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 .
Applicant’s amendments and arguments of April 14, 2026, are entered.
Claims 1-9 and 14 have been amended.
Claims 11-12 and 15 have been canceled.
No new claims.
Specification
The objection to the disclosure for containing grammatical errors in Paragraphs [0052] and [0053] is withdrawn.
Claim Rejections - 35 USC § 112
Based on Applicant’s amendments, Claim 14 being rejected under 35 U.S.C. §112(a) or 35 U.S.C. §112 (pre-AIA ), first paragraph, as failing to comply with the enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is not nearly connected, to make and/or use the invention is withdrawn.
Based on Applicant’s amendments, Claims 2, 4, and 10 being 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35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention are withdrawn.
Claim Rejections - 35 USC § 112
Based on Applicant’s amendments, Claims 2-17 being 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or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention are withdrawn.
Claim Rejections - 35 USC § 103
Based on Applicant’s amendments, Claims 1-17 rejection under 35 U.S.C. §103 as being unpatentable over Shiga et al. [Freeze-dried human platelet-rich plasma retains activation and growth factor expression after an eight-week preservation period, Asian Spine J., 2017], in view of Godoi et al. [Platelet-rich plasma gel matrix (PRP-GM): description of a new technique, Bioengineering, Dec. 19, 2022], in view of Ralsonics Surface Engineering Solutions (Hereinafter Ralsonics) [Using Sonicators in the Pharma Industry, 2018], in view of Emerson [WO 2016 153590 A2, 2016], is withdrawn.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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 for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 1-10, 13-14, and 16-17 are newly rejected under 35 U.S.C. §103 as being unpatentable over Andia et al. [Freeze-drying of platelet-rich plasma: the quest for standardization, International Journal of Molecular Sciences, 2020], in view of Shiga et al. [Freeze-dried human platelet-rich plasma retains activation and growth factor expression after an eight-week preservation period, Asian Spine J., 2017], in view of Godoi et al. [Platelet-rich plasma gel matrix (PRP-GM): description of a new technique, Bioengineering, Dec. 19, 2022], in view of Ralsonics Surface Engineering Solutions (Hereinafter Ralsonics) [Using Sonicators in the Pharma Industry, 2018].
Regarding claim 1, Andia et al., discussing multiple methods for platelet rich plasma preservation, teaches platelet containing composition comprising platelet rich plasma and platelet poor plasma where preparing anticoagulated whole blood can be either single spun or double spun resulting in either platelet rich plasma or platelet concentrate, i.e. high purity [Figure 2]. Andia et al. further teaches that platelet pellets can be resuspended in a determined amount of platelet poor plasma for purposes of adjusting concentration. Andia et al. also discloses that activation can be either through the use of calcium chloride/thrombin or by sonication [Id.]. Additionally, Andia et al., citing Pan et al. [12], discloses that products should be calcium activated prior to freeze-drying [2.1 Lyophilized PRP preservation ¶ 3].
For claim 2 where the platelet-containing composition is added to a form a colloid or liquid, Shiga et al. discloses two different scenarios for activation where in one example 100 microliters of calcium chloride and 100 microliters of thrombin solution are added to platelet-rich plasma where, initially, a liquid is formed prior to formation of fibrin [4. Platelet activation]. The other example includes adding buffered saline to platelet-rich plasma resulting in a liquid [5. Assessment of platelet activation via flow cytometry ¶ 1]. Furthermore, Andia et al. teaches that platelet concentrate can be resuspended where this would be understood by a person of ordinary skill in the art would mean a number of different states such as liquid suspension, colloidal mixture, semi-gel, etc. [Fig. 2]. Given this, there is a reasonable expectation of success that a person of ordinary skill in the art would combine the teachings of Andia et al. with the further teachings of Shiga et al. in order to combine a platelet rich concentrate that with platelet poor plasma to adjust concentration and further activating the platelet rich plasma composition prior to freeze drying given that Andia et al. disclosed this method in order to avoid reduced kinetics of certain growth factors. Because of this, it would have been prima facie obvious to a person of ordinary skill in the art prior to the filing of the claimed invention to modify the systems and methods of Andia et al. that discussed the many different protocols for preserving platelet rich plasma with the further teachings of Shiga et al. that also discloses various methods for preserving platelet rich plasma compounds.
