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).
Election/Restrictions
Applicant’s election of Group I in the reply filed on 01/15/2026 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Claims 1, 4, 7-8, 10-14, 16, 18, 20, 22, and 24 read on the elected invention and are examined on the merits herein.
Claim Rejections - 35 USC § 102
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1 and 10 are rejected under 35 U.S.C. 102(a)(1) and (a)(2) as being anticipated by Crowe, et al. (US 2006/0134069).
Crowe, et al. teaches a process for preserving and/or increasing the survival of dehydrated erythrocytic cells (Abstract).
Regarding claim 1: Crowe, et al. teaches a method wherein platelets were isolated from the platelet rich plasma of volunteers (par. 0184); this reads on the limitations recited in steps (a) and (b) of claim 1. The platelets were then incubated in a buffer with 35 mM trehalose and resuspended in a drying buffer comprising human serum albumin (par. 0185); as Crowe, et al. teaches the drying buffer assists in stabilizing platelet membranes (par. 0106), this reads on the limitation recited in steps (c) and (d) of claim 1. Crowe, et al. teaches the platelet suspensions were transferred to cryogenic vials prior to transfer to a -80°C freezer for storage, with an optimal freezing rate between 2°C and 5°C per minute (par. 0198); this reads on the limitations recited in steps (e) and (f) of claim 1. As the method taught by Crowe, et al. carries out the same active steps, the effect of maintaining viability and activation potential is necessarily achieved.
Regarding claim 10: Following the above discussion, the frozen platelets of Crowe, et al. reads on the cryopreserved platelets limitation recited in claim 10.
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, and 10-13 are rejected under 35 U.S.C. 103 as being unpatentable over Crowe, et al. (US 2006/0134069), as evidenced by Gläfke, et al. (Biotechnol Prog. 2012).
The teachings of Crowe, et al. are set forth above; claims 1 and 10 are anticipated by Crowe, et al.
Regarding claim 4: Following the above discussion, Crowe, et al. does not teach the drying buffer for membrane stabilization as comprising bovine serum albumin (BSA), disclosing human serum albumin (HSA) instead (pars. 0106, 0185). However, it would have been prima facie obvious to a person having ordinary skill in the art to have modified the method of Crowe, et al. by substituting BSA for HSA. This conclusion of obviousness is based on the ‘substitution rationale’. Crowe, et al. teaches a method for freeze-drying mesenchymal stem cells using 5.7% BSA instead of HSA in the drying buffer (par. 0207), which reads on the BSA at about 4% by mass limitation recited in claim 4; thus, there was a reasonable expectation that BSA and HSA 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). This renders obvious the limitation recited in claim 4.
Regarding claim 11: Following the above discussion, Crowe et al. teaches the concentration of trehalose in the cryopreservation medium may vary, and considerations of the cryopreservation protocol including procedural steps used for thawing the cells may affect the efficiency and efficacy of the trehalose concentration (par. 0126). Thus, the Crowe, et al. disclosure implicitly teaches thawing the platelets after cryopreservation for further use. Therefore, it would have been prima facie obvious to a person having ordinary skill in the art to have modified the method of Crowe, et al. by thawing the platelets for further use, as implicitly disclosed. Additionally, it would have been obvious to thaw the cells at 37°C because, as evidenced by Gläfke, et al., thawing frozen cell aliquots in a 37°C water bath is well known in the art (pg. 1348; col. 2, par. 1), and one would have a reasonable expectation of success for the same reason. This renders obvious the limitations recited in claim 11.
Regarding claim 12: Following the above discussion, Crowe et al. teaches an embodiment wherein the concentration of trehalose ranges from about 10 mM to about 50 mM (par. 0126); this renders obvious the limitation recited in claim 12.
Regarding claim 13: Following the above discussion, it would have been prima facie obvious to a person having ordinary skill in the art to have likewise substituted BSA for HSA in the method of Crowe, et al. comprising a thawing step, and for the same reasons as set forth above, rendering obvious the limitation recited in claim 13.
Claims 1, 4, and 10-13 are rejected under 35 U.S.C. 103 as being unpatentable over Kuhn, et al. (US 2020/0046771) in view of Elliott, et al. (US 2021/0205358).
Kuhn, et al. teaches compositions comprising cryopreserved platelets (Abstract).
Elliott, et al. teaches mitochondrial isolation and storage buffer (pars. 0121-0123).
Regarding claims 1, 11: Kuhn, et al. 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); this reads on the limitations recited in steps (a), (b), (c), and (e) of claims 1 and 11. Kuhn, et al. 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 reads on the limitations recited in step (f) of claim 1 and steps (f) and (g) of claim 11.
Kuhn, et al. does not teach adding a stabilizing agent to the platelet composition, as required by the limitation recited in step (d) of claims 1 and 11.
However, Elliott, et al. teaches bovine serum albumin (BSA) is a membrane stabilizer (par. 0121); this is relevant to the limitation recited in step (d) of claims 1 and 11.
Therefore, it would have been prima facie obvious to a person having ordinary skill in the art to have modified the method of Kuhn, et al. 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 the membrane stabilization, as taught by Elliott, et al. Further, as adding BSA to buffers is a well-known technique in the art, as evidenced by Elliott, et al., a skilled artisan would have more than a reasonable expectation of success.
As the modified method of Kuhn, et al. 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 claim 1 is necessarily achieved, as well as the method for cryopreserving and recovering platelets from cryopreservation recited in the preamble of claim 11, rendering the limitations of the instant claims obvious.
Regarding claims 4, 13: Following the above discussion, Elliott, et al. 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, et al. 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, et al. reads on the cryopreserved platelets limitation recited in claim 10.
Regarding claim 12: Following the above discussion, Kuhn, et al. teaches the trehalose cryoprotectant is present at about 40 mM to 100 mM (pars. 0015-0016); this reads on the wherein the suspension buffer comprises about 50 mM trehalose limitation recited in claim 12.
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 Elliott, et al. (US 2021/0205358), further in view of Abcam® (“Isolation of Human Platelets”; 2014).
The teachings of Kuhn, et al. and Elliott, et al. are set forth above.
Abcam® teaches isolation of human platelets from whole blood (Title).
Regarding claim 7: Following the above discussion, Kuhn, et al. 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 disclosed 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, et al. 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, et al. 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, et al. 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, et al. 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 Elliott, et al. (US 2021/0205358), further in view of Sigma® (“Monoclonal anti-human CD62P”; 1997).
The teachings of Kuhn, et al. and Elliott, et al. 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, et al. 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).
The initial centrifugation at 1000 x g for 15 minutes reads on the limitation recited in step (h) of claim 16. The platelets resuspended in diluent comprising PBS with 1% BSA reads on the limitation recited in step (i) 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. Therefore, the second centrifugation step following the addition of diluent taught by Sigma® renders obvious the limitation recited in step (h-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, et al. 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, et al. 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, et al. 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, et al. 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 (f) 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 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, et al., Elliott, et al., 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, et al. 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, et al. 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, et al. 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
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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/GINA PRONZATI/Examiner, Art Unit 1633
/ALLISON M FOX/Primary Examiner, Art Unit 1633