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 1-4, 6-7, 9-21, and 23-24 are pending (claim set as filed on 02/06/2026).
Applicant’s election without traverse of Group I, method claims drawn to a process of making/producing, in the reply filed on 11/14/2024 is acknowledged. Claims 11-19 and 23 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.
Therefore, only claims 1-4, 6-7, 9-10, 20-21, and 24 are under examination.
Priority
This application is a 371 of PCT/US2020/032018 filed on 05/08/2020, which provisional applications to 62/971,425 filed on 02/07/2020, and 62/845,140 filed on 05/08/2019.
Withdrawal of Rejections
The response and amendments filed on 02/06/2026 are acknowledged. Any previously applied minor objections and/or minor rejections (i.e., formal matters), not explicitly restated herein for brevity, have been withdrawn necessitated by Applicant’s formality corrections and/or amendments. For the purposes of clarity of the record, the reasons for the Examiner’s withdrawal, and/or maintaining if applicable, of the substantive or essential claim rejections are detailed directly below and/or in the Examiner’s response to arguments section.
The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application.
Maintained Rejections
Claim Rejections - 35 USC §103, Obviousness
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 1-4, 6-7, 9-10, and 21 are rejected under 35 U.S.C. 103 as being unpatentable over Weissman (US 2014/0179602 A1) in view of Burnouf (EP 2 077 118 A1, citations made to the equivalent pre-grant publication US 2011/0027257 A1 - cited by the ISA and in the IDS filed on 09/05/2023) and Chen (US 2018/0273898 A1 - newly cited).
Weissman’s general disclosure relates to a viral inactivated biological liquid or dry mixture and to its preparation; in particular, a viral inactivated platelet extract and preparation thereof (see abstract & ¶ [0001]).
Weissman teaches “method for preparing a viral-safe biological liquid mixture, the method comprising the following steps: providing a biological liquid mixture; carrying out a solvent detergent (S/D) viral inactivation treatment; contacting the S/D treated mixture with an amphiphilic polymer; removing the S/D by hydrophobic interaction chromatography (HIC) and/or by oil extraction; collecting a material comprising a flow through fraction from HIC and/or a liquid fraction from oil extraction; and subjecting the material to at least one more orthogonal viral inactivation treatment” (see ¶ [0012], [0231]-[0236], [0178], [0193]). Weissman teaches a step of concentrating the material (see ¶ [0023]) and “the HIC comprises the steps of: washing with a solution comprising an organic solvent and/or a salt; and collecting a washed fraction” (see ¶ [0035]); wherein the salt is NaCl (saline) (see ¶ [0039]).
Regarding claims 3-4 and 9 pertaining to the washing and separation, Weissman teaches the platelet pellet is washed at least twice (with centrifugation between the washes) with saline under gentle conditions (see ¶ [0102], [0136], [0198]) and further teaches centrifugation at 1000xg for 4 minutes at room temperature or the sample was continuously stirred for 30 minutes, centrifuged at 5016xg for 10 minutes at 23-27° C (see ¶ [0212], [0282], [0345]).
Regarding claim 6, Weissman teaches “the washing is carried out as follows: a platelet material unit is centrifuged under gentle conditions. Then, the supernatant is discarded and the platelet pellet is washed at least twice (with centrifugation between the washes) with saline under gentle conditions. The washed and re-suspended platelets can be frozen until used” (see ¶ [0102]).
Regarding claim 10, Weissman teaches “the method comprises preparing a platelet lysate. The term ‘lysate’ refers to a solution produced when cells are destroyed by disrupting their cell membranes. Lysis of the platelets and release of the factors (e.g., various platelet growth factors and/or trophic factors) entrapped in the platelets, can be carried out by freezing and thawing the platelets enriched fractions, by S/D treatment, by sonication” (see ¶ [0084]-[0086]).
Regarding claim 21, Weissman teaches “cryoprecipitate refers to a blood component which is obtained from frozen plasma prepared from whole blood. A cryoprecipitate can be obtained when frozen plasma is thawed in the cold, typically at a temperature of 0-4° C., resulting in the formation of precipitated supernatant that contains fibrinogen and factor XIII. The precipitate can be collected, for example by centrifugation” (see ¶ [0156]).
However, Weissman does not teach: washing the platelets with buffered saline without calcium or magnesium (claim 1’s limitation iii); or the detergent in buffered saline (claim 1’s limitation iv) selected from TRITON X-114, NP-40, CHAPS, or TWEEN 20 (claims 7 and 24).
