DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
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 1-15 were previously pending.
Receipt is acknowledged of the claim amendments submitted on 04 February, 2026. Claims 1, 3-7, and 10-15 are amended. Claims 2, and 9 are cancelled. Claims 16-20 are newly added.
Therefore, claims 1, 3-8, and 10-20 are pending and are the subject of the present Official Action.
Priority
The present Application claims priority to United States Provisional Application No. 63/300,355 filed 18 January, 2022. Acknowledgement is made of Applicant’s claim for priority.
The earliest possible priority for the instant application is 18 January, 2022.
Drawings
The drawings submitted on 10 January, 2023 are accepted by the Examiner.
Withdrawn Objections/Rejections in view of Applicant’s Amendments/Arguments
Claim Objections
The objection to claims 4, 11, and 15 because the claims improperly use the term “an” to refer to a noun beginning with a consonant is withdrawn in view of Applicant’s amendments to the claims.
The objection to claim 15 because the claim appears to mis-spell the words concentration and dose is withdrawn in view of Applicant’s amendments to the claims.
Maintained Rejections/Objections in view of Applicant’s Amendments/Arguments
Claim Rejections - 35 USC § 112
Claims 1, 3-8, and 10-15 remain rejected and claims 16-20 are newly 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. This rejection has been modified as necessitated by Applicant’s amendments to the claims.
Claims 1 and 15 recite “wherein the solutions were derived from a plurality of donors”. This language is unclear because it is unclear what steps are encompassed by the term “derived” nor what steps a person having ordinary skill in the art would have to take to avoid falling within the scope of the term “derived”. Although the claims set forth providing a leukoreduction system chamber comprising a solution…wherein the solution was produced during a platelet apheresis procedure performed on a donor, this does not suffice to clarify the term “derived from” for “a plurality of solutions” derived from “a plurality of donors” because these are distinct antecedents setting forth distinct claim limitations. Even where providing a leukoreduction system chamber comprising a solution…wherein the solution was produced during a platelet apheresis procedure performed on a donor is recited, it is not in connection with the term “derived from” so it cannot be determined that Applicant intends “derived from” to encompass such steps. Accordingly, a person having ordinary skill in the art would not be apprised of the scope of the patent protections sought.
Claims 1 and 15 separately recite “a solution” and “a donor” in the first step of each claim followed by a recitation of “a plurality of solutions” and “a plurality of donors” in the next step of combining. It is unclear whether “a plurality of solutions” is intended to refer back to “a solution” as recited just as it is unclear whether “a plurality of donors” is intended to refer back to “a donor”. Accordingly, it is unclear whether Applicant intends the scope of claims 1 and 15 to encompass a plurality of solutions and a plurality of donors wherein a solution and a donor within each plurality are the first donor and solution recited (thereby limiting the pluralities to require a leukoreduction system chamber and platelet apheresis) or whether the pluralities recited are instead intended to be distinct solutions and donors from those previously mentioned. This issue is compounded by Applicant’s referring to each with the definite article “a” which produces an inference that they are intended to be distinct. This rejection can be remedied by instead reciting the respective pluralities in the step of “providing” to be referenced by the step of “combining”. Care should be taken to avoid introducing new antecedent issues in the dependent claims.
Claim 1 and 15 now recite “configured” in place of “sufficient”. It is unclear how one configures a radiation dose to inhibit cell division and growth and to maintain biological activity to fall within the scope of the instant claims. Accordingly, a person having ordinary skill in the art would not be apprised of the scope of the patent protection sought.
Claims 1 and 15 are independent claims. All other claims depend from claim 1 directly or indirectly. Therefore, claims 3-8, and 10-20 are further rejected for their dependency on a rejected base claim.
