DETAILED ACTION
This action is in reply to papers filed 12/17/2025. Claims 1 and 5-16 are pending and examined herein.
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 .
Election/Restrictions
Applicant previously elected without traverse of Group I, drawn to claims 1 and 4-17, in the reply filed on 08/12/2025. Claims 2-3, 20-34, and 36-49 are withdrawn from consideration as being drawn to a non-elected invention.
Withdrawn Objection(s) and/or Rejection(s)
The cancellation of claims 4 and 17 renders any rejections thereof moot.
The rejection of claim 1 under 35 U.S.C. 112(b) is withdrawn in light of amendment made to the claim to address the lack of antecedent basis regarding the limitation “step of inactivation” (line 4).
The rejection of claim 14 under 35 U.S.C. 112(b) is withdrawn in light of amendment made to the claim to delete the phrase "e.g." (line 3).
The rejection of claim 16 under 35 U.S.C. 112(b) is withdrawn in light of amendment made to the claim to replace the limitation “a subject” with “the individual” (line 3).
The rejection of claims 1 and 6-16 under 35 U.S.C. 102(a)(1) as being anticipated by Shih (New Biotechnology, 2015, 32(1): 199-211) is withdrawn in light of amendment made to claim 1, which recites “freezing and thawing platelets obtained from the individual or equivalents thereof to obtain a platelet lysate two or more times” (lines 3-4).
Claim Interpretation
The following terms are defined in the specification and are used for the purposes of examination:
“Individual” is defined as “any individual biological entity.” Furthermore, the specification recites that “genetically equivalent individuals, even if separate, are considered identical individuals for the purposes of this disclosure” (p 11, para 9).
“Platelet lysate” is defined as “a combination of growth factors contained in platelets released by lysing the platelets” (p 12, para 12).
“Inactivation” is defined as “an operation performed to deactivate complement components in serum” (p 12, para 13).
The specification recites that “mesenchymal stem cell” is also referred to as a “mesenchymal stromal cell, and refers to a stem cell that have the ability to differentiate into cells belonging to the mesenchymal system” (p 12, para 14).
According to the specification, “platelets obtained from an individual" encompasses “so-called primary cell platelets as well as equivalents thereof, i.e., platelets genetically equivalent to the individual” (p 12, para 11). Therefore, the phrase “equivalents thereof” in line 3 of claim 1 is interpreted as referring back to “the individual” in line 3.
Claim 1, which is drawn to a method of preparing a platelet lysate, recites an intended use for the platelet lysate (“for use in culturing cells obtained from an individual” in lines 1-2). The intended use does not impose additional limitations to the method as claimed, and therefore is not given patentable weight. See MPEP 2111.02(II).
Claims 11 and 16, which depend from claim 1, impose limitations on the cells recited in the intended use clause of claim 1. Claims 12-15 depend indirectly from claim 1 and impose additional imitations on the cells of claim 1. The cells are not used in or made by the method, are recited as an intended use, and do not materially alter the lysate composition as currently claimed. Accordingly, the wherein clauses recited in claims 11-16 that further limit “the cells” of claim 1 are not given patentable weight as they likewise do not affect the breadth of the claim 1. However, for the sake of compact prosecution, the limitations recited in claims 11-16 are considered in the context of prior art rejections below.
Claim Rejections - 35 USC § 112(b)
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.
Claims 1 and 5 are 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.
Claim 1, as amended, recites the limitation “freezing and thawing platelets obtained from the individual or equivalents thereof to obtain a platelet lysate two or more times” (lines 3-4). It is unclear whether the limitation “two or more times” refers 1) to the phrase “freezing and thawing platelets obtained from the individual or equivalents thereof,” implying that the step of freezing and thawing platelets takes place at least two times to obtain a platelet lysate, or 2) to the phrase “to obtain a platelet lysate,” implying that the step of freezing and thawing platelets is performed in parallel for multiple platelets obtained from the individual or equivalents thereof, to obtain at least two samples of platelet lysate. The first interpretation is used for the purpose of examination.
Claim 5 depends from cancelled claim 4. Therefore, the metes and bounds of the method claimed in claim 5 is unclear. For the purpose of examination, claim 5 is interpreted as depending from independent claim 1.
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.
Claim(s) 1 and 5-16 remain rejected under 35 U.S.C. 102(a)(1) and 35 U.S.C. 102(a)(2) as being anticipated by Woods (WO 2015/031465 A1; cited in IDS filed 01/30/2023).
As discussed in the claim interpretation section above, the limitations set forth in claims 11-16 do not impose additional limitations to the claimed methods, and therefore are not given patentable weight. However, for the sake of compact prosecution, the limitations in these claims are discussed below in the context of the prior art.