Burnouf relates to methods of preparation of platelet derivatives (see ¶ [0013]). Burnouf teaches “the method of the invention comprises a preliminary step consisting in preparing a starting platelet concentrate, said starting platelet concentrate being prepared by apheresis or by buffy-coat isolation from whole blood, and being either fresh, expired and stored liquid or expired and stored frozen” (see ¶ [0018], [0066]-[0068]).
Regarding the buffered saline, Burnouf teaches “the cells were washed with phosphate-buffered saline (PBS)” (see ¶ [0114]). Claim interpretation: PBS is a commonly used buffer solution in cell culture which contains phosphate and sodium chloride (saline) and thus, it reads on the amended claim limitation of “buffered saline without calcium or magnesium”.
Regarding the detergent, Burnouf teaches the use of detergent selected from polyoxyethylene derivatives of fatty acids, partial esters of sorbitol anhydrides, non-ionic detergents, sodium deoxycholate and sulfobetaines, and more preferably in the group consisting in Triton X-45, Triton X-100, Tween 80 and Tween 20 (see ¶ [0016], [0055]). Burnouf further teaches the step of solvent-detergent removal (see ¶ [0019]).
Regarding the detergent in buffered saline, Chen teaches “a rinse process is performed to rinse the surface substance. The rinse process includes the steps of: rinsing the surface substance three times with a phosphate-buffered saline containing Tween-20; rinsing the surface substance once with a phosphate-buffered saline without Tween-20; and rinsing the surface substance once with deionized water. The rinse process removes the loosely adsorbed proteins” (see ¶ [0032]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to first wash the cells with phosphate buffered saline (PBS) such as taught by Burnouf in the method of Weissman. The MPEP 2141 provides examples of rationales that may support a conclusion of obviousness include: (a) combining prior art elements according to known methods to yield predictable results; or (b) simple substitution of one known element for another to obtain predictable results. As noted above, PBS is a common and routinely used buffer solution in cell culture and therefore, it is within the purview of the ordinary artisan to employ PBS for simple washing/rinsing of the platelets. Furthermore, it would have been secondly obvious to substitute or employ the detergent of Tween 20 such as taught by Burnouf or Chen’s PBS-detergent in the method of Weissman. The ordinary artisan would have been motivated to do so because Burnouf teaches the detergents are used in the method of preparation or obtaining platelet derivatives and Chen teaches the rinse process including PBS-detergent-Tween 20 facilitates removing loosely absorbed proteins. The ordinary artisan would have had a reasonable expectation of success because both Weissman and Burnouf are in the same field of endeavor directed to methods of preparations to obtain platelet products.
Claim 20 is rejected under 35 U.S.C. 103 as being unpatentable over Weissman in view of Burnouf and Chen as applied to claims 1-4, 6-7, 9-10, and 21 above, and in further view of Ho (US 2008/0032405 A1 - previously cited).
Weissman and Burnouf’s disclosures are taught above as it pertains to a method of preparing a platelet extract.
However, modified-Weissman-Burnouf-Chen does not teach: wherein the whole blood is an equine whole blood and the washed platelet extracted produced is a washed equine platelet extract (claim 20).
Ho teaches various origins, such as human, porcine, bovine, equine, avian, caprine, or ovine, but are preferably of primate origin, and most preferably of human origin (see ¶ [0011]). Ho teaches separation, conventional lysis techniques, and “chemical treatments typically consist of exposing the erythrocytes to detergents or surfactants that cause rupture of the membranes. Examples of detergents and surfactants suitable for lysis are NP-40 and other nonylphenol ethoxylates, alkyl aryl polyether alcohols such as TRITON® X-100, BRIJ 58 (polyoxyethylene cetyl ether), CHAPS (a sulfobetaine-type zwitterionic detergent), and sodium dodecyl sulfate. When a detergent or surfactant is used, the appropriate concentration will be readily apparent to those skilled in the art” (see ¶ [0011]).
It would have been obvious to use equine whole blood such as suggested by Ho as the source in Weissman-Burnouf-Chen as this is within the purview and selection of the ordinary artisan. The MPEP 2141 provides examples of rationales that may support a conclusion of obviousness include: (b) simple substitution of one known element for another to obtain predictable results. The ordinary artisan would have had a reasonable expectation of success because both Weissman-Burnouf and Ho are in the same field of endeavor directed to methods of preparations to obtain cell products.
Examiner’s Response to Arguments
Applicant’s amendments and arguments filed on 02/06/2026 have been fully considered but they are not persuasive and deemed insufficient to overcome the prior arts of record.