For claim 3, Godoi et al teaches every limitation except Godoi et al. does not teach freeze drying, performing sterilization, and completing the preparation of platelets-containing composition, e.g. elements 5-7. However, Shiga et al. discloses the use of lyophilization and sterilization on platelet-rich plasma [Methods, Discussion ¶ 4]. Shiga et al. further discloses activating the lyophilized platelet-rich plasma using a calcium chloride solution [4. Platelet activation ¶ 1].
For claim 4 where an additive is added and the platelet-containing composition is used in colloid or liquid form, Andia et al. teaches the use of calcium chloride/thrombin [Fig. 2]. Furthermore, Andia et al. teaches that platelet concentrate can be resuspended where this would be understood by a person of ordinary skill in the art would mean a number of different states such as liquid suspension, colloidal mixture, semi-gel, etc. [Id.].
For claims 5-8 where the additive is in the range of 0.01 ~ 10% Ca2+, Shiga et al. discloses a 100 microliters of calcium chloride for 10-15mL of platelet-rich plasma, the calcium chloride represents roughly 0.66 to 0.99% [4. Platelet activation ¶ 1].
For claim 9 where a gel is prepared in shape and thickness for irregular wounds or bone repair/protection, Godoi et al. discloses the use of platelet-rich plasma where it has been evaluated and established in numerous musculoskeletal conditions that include osteoarthritis, tendinopathies, and osteonecrosis, as well as stimulating wound healing in patients. Furthermore, it would have been obvious to a person of ordinary skill in the art that platelet-rich plasma compositions, e.g. gels, used for wound healing are typically molded or shaped to conform to the dimensions of the specific wound site to ensure optimal coverage and contact with the relative tissue. Such shaping would have been routine and predictable practice in the art and would be considered prima facie obvious to a skilled artisan applying platelet-rich plasma composition gels for therapeutic purposes.
For claim 10 where the additive is a solvent and the platelet composite solution is formed, Shiga et al. discloses the use where lyophilized platelet-rich plasma can be incorporated into artificial bone after being dissolved in water [Discussion ¶ 4].
For claim 13 where the quantifying platelet-rich plasma is through centrifugation and adding water for injection to adjust platelet concentration, both Andia et al. and Shiga et al. discloses the use of centrifugation as a method for concentrating platelets [Fig. 2, Introduction ¶ 1]. Furthermore, it would have been obvious to a person of ordinary skill in the art at the time of the claimed invention to dilute platelet-rich plasma using a sterile, pharmaceutically acceptable diluent such as water for injection, as the use of such diluents for adjusting the volume or concentration of biologically active suspensions was well known and routine. Furthermore, it would have been routine for a skilled artisan to determine the appropriate platelet concentration for a particular therapeutic application through standard experimentation, including diluting and measuring platelet counts, without undue experimentation. Based on this, there is a reasonable expectation of success to combine platelet-rich plasma with a well-known diluent, e.g. water for injection, for the purpose of adjusting platelet concentration to a desired level and would have been within the ordinary skill of the art and thus, prima facie obvious.
For claim 14 where quantification is achieved using a certain substitute for water for injection, Shiga et al. discloses the use of buffered saline for purposes of activation. However, it would have been prima facie obvious to a person of ordinary skill in the art prior to the filing of the claimed invention to dilute platelet-rich plasma with a pharmaceutically acceptable diluent, e.g. normal saline or isotonic saline to adjust the volume of concentration of biologically active suspensions given these methods are well known in the art and would have allowed a skilled artisan the ability to determine an appropriate platelet concentration for a particular therapeutic application.
For claim 16 where an activator is added to the platelet rich plasma and supernatant is removed by centrifugation and mixed with the platelet-poor plasma, One of ordinary skill in the are would have recognized activation of platelet rich plasma followed by centrifugation and removal of supernatant as routine platelet-processing techniques used to isolate platelet secretome fractions containing growth factors. Furthermore, resuspending or mixing such fractions with platelet poor plasma to adjust composition or formulation characteristics would have been considered routine. Both instances represent routine manipulation and recombination of known platelet fractions using standard processing methods.
