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 .
DETAILED ACTION
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
This application is in response to the papers filed on April 23, 2025 for a Request for Continued Examination. Pursuant to the amendment filed on April 23, 2025, claims 1-2, 5-15, 17 and 19-24 are currently pending. Claims 9-15 and 17-20 were previously withdrawn in the Office Action dated May 8, 2024. Claim 17 has been amended, claim 18 has been cancelled, and claims 22 -24 are newly filed in Applicant’s amendment filed on April 23, 2025.
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on April 23, 2025 has been entered.
Therefore, claims 1-2, 5-8 and 21-24 are currently under examination to which the following grounds of rejection are applicable.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on April 23, 2025 was filed. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Response to Arguments
Withdrawn Objections/Rejections in response to Applicants’ arguments or amendments:
Claim Rejections - 35 USC § 112
In view of Applicants’ amendment to the claims dated February 28, 2025, wherein claims 1 and 21 have been amended, the rejection to claims 1-2, 5-8 and 21 rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite, are withdrawn. The rejections are withdrawn because claims 1 and 21 have been amended to now recite “dry platelet lysate”.
In view of Applicants’ amendment to the claims dated February 28, 2025, wherein claims 1 and 21 have been amended, the rejection to claims 1-2, 5-8 and 21 rejected under 35 U.S.C. 103 as being unpatentable over Weissman et al (US 2012/0156306 A1 (Patent No. US 8,603,541 B2)) in view of Muraglia et al. (Platelets 25.3 (2014): 211-220) are now withdrawn. The rejections are withdrawn due to Weissman in view of Muraglia not clearly stating the outcomes of using the viral inactivated platelet lysate for cell cultivation that has been inactivated with UV treatment whererin one of two the treatments being UV treatments.
Applicants’ arguments are moot in view of the withdrawn rejection. A response to any argument pertaining to a new or maintained rejection can be found below.
Maintained Objections/Rejections in response to Applicants’ arguments or amendments:
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.
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.
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, 2, 5-8, and 21-24 are rejected under 35 U.S.C. 103 as being unpatentable over Muraglia et al. (Platelets 25.3 (2014): 211-220; of record) in view of Weissman et al (US 2012/0156306 A1 (Patent No. US 8,603,541 B2); of record) and Viau et al. (PLoS One 12.8 (2017): e0181406.).
Claim 1 is directed to a method for producing a material for preparing a substrate for cultivating living cells, said method comprising: providing a blood platelet lysate, drying said blood platelet lysate as to provide a dry platelet lysate material, and exposing said dry platelet lysate material to at least two different treatments, wherein each of the at least two different treatments inactivates virus particles and/or virus components, so as to provide a virus-free or at least virus-reduced dry platelet lysate material.
Regarding claim 1, Muraglia teaches the freeze-drying of blood platelet lysate (PL) followed by exposure to gamma radiation treatment for subsequent use in tissue culturing (p 2, col 2, par 2-5). The platelet lysate was irradiated at different dosage of gamma radiation, i.e., 0.1, 1, 5 and 25 KGy (p 2, col 2). The PL was shown to promote cell proliferation when compared to a fetal calf serum standard culture even across a range of starting cell densities (500, 2000, and 4000 cells/well), and moreover at lower concentrations (0.5 -1%) (FCS; Fig. 7A, 7B). Muraglia describes “the standardized PRP formulation would provide an “off-the-shelf” product to be used for the selection and expansion of several cell types also in critical cell culture conditions.” (abstract). Thus, Muraglia supports freeze-drying of blood platelet lysate (PL) followed by viral inactivation via exposure to gamma radiation.
Muraglia does not teach two different treatments wherein each of the at least two different treatments inactivates virus particles and/or virus components, so as to provide a virus-free or at least virus-reduced dry platelet lysate material.
However, Weissman discloses a method for producing a material for preparing a substrate for cultivating living cells (“The platelet extract prepared according to the invention can be used in combination with various cell types e.g. fibroblast and stem cells e.g. endothelial stem cells e.g. HUVEC.” (par 0130)), said method comprising: providing a blood platelet lysate, exposing said platelet lysate material to at least two different treatments, wherein each of the at least two different treatments inactivates virus particles and/or virus components, so as to provide a virus-free or at least virus-reduced platelet lysate material, and drying said blood platelet lysate as to provide a viral inactivated dry platelet lysate material (“providing a platelet-enriched fraction from multiple donors e.g. a washed and/or leukocyte-reduced platelet fraction from aphaeresis pooled from multiple donors; preparing a platelet lysate; carrying out a solvent detergent (S/D) viral inactivation treatment; removing the S/D by hydrophobic interaction chromatography (HIC), wherein the HIC comprises the steps of: loading the lysate to HIC, and collecting a material eluted under non isocratic conditions; and conducting a second orthogonal viral inactivation treatment.” (par 0016); “A combination of two or more of the following non limiting treatment examples can be used: pasteurization, Solvent/Detergent (S/D), nanofiltration, Low pH treatment, UV irradiation and Sodium thiocyanate treatment.” (par 0084); heat inactivation treatment (par 0064-66)). Weissman further states the advantage of the taught invention is that it “solves a long felt need for a viral safe (at least double viral inactivated) platelet protein extract obtained from multiple donors comprising a mixture of proteins having growth factor and/or trophic factor activity.” (par 0013)).