In response to Applicant’s argument (addressing bridging ¶ of pages 5-6 of the remarks) that Weismann does not teach the claim’s steps pertaining separating plasma from whole blood then platelets from the plasma as the starting material in Weismann’s method is the platelet sample: this argument is not persuasive because in determining the differences between the prior art and the claims, the question under 35 U.S.C. 103 is not whether the differences themselves would have been obvious, but whether the claimed invention as a whole would have been obvious (MPEP 2141.02(I)). Moreover, the determination of obviousness is not particularly restricted to the exact language or particular examples disclosed by the references but it also includes the common knowledge and understanding of a person having ordinary skill in the art (a PHOSITA). In this instance, both the claimed invention and the primary reference of Weismann are directed a platelet extract and its preparation thereof. It is common knowledge to a PHOSITA to obtain platelets from separated whole blood source (e.g., it is a routine procedure to draw blood into test tubes for placement into a centrifuge apparatus to separate the blood components based upon density or specific gravity components). Weismann discloses various blood fractions from donor sources. In particular, Weismann discloses “Typically, the term ‘platelet starting material’ relates to platelet-enriched fractions obtained from more than one donor for use in the method of the invention. The platelet enriched fractions can be, for example, separated from units of whole blood, from blood fractions and/or from plasma fractions” (note that ¶ [0102] refers back or encompasses the preceding ¶ [0097]-[0101] which discloses the donor sources and blood fractions).
In response to Applicant’s argument (addressing 1st full ¶ of page 6 of the remarks) that Burnouf’s “wash step is not part of the platelet extraction process, and there is no suggestion that it should be” and that “PBS without calcium or magnesium is a specialized formulation, and is not standard”: this argument is not persuasive because note that in the primary reference of Weismann at ¶ [0102], Weismann teaches “the term "washed platelets" refers to platelets which were subjected to a washing step. During the washing procedure there can also be losses of platelets. The washing can be carried out using 0.9% sodium chloride with or without small amounts of dextrose ... In one embodiment of the invention, the washing is carried out as follows: a platelet material unit is centrifuged under gentle conditions. Then, the supernatant is discarded and the platelet pellet is washed at least twice (with centrifugation between the washes) with saline under gentle conditions. The washed and re-suspended platelets can be frozen until used in the method of the invention”. The practice of washing platelets with 0.9% sodium chloride (sodium chloride is saline which is NaCl and thereby, is without calcium or magnesium) and centrifuging is a routine practice or expedient to a PHOSITA. Moreover, the prior office action on page 5 stated that “Regarding the buffered saline, Burnouf teaches “the cells were washed with phosphate-buffered saline (PBS)” (see ¶ [0114]). Claim interpretation: PBS is a commonly used buffer solution in cell culture which contains phosphate and sodium chloride (saline) and thus, it reads on the amended claim limitation of “buffered saline without calcium or magnesium”. PBS is a solution that laboratory technicians routinely use to wash cell products (maintains the pH) and the prior arts have no mention of said solution containing any calcium or magnesium and moreover, having calcium would likely activate the clotting cascade causing coagulation.
In response to Applicant’s argument (addressing 2nd full ¶ of page 6 of the remarks) that “there is nothing in Weismann or the other cited references that suggests that the lysate should be separated at a drastically different temperature than what is disclosed. Applicant notes that Weismann’s separation step also requires filtration”: this argument is not persuasive because as noted in Weismann at ¶ [0102] which discloses “a platelet material unit is centrifuged under gentle conditions. Then, the supernatant is discarded and the platelet pellet is washed at least twice (with centrifugation between the washes) with saline under gentle conditions. The washed and re-suspended platelets can be frozen until used in the method of the invention” and at page 5 of the prior office action, Weissman teaches “cryoprecipitate refers to a blood component which is obtained from frozen plasma prepared from whole blood. A cryoprecipitate can be obtained when frozen plasma is thawed in the cold, typically at a temperature of 0-4°C., resulting in the formation of precipitated supernatant that contains fibrinogen and factor XIII. The precipitate can be collected, for example by centrifugation” (see ¶ [0156]). Thus, the temperature would be dependent upon whether the blood component is frozen or cryopreserved for later use. Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. Where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation (MPEP 2144.05(II)(A)). In regards to Applicant’s note about Weismann’s separation step also requires filtration, the claim’s transitional phrase of “comprising” is open-ended and does not exclude additional, unrecited elements or method steps (MPEP 2111.03(I)).