For claim 17 where ultrasonication is used to mix the platelet rich plasma, i.e. high concentrated platelet plasma, with the platelet poor plasma, Andia et al. and Ralsonics disclose using sonicators as a means for mixing solutions and accelerating the dissolution process [Fig. 2, Particle Agitation].
Here, it would have been prima facie obvious to a person of ordinary skill in the art prior to the filing of the claimed invention to modify the systems and methods of Andia et al. and Shiga et al. with the further teachings of Godoi et al. where the authors developed a platelet rich plasma gel matrix with the additional teachings of Ralsonics where sonication is used in mixing, agitating, and/or accelerating the dissolution process for pharmaceutical compounds. Given this, there is a reasonable expectation of success that a skilled artisan would recognize the teachings of Andia et al. and Shiga et al. and combine these with Godoi et al. and Ralsonics for the purpose of creating platelet rich plasma compositions from lyophilized platelet rich plasma that was mixed with platelet poor plasma prior and mixed and/or agitated with a sonicator as an activator for further mixing.
The Supreme court has acknowledged:
When a work is available in one field of endeavor, design incentives and other market forces can prompt variations of it, either in the same field or a different one. If a person of ordinary skill can implement a predictable varition..103 likely bars its patentability…if a technique has been used to improve one device, and a person of ordinary skill in the art would recognize that it would improve similar devices in the same way, using the technique is obvious unless its actual application is beyond that person’s skill. A court must ask whether the improvement is more than the predictable use of prior-art elements according to their established functions…
…the combination of familiar elements according to known methods is likely to be obvious when it does no more than yield predictable results (see KSR International Co. v. Teleflex Inc., 82 USPQ2d 1385 U.S. 2007) emphasis added.
In KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398 (2007), the Supreme Court reaffirmed "the conclusion that when a patent 'simply arranges old elements with each performing the same function it had been known to perform' and yields no more than one would expect from such an arrangement, the combination is obvious." Id. at 417 (quoting Sakraida v. Ag Pro, Inc., 425 U.S. 273,282 (1976)). The Supreme Court also emphasized a flexible approach to the obviousness question, stating that the analysis under 35 U.S.C. § 103 "need not seek out precise teachings directed to the specific subject matter of the challenged claim, for a court can take account of the inferences and creative steps that a person of ordinary skill in the art would employ." Id. at 418; see also id. at 421 ("A person of ordinary skill is... a person of ordinary creativity, not an automaton.").
From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
Response to Argument
Applicant’s argument regarding non-analogous art is not persuasive because the cited references are directed to the same field of endeavor as the claimed invention, namely platelet rich plasma processing, activation, preservation, and therapeutic formulation. Andia et al. expressly teaches PRP and PPP fractionation, platelet concentration by centrifugation, resuspension or platelet pellets in PPP, i.e. high purity, platelet activation using either calcium chloride/thrombin or sonication, and lyophilized PRP formulations. Andia et al. also specifically discloses the use of activators prior to lyophilization. Shiga et al. teaches freeze-dried PRP compositions that retain activation capability and growth factor expression after preservation, while Godoi et al. teaches activated PRP gel matrices for sustained biological effect. Each reference is reasonably pertinent to the problem being addressed by Applicant, i.e. preparation of stabilized platelet compositions hiving retained growth factor activity.
Furthermore, the references collectively provide sufficient motivation to combine the teachings because the consistently identify known goals including PRP standardization, preservation of platelet activity, stabilization of growth factors, and controlled biological delivery from activated platelet compositions. Therefore, one of ordinary skill in the art would have found it obvious to combine the known PRP concentration, PPP mixing, activation, and freeze-drying techniques taught by the references to obtain the claimed platelet-containing composition. Because of this, Claims 1-10, 13-14, and 16-17 are newly rejected under 35 U.S.C. §103.
Conclusion
No claims 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 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.
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/JOHN DAVID MOORE/Examiner, Art Unit 1638
/PETER PARAS JR/Supervisory Patent Examiner, Art Unit 1632
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