The combined teachings of Muraglia and Weissman teach the outcomes of UV and gamma irradiation for viral inactivation of PL for cell cultivation, and Weissman teaches the combination of different treatments for complete viral inactivation of platelet lysate that are necessary for pooled platelet products.
Viau teaches a “clinical grade human Platelet Lysate (hPL) that constitutes an advantageous substitute for fetal bovine serum (FBS) for human mesenchymal stem cell (hMSC) expansion required in cell therapy procedures, avoiding xenogenic risks (virological and immunological) and ethical issues... based on short-wave ultraviolet light (UV-C) that induces non-reversible damages in DNA and RNA of pathogens while preserving protein structures and functions, and has the main advantage of not needing the addition of any photosensitizing additives (that might secondarily interfere with hMSCs)... We demonstrated the feasibility of using UV-C-treated platelets to subsequently obtain pathogen-reduced hPL, while preserving its optimal quality and efficacy for hMSC expansion in cell therapy applications.” (abstract). The treatment occurred on fresh (liquid) platelet concentrates (PC) wherein platelet lysate was prepared from these PCs.
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the Muraglia method of drying a platelet lysate followed by a viral inactivation treatment by using another viral inactivation treatment for which Weissman does to obtain a safe, platelet lysate product. This would be obvious in view of the different treatments discloses by Weissman, i.e. heat inactivation and UV treatment, which is further supported by Viau, that were shown to be effective and safe to then be used in cell culturing by using UV-C. As a whole, it was shown that treatments using UV and gamma irradiation for platelet lysates were effective in reducing viruses while also maintaining the capability of being used in cell culturing.
Regarding claim 2, dependent on claim 1, the combined teachings of Muraglia, Weissman and Viau render obvious claim 1. Muraglia teaches exposure to gamma radiation treatment for subsequent use in tissue culturing (p 2, col 2, par 2-5). The platelet lysate was irradiated at different dosage of gamma radiation, i.e., : 0.1, 1, 5 and 25 KGy (p 2, col 2).
Additionally, Weissman teaches a method wherein the treatments comprise at least two different treatments selected from the group consisting of: pasteurization, Solvent/Detergent (S/D), nanofiltration, Low pH treatment, UV irradiation and Sodium thiocyanate treatment (par 0084). Furthermore, Weissman teaches “The extract according to the invention has one or more of the following advantages: is standardized and allows robust (consistent) biological performance; exhibits biological activity e.g. induction of proliferation and/or morphological changes in cells;… has optimal viral safety;” (par 0082)).
Viau teaches the irradiation of platelet concentrates (PCs) with UV-C treatment at a standard illumination dose of 0.2 J/cm2 was used (Materials & Methods, par 1).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the Muraglia’s treatment to include Weissman’s second orthogonal viral inactivation treatment based on such treatment being used for inactivating viral particles in which the PL product promoted cell proliferation as described in the claim 1 rejection above. Moreover, Weissman teaches the numerous advantages of using different treatments as seen in the obtained platelet lysate product, wherein the product has improved safety, exhibits biological activity, and is formed by a standardized method. Furthermore, it would have been obvious to select. UV and Gamma irradiation as an orthogonal treatments for preparing a substrate for cultivating living cells based on these taught outcomes.
Regarding claim 5, the combined teachings of Muraglia, Weissman and Viau render obvious claim 1. Additionally, Weissman teaches wherein the blood platelet lysate is dried by lyophilization (par 0176).
Regarding claim 6, the combined teachings of Muraglia, Weissman and Viau render obvious claim 1. Additionally, Weissman teaches wherein the dry platelet lysate material is ground, so as to obtain a powder (par 0178).
Regarding claim 7, the combined teachings of Muraglia, Weissman and Viau render obvious claim 1. Additionally, Weissman teaches wherein a liquid is added to the dry platelet lysate material, so as to obtain a reconstituted platelet lysate material (par 0176, 0180). This is supported by Muraglia as seen by describing after freeze-drying and gamma radiation the product is mixed with water, “After its reconstitution with water, the freeze-dried PL was used in the cell culture medium.” (p 2, col 2).
Regarding claim 8, the combined teachings of Muraglia, Weissman and Viau render obvious claim 1. Additionally, Weissman teaches wherein the blood platelets are obtained or isolated from a thrombocyte concentrate (“The platelet-enriched fractions can be, for example, separated from units of whole blood, from blood fractions and/or from plasma fractions. The platelet-enriched fractions can be obtained from aphaeresis donations.” (par 0137) and subsequently lysed by a freeze-thaw process (“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 (e.g., thrombocytes) enriched fractions” (par 0141)).