In response to Applicant’s argument (addressing page 7 of the remarks) that the cited references use harsh solvents suitable for suitable viral inactivation, they would not be suitable for yielding high platelet recovery, integrity, and abundance of platelet-derived growth factors as demonstrated in the present application: this argument is not persuasive because as noted above, the claim’s transitional phrase is comprising which is open-ended and therefore, it does not exclude other solvents. Both the present application and cited references desire a viral inactivation and note that Burnouf discloses “the method of the invention increases significantly the recovery of all, at least of the more important platelet growth factors, and more particularly of growth factors PDGF” (see Burnouf at ¶ [0013] where PDGF stands for platelet derived growth factor).
In response to Applicant’s argument (addressing bridging ¶ of pages 7-8 of the remarks) that Chen uses PBS-Tween 20 for the purpose of rinsing a parylene film to remove loosely adsorbed proteins and is not used for cell lysis: this argument is not persuasive because one cannot show non-obviousness by attacking references individually where the rejections are based on combinations of references. Detergents have known functions for cell lysis. For example, the primary reference of Weismann teaches “the S/D treatment also promotes lysis of the platelets and release of their content into the solution” (see Weismann at ¶ [0096]) or Burnouf teaches platelet lysis with 1% Triton X-45 (see Burnouf at ¶ [0132], [0138]).
In response to Applicant’s argument (addressing page 8 of the remarks) that “The instant application teaches a method of preparing a wash platelet extract free of immunogenic serum plasma proteins, such as albumin, fibrinogen, and immunoglobulins. See, e.g. ¶ [0027]-[0028]”: this argument is not persuasive because although the claims are interpreted in light of the specification, limitations from the specification are not imported into the claims. In other words, there is no mention in the claims of these features.
In response to Applicant’s argument (addressing bridging ¶ of pages 8-9 of the remarks) that Triton-X114 provides the added advantages of being removable by centrifugation and allowing removal of endotoxin from the washed platelet extract: it is noted that the specification discloses “Yield efficiency was calculated as amount of PDGF per total protein respect to the one obtained from PRP (Table 1). Amongst tested detergents, Triton X-114 2% was most efficient in yielding a protein rich platelet extract 266-fold higher than PRP (Table 1). Equine IgG were detected only in the PRP (150±5 mg/mL) and no trace of IgG could be detected in the extracts derived from washed platelets, independently of the lysis detergent used. Similarly, no albumin or fibrinogen could be detected in the equine platelets extract generated with 2% Triton X-114 (Table 1). No endotoxin was detected in the final preparations (detection limit of the kit was 0.06 endotoxin units (EU)/mL).” (see pre-grant specification at ¶ [0087] & Table 1). This is objective evidence of unexpected results and thus, incorporating all of these features into the base claim to be in commensurate in scope with the unexpected results to be non-obviousness.
In response to Applicant’s argument (addressing page 9 of the remarks) that “Ho discloses making a whole blood-based substitute designed to function as a standard, reference, control, or calibrator for clinical blood coagulation assays. The blood-based substitute material is washed to remove platelets, which is antithetical to the goals of Weissman and Burnouf”: this argument is not persuasive because the disclosure of Ho was primarily relied upon to address the use equine whole blood and not as a standard control assay.
New Grounds of Rejection Necessitated by Amendment
Claim Rejections - 35 USC §103, Obviousness
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 7 and 24 are rejected under 35 U.S.C. 103 as being unpatentable over Weissman in view of Burnouf and Chen as applied to claims 1-4, 6-7, 9-10, and 21 above, and in further view of Schnecker (US 2019/0142908 A1 - newly cited).
Weissman, Burnouf, and Chen’s disclosures are taught above as it pertains to a method of preparing a platelet extract.
However, the cited references do not teach: the detergent selected from TRITON X-114 (claims 7 and 24).
Schnecker teaches the surfactant is selected from the group consisting of digitonin, Triton X-100, Triton X-114, TWEEN-20, TWEEN-80 (see claim 11).
It would have been obvious to use Triton X-114 such as suggested by Schnecker in Weissman-Burnouf-Chen as this is within the purview and selection of the ordinary artisan. The MPEP 2141 provides examples of rationales that may support a conclusion of obviousness include: (b) simple substitution of one known element for another to obtain predictable results. The ordinary artisan would have had a reasonable expectation of success because all of the references are in the same field of endeavor directed to methods of preparations to obtain cell products.
Conclusion
No claims were 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.
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/NGHI V NGUYEN/Primary Examiner, Art Unit 1653
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