Woods discloses a method for preparing platelet lysate from human platelets, wherein the platelets are lysed by subjecting them to at least one freeze-thaw cycle, including two or three cycles (p 8, para 2) (claims 1, 5). Woods discloses that the freezing temperature of the platelet concentrate in the freeze-thaw cycle is between about -10℃ and -80℃ (p 8, para 2) (claims 6-10). The method disclosed in Woods does not comprise an inactivation step (claim 1). Woods discloses that platelet units from different donors can be pooled at some point during processing, implying that the pooling of platelets from different individuals is not required (p 8, para 1) (claim 1).
Woods discloses that the platelet lysate can be used as a component in cell culture media for the growth or maintenance of cells, including mesenchymal stem cells (p 21, para 2) (claims 11-13). Woods discloses that the platelet lysate can be used as a supplement in cell culture media for the culture of bone marrow mesenchymal cells, adipocyte stem cells, placenta-derived mesenchymal stem cells, or muscle-derived stem or progenitor cells (p 27, para 1) (claims 14-15).
Woods discloses that platelet lysates are used in culture media for the expansion of mesenchymal stem cells to be used for transplantation or administration in therapeutic treatment (reads on cells that are used in cell injection therapy of claim 16) (p 3, para 2-4).
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.
Claim(s) 1 and 5-16 are rejected under 35 U.S.C. 103 as being unpatentable over Shih (New Biotechnology, 2015, 32(1): 199-211), in view of Strandberg (Transplantation and Cellular Engineering, 2017, 57: 1058-1065).
As discussed in the claim interpretation section above, the limitations set forth in claims 11-17 do not impose additional limitations to the claimed methods, and do not have patentable weight. However, for the sake of compact prosecution, the limitations in these claims are discussed below in the context of the prior art.
Shih discloses that single-donor or autologous platelet lysates can be prepared from platelets by a freeze-thaw process, wherein the freezing temperature is -80℃ (p 205, col 2, para 2) (claims 1, 6-10). Shih discloses that autologous platelet lysates obtained using the freeze-thaw method can be used as a medium supplement for ex vivo stem cell expansion, including mesenchymal stromal cell (MSC) expansion (claims 11-13) (Fig. 1; p 205, col 2, para 2). The method disclosed in Shih does not comprise a step to inactivate complement components (p 205, col 1, para 3) (claim 1).
Shih discloses that MSC-based cell therapy can utilize MSCs derived from bone marrow, umbilical cord blood, adipose tissues, and dental pulp (claims 14-15) (p 199, col 2, para 2). Shih discloses that platelet lysates can be used to expand bone-marrow derived MSCs (p 200, col 2, para 3 – p 201, col 1, para 1) (claim 15).
Shih discloses that clinical applications using MSCs include treatments for bone diseases, repair of cartilage, control of graft versus host disease, facilitation of engraftment of bone marrow transplants, and treatment of myocardial infarction (reads on cell injection therapy of claim 16), and that for many clinical indications, MSCs must be isolated and expanded ex vivo (claims 16) (p 199, col 1 – col 2).
Shih does not teach freezing and thawing the platelets two or more times (claim 1) or three times (claim 5).
Strandberg teaches a method for preparing platelet lysates by subjecting plateletpheresis and platelet-poor plasma samples to freeze-thaw cycles (Abstract: Study design and methods). Strandberg teaches that utilizing three to five freeze-thaw cycles resulted in platelet lysates with optimal concentration of growth factors (Abstract: Conclusion).
It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method taught in Shih by freezing and thawing the platelets or equivalents thereof between three and five times, as taught in Strandberg. One of ordinary skill in the art would have been motivated to make this modification because Strandberg teaches that repeating the freeze-thaw cycle three to five times results in optimal concentration of growth factors in the prepared platelet lysates. One of ordinary skill in the art would have had a reasonable expectation of successfully making this modification because Strandberg teaches that platelets, or equivalents thereof, can be frozen and thawed for up to 30 times (Abstract: Study design and methods).
Response to Arguments
Claim Rejections - 35 USC § 102
Applicant argues: Woods and Shih teach single freeze-thaw cycles, whereas amended independent claim 1 requires multiple freeze-thaw cycles, as well as no step of complement inactivation. In fact, Shih explicitly teaches that one cycle is sufficient, essentially teaching away from the claimed multiple-cycle approach.
In response: Applicant's arguments have been fully considered but are not persuasive. Woods teaches subjecting platelets to multiple freeze-thaw cycles, including 2 or 3 freeze-thaw cycles, to release platelet contents (p 8, para 2).