Claim 21 is rejected based on the limitations being identical to those found in claims 1 and 2 which are rejected above, in particular Muraglia teaches using gamma irradiation on dry platelet lysate, Weissman teaches using multiple, different inactivation treatments that include UV and dry heat, and Viau teaches using UV-C irradiation to obtain viral inactivated platelet lysates.
Regarding claims 22 and 23, both dependent on claim 21, the combined teachings of Muraglia, Weissman and Viau render obvious claim 21. Additionally, Weissman in view of Muraglia teaches the material produced comprises 5-15 % blood platelet lysate (“After its reconstitution with water, the freeze-dried PL was used in the cell culture medium at a final 5% concentration of different preparations containing variable concentrations of the original platelet content” (Methods, “Platelet lysate preparation”)). Furthermore, Viau teaches the treated platelet lysate at a range from 2 to 15% for cell cultivation (“BM-hMSC proliferation determination”).
Regarding claim 24, dependent on claim 21, the combined teachings of Muraglia, Weissman and Viau render obvious claim 21. Additionally, Muraglia and Viau teach the cultivation of mesenchymal stem cells with the treated platelet lysate material (Muraglia, p2, col 2; Viau, abstract).
Response to Applicants’ Arguments as they apply to rejection of claims 1, 4-8 under 35 USC § 103
Starting on page 6 of the remarks filed on April 23, 2025, Applicants essentially argue the following:
In relation to claim 1, Applicants’ argue that Weissman teaches using two orthogonal treatments, and that different irradiation treatments are not considered orthogonal treatments, or rather at least two different and independent treatments for inactivating viruses (par 0084).
Applicant further submits that it would not have been obvious to one of ordinary skill in the art to have modified Weissman's method by freeze drying the PL prior to a viral inactivation treatment.
In response to these arguments they have been fully considered but are not persuasive due to the following reasons:
Regarding the first presented argument, Weissman teaches using different viral inactivation treatments so as to provide a virus-free or at least virus-reduced platelet lysate material that encompasses pasteurization [heat inactivation], Solvent/Detergent (S/D), nanofiltration, Low pH treatment, UV irradiation and Sodium thiocyanate treatment.” (par 0084;par 0064-66). The reference states the treatments are to be different and independent, and in view of this Muraglia teaches a different and independent treatment of gamma irradiation for platelet lysates. Furthermore, the new rejection also supports the use of UV irradiation for viral inactivation of PL as seen by Viau using such treatment to then be used in cell culturing. Altogether, it would remain obvious to use different forms of irradiation in view of such methods being taught in the prior art, and there being support for using different treatments to obtain viral inactivated-PL for cell cultivation.
Regarding the second presented argument, the Muraglia reference makes it clear that freeze-dried platelet lysate is able to be virally inactivated by gamma irradiation, and remains capable of supporting cell cultivation, e.g. mesenchymal stem cells. Muraglia clearly teaches the freeze drying and irradiation of platelet lysate, “The supernatant PL was recovered and distributed into 5-ml cryotubes and frozen at -80 ̊C. PL was freeze-dried and gamma irradiated according to the same procedure used for the PRP. After its reconstitution with water, the freeze-dried PL was used in the cell culture medium at a final 5% concentration of different preparations containing variable concentrations of the original platelet content.” (p 2, Sec. “Platelet lysate preparation”). Moreover, Muraglia describes that increased radiation dosages impacted colony number and size, and then suggested limiting the use of the gamma irradiation to dosages from 0.1 to 1 KGy, in which the remainder of the tests were conducted at 0.1 KGy (p 5, col 1).
Therefore, the process of using viral-inactivation treatments on dried platelet lysate was known prior to filing date of the claimed invention, and moreover the treatment of similarly using irradiation, but rather UV treatment as taught both by Weissman and Viau, on dried platelet lysate would have a reasonable expectation of success in obtaining a viral inactivated product based on it being well-known to efficiently inactivate viruses for liquid platelets. Furthermore, Applicants have not provided any evidence that UV irradiation could not sterilize a dried/lyophilized platelet lysate material as well as the hydrated form.
New Grounds of Rejections
Claim Rejections - 35 USC § 112
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.
Claim 7 is 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 applicant regards as the invention.
Claim 7 is indefinite at the recitation of “wherein a liquid is added to the dry platelet lysate material, so as to obtain a reconstituted platelet lysate material.” because it is unclear if the “dry platelet lysate material” is in reference to the “virus-free or at least virus-reduced dry platelet lysate material” or rather the material prior to this product. Appropriate correction is required.
Conclusion
Claims 1-2, 5-8 and 21-24 are rejected. No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MICHAEL A RIGA whose telephone number is (571)270-0984. The examiner can normally be reached Monday-Friday (8AM-6PM).
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Maria G Leavitt can be reached at (571) 272-1085. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/MICHAEL ANGELO RIGA/Examiner, Art Unit 1634
/MARIA G LEAVITT/Supervisory Patent Examiner, Art Unit 1634