim 7: Following the above discussion, Kuhn teaches an embodiment wherein the platelets are isolated by centrifugation at 1500 x g for 20 minutes (par. 0292), but does not teach the specific centrifugation limitations of the instant claim.
However, Abcam® teaches a protocol for platelet isolation comprising a first centrifugation spin at 100 x g for 15-20 minutes to pellet any contaminating red and white blood cells, followed by transferring the supernatant comprising pellets into a new tube for a second centrifugation spin at 800 x g for 15-20 min to pellet the platelets ( “Platelet isolation”; pg. 2). While the method discloses the second centrifugation step at 800 g instead of 1000 g, the centrifugation force would have been routinely optimized by an ordinary artisan. Abcam® clearly teaches the second centrifugation step is performed at a gravitational force effective to pellet the platelets; that means the gravitational force required to achieve said pellet is a result effective variable. Result effective variables would be optimized by routine experimentation by one having ordinary skill in the art. See MPEP 2144.05(II)(A). Thus, the protocol taught by Abcam® renders obvious the wherein isolating the platelets comprises centrifugation of the blood, platelet-rich plasma, or apheresis platelets at 100 x g for 15 minutes to generate a first pellet and a first supernatant; followed by centrifugation of the first supernatant at 1000 x g for 15 minutes to generate a second pellet and a second supernatant, wherein the first supernatant is platelet-rich and the second supernatant is platelet-poor limitations recited in claim 7.
It would have been prima facie obvious for a person having ordinary skill in the art to have further modified the method of Kuhn by substituting the single-step centrifugation protocol with the two-step centrifugation protocol disclosed by Abcam®. This conclusion of obviousness is based on the ‘substitution rationale’; given that both Kuhn and Abcam® teach centrifugation to pellet platelets, there was a reasonable expectation that both protocols would work equivalently. Substitution of one element for another known in the field wherein the result of the substitution would have been predictable is considered to be obvious. See MPEP 2144.06(II).
Therefore, the modified method set forth above renders obvious the limitations recited in claim 7.
Regarding claim 8: Following the above discussion, Abcam® teaches 1-3 x 108 platelets/mL is an appropriate concentration for various downstream applications using platelets after isolation (“Platelet isolation”; pg. 3); this reads on the concentration of about 1 x 106 platelets/µL limitation recited in the instant claim. Kuhn teaches the trehalose cryoprotectant is at a concentration of about 40 mM to 100 mM (par. 0015); this reads on the trehalose is added to about 50 mM limitation recited in claim 8.
Regarding claim 14: Following the above discussion, Kuhn teaches after isolation via centrifugation, the platelets are incubated at 37°C for 3 hours with gentle agitation before transferred for freezing (pars. 0294-0295); this reads on the wherein the diluted platelets are incubated at about 37°C for about 2 hours with periodic agitation limitation recited in claim 14.
Claims 16, 20, and 24 are rejected under 35 U.S.C. 103 as being unpatentable over Kuhn, et al. (US 2020/0046771) in view of Polyak and Arrington (US 2002/0068268), Moskowitz, et al. (WO 2020/113101), and Elliott, et al. (US 2021/0205358); further in view of Sigma® (“Monoclonal anti-human CD62P”; 1997).
The teachings of Kuhn, Polyak, Moskowitz, and Elliott are set forth above.
Sigma® teaches a monoclonal anti-human CD62P antibody and procedure for indirect immunofluorescence staining of human platelets (Titles; pgs. 1, 2).
Regarding claims 16, 20: Following the above discussion, Kuhn teaches activation assessment of the cryopreserved platelet composition by analyzing CD62P expression using flow cytometry (pars. 0398-0401), but does not explicitly teach the specifics thereof.