Shih does not teach multiple freeze-thaw cycles, and therefore, the previous grounds of rejection under 35 USC 102 has been withdrawn. Importantly, however, Shih does not teach away from multiple freeze-thaw cycles. A reference does not teach away if it merely expresses a general preference for an alternative invention but does not criticize, discredit or otherwise discourage investigation into the invention claimed. See MPEP 2145(X)(D)(1), UCB, Inc. v. Actavis Labs, UT, Inc., 65 F.4th 679, 692, 2023 USPQ2d 448 (Fed. Cir. 2023). Therefore, claims 1 and 5-16 remain rejected under 35 USC 103 over Shih, in view of Strandberg, which teaches multiple freeze-thaw cycles, as set forth above.
Applicant further argues: Moreover, experimental data in the present application demonstrates significantly elevated trophic factors (PDGF, BDNF, etc.), as well as markedly improved proliferative activity only when complement inactivation is omitted, which is not taught or suggested in Woods or
Shih.
In response: Applicant's arguments have been fully considered but are not persuasive. In response to applicant's argument that the references fail to show certain features of the invention, it is noted that the features upon which applicant relies (i.e., that omitting the step of complement inactivation results in elevated trophic factors and improved proliferative activity) are not recited in the rejected claim(s). Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993).
Applicant further argues: Moreover, Additionally, Woods permits donor pooling, whereas amended independent claim 1 requires "freezing and thawing platelets obtained from the [same] individual ... ".
In response: Applicant's arguments have been fully considered but are not persuasive. Woods discloses that platelet units from different donors can be pooled at some point during processing, implying that the pooling of platelets from different individuals is not required (p 8, para 1). Thus, Woods anticipates the limitation of claim 1 that recites “freezing and thawing platelets obtained from the individual or equivalents thereof,” as set forth above in the rejection under 35 USC 102.
Claim Rejections - 35 USC § 103
Applicant argues: Strandberg's objective is growth factor enrichment, not complement preservation. Accordingly, there would have been no motivation to one having ordinary skill in the art to modify Shih with Strandberg's teaching, whatsoever, to provide a comparable method to that recited in amended independent claim 1.
In response: Applicant's arguments have been fully considered but are not persuasive. In response to applicant’s argument that there is no teaching, suggestion, or motivation to combine the references, the examiner recognizes that obviousness may be established by combining or modifying the teachings of the prior art to produce the claimed invention where there is some teaching, suggestion, or motivation to do so found either in the references themselves or in the knowledge generally available to one of ordinary skill in the art. See In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988), In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992), and KSR International Co. v. Teleflex, Inc., 550 U.S. 398, 82 USPQ2d 1385 (2007). In this case, Shih teaches a method for preparing human platelet materials as medium supplements for MSC isolation and expansion (Abstract), and Strandberg teaches a method for optimizing the concentration of growth factors in platelet lysate (Abstract). Shih teaches that successful MSC isolation and culture protocols require media with enriched growth factors (p 200, col 1, para 1). Shih further teaches that growth factor-rich platelet lysates allow for the ex vivo expansion of MSCs (p 207, col 1, para 1) and for therapeutic-scale stem cell expansion (p 208, col 2, para 3). Therefore, there was motivation to combine the teachings of Shih, which teaches the advantages of growth factor-rich platelet lysates for MSC isolation and expansion, with the teachings of Strandberg, which teaches a method for optimizing the concentration of growth factors in platelet lysate.
Applicant further argues: Moreover, as mentioned above, Shih explicitly discloses that only one freeze-thaw cycle is sufficient, which teaches away from performing multiple cycles, as claimed.
In response: Applicant's arguments have been fully considered but are not persuasive. Shih does not teach away from multiple freeze-thaw cycles. A reference does not teach away if it merely expresses a general preference for an alternative invention but does not criticize, discredit or otherwise discourage investigation into the invention claimed. See MPEP 2145(X)(D)(1), UCB, Inc. v. Actavis Labs, UT, Inc., 65 F.4th 679, 692, 2023 USPQ2d 448 (Fed. Cir. 2023).
Applicant further argues: Finally, the present application demonstrates that autologous PL yields unique proliferative advantages that cannot be obtained with allogeneic sources, as in the prior art.
In response: Applicant's arguments have been fully considered but are not persuasive. The primary reference, Shih, teaches the preparation of single-donor or autologous platelet lysates.
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 Risa Takenaka whose telephone number is (571)272-0149. The examiner can normally be reached M-F, 12-7 EST.
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/RISA TAKENAKA/Examiner, Art Unit 1632
/TITILAYO MOLOYE/Primary Examiner, Art Unit 1632