However, Sigma® teaches a procedure for the indirect immunofluorescence staining of human platelets using a monoclonal anti-human CD62P antibody (pg. 2). Specifically, Sigma® teaches a method comprising centrifuging a platelet suspension at 1000 x g for 15 minutes and removing the supernatant before adding ADP reagent and then incubating for 5 minutes; next, cold 1% paraformaldehyde solution in PBS is added before a 1 hour incubation, followed by addition of 3 mL of diluent before centrifugation at 1000 x g for 10 minutes; following centrifugation, after the supernatant is removed, the platelets are resuspended in diluent, which comprises PBS with 1% BSA (“Reagents”, “Procedure”; pg. 2). This reads on the initial centrifugation at 1000 x g for 15 minutes limitation recited in step (i) of claim 16, and the platelets resuspended in diluent comprising PBS with 1% BSA limitation recited in step (j) of claim 16.
Sigma® teaches the second centrifugation step at 1000 x g for 10 minutes, not 15 minutes; however, the duration of the second centrifugation step would have been routinely optimized by one having ordinary skill in the art. Sigma® clearly teaches the duration of the second centrifugation step is at a duration effective to pellet the platelets (“Procedure”; pg. 2); this means the duration of the second centrifugation step is a result effective variable. Result effective variables would be optimized by routine experimentation by one having ordinary skill in the art. The second centrifugation step following the addition of diluent taught by Sigma® renders obvious the limitation recited in step (i-1) of claim 20.
It would have been prima facie obvious to a person having ordinary skill in the art to have further modified the method of Kuhn by using the flow cytometry protocol using the monoclonal anti-human CD62P antibody taught by Sigma®. This conclusion of obviousness is based on the ‘teaching, suggestion, or motivation rationale’. One would have been motivated to do so because Kuhn teaches activation assessment of the cryopreserved platelet composition by analyzing CD62P expression using flow cytometry (pars. 0398-0401), and it would have been obvious to use a known protocol to carry out the activation assessment. Additionally, as both Kuhn and Sigma® teach flow cytometry using a CD62P antibody for the assessment of platelet activation, one would have more than a reasonable expectation of success.
Thus, this modified method renders obvious the limitations recited in claims 16 and 20.
Regarding claim 24: Following the above discussion, Kuhn teaches the cryopreserved platelet composition can be stored for 18 months or longer (par. 0282); this reads on the wherein the period of time in step (g) is from 1 day to about 5 years limitation recited in claim 24.
Claims 18 and 22 are rejected under 35 U.S.C. 103 as being unpatentable over Kuhn, et al. (US 2020/0046771) in view of Polyak and Arrington (US 2002/0068268), Moskowitz, et al. (WO 2020/113101), and Elliott, et al. (US 2021/0205358); further in view of Sigma® (“Monoclonal anti-human CD62P”; 1997) and Roser and Vos (US 2001/0046487).
The teachings of Kuhn, Polyak, Moskowitz, Elliott, and Sigma® are set forth above.
Roser and Vos (hereinafter Roser) teaches methods for drying platelets to obtain compositions which are storage stable over a wide range of temperatures (Abstract).
Regarding claims 18, 22: Following the above discussion, the modified method of Kuhn does not teach the limitations recited in the instant claims.
However, Roser teaches trehalose stabilizes the cell membrane under stressful conditions (par. 0010), disclosing its concentration for use as a stabilizing agent from 0.1 to 20%, i.e., about 3 mM to about 584 mM (par. 0050); this renders obvious the 50mM trehalose limitation recited in claims 18 and 22.
It would have been prima facie obvious to a person having ordinary skill in the art to have further modified the method of Kuhn by including trehalose in the diluent. This conclusion of obviousness is based on the ‘teaching, suggestion, or motivation rationale’; one would be motivated to include trehalose in the diluent for the cell membrane stabilization, as taught by Roser. Further, as both Kuhn and Roser teach the use of trehalose in platelet compositions, a skilled artisan would have more than a reasonable expectation of success.
This renders obvious the limitations recited in claims 18 and 22.
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 mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to GINA PRONZATI whose telephone number is (571)270-5725. The examiner can normally be reached Monday - Friday 9:00a - 5:00p ET.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, CHRISTOPHER BABIC can be reached at (571)272-8507. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/GINA PRONZATI/Examiner, Art Unit 1633
/ALLISON M FOX/Primary Examiner, Art Unit 1633
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