Claim Rejections - 35 USC § 103
Claims 1, 3-8, and 10-15 remain rejected and new claims 16-20 are newly rejected under 35 U.S.C. 103 as being unpatentable over Luhm et al. Journal of hematotherapy & stem cell research 11.4 (2002): 651-657. (hereinafter “Luhm”) in view of Yang et al. BMC immunology 17.1 (2016): 6. (hereinafter “Yang”), Abreu, et al. Journal of clinical apheresis 11.1 (1996): 27-29, hereinafter “Abreu”, and Kim, et al. (2007): 4912-4912, hereinafter “Kim”. This rejection has been modified as necessitated by Applicant’s amendments to the claims.
Regarding claim 1, Luhm discloses a method of generating feeder cells (Luhm, page 652, “Generation of feeder cells” heading). Luhm discloses that mononuclear cells (MNCs) were harvested from buffy coats by separating the MNCs from contaminating cells via density gradient centrifugation (Luhm, page 652, “MATERIALS AND METHODS” heading). It is noted that the density gradient centrifugation to separate MNCs from contaminating cells is encompassed by the instant step of “isolating”. Luhm also discloses that the MNCs were harvested by apheresis prior to isolating the MNCs and that the apheresis was performed on a Baxter CS 3000 unit (Luhm, page 652, “MATERIALS AND METHODS” heading). Luhm also discloses that the method comprises washing the MNCs three times with PBS following isolation and irradiating the MNCs with 70 Gy of γ-radiation (Luhm, page 652, “Generation of feeder cells” heading).
Luhm does not teach the use of leukoreduction system chambers, or the combining a plurality of the blood material as required by instant claim 1. Luhm also does not explicitly teach that 70 Gy of γ-radiation is sufficient to inhibit cell division and growth while maintaining biological activity.
Yang teaches a method for isolating peripheral blood mononuclear cells (PBMCs) from whole blood wherein the whole blood is collected from 10 different donors and pooled to create a homogenate mixture prior to isolation of the PBMCs (Yang, page 3, second and third paragraphs). Yang teaches the need to standardize all aspects of PBMC isolation and storage because blood is often collected, processed, and cryopreserved at different clinical sites (Yang, pages 1-2, “Background”, first paragraph).
Thus, a person having ordinary skill in the art would have been motivated to pool whole blood samples prior to isolating MNCs to produce a homogenous and more standardized MNC product. Further, the level of ordinary skill in the art of cellular and molecular biology encompasses pooling samples to create a homogenous and more standardized product.
It is noted that 70 Gy is equal to 7,000 rad. According to instant claim 13, a radiation dose from 2,500 to 75,000 rads is an amount sufficient to inhibit cell division and growth while maintaining biological activity. Accordingly, the method of Luhm which comprises irradiating MNCs with 70 Gy γ-radiation is encompassed by instant claim 1.
Abreu teaches that the CS-3000 instrument can be used with leukocyte reduction chambers to better separate leukocytes (including MNCs) from platelets (Abreu, Abstract, page 27, “MATERIALS AND METHODS” heading). Kim teaches that leukocyte reduction chambers are a valuable and convenient source of viable human MNCs and that it could replace standard buffy coat preparations (Kim, whole paragraph). Thus, a person having ordinary skill in the art would have understood from the teachings of Abreu and Kim that they could have used leukoreduction chambers to have derived the MNCs in the method of Luhm prior to centrifugation and they would have been motivated to do so to improve the method of Luhm by rendering it more convenient.
Therefore, it would have been prima facie obvious to a person having ordinary skill in the art before the effective filing date of the claimed invention to have pooled multiple of the buffy coat samples of Luhm as taught by Yang and to have used a leukoreduction chamber as taught by Abreu and Kim prior to MNC isolation and irradiation and to have arrived at the invention claimed in instant claim 1 with a reasonable expectation of success because they would have been motivated to do so to produce a homogenous and more standardized feeder cell product as well as to improve the convenience of the method of Luhm. There would have been areasonable expectation of success in combining the methods of Luhm, Yang, Abreu, and Kim insofar as all teach the isolation of specific blood components and Kim suggests to replace standard buffy coat preparations with leukoreduction preparation for the purification of MNCs.
Regarding instant claims 3 and 10, the method of Luhm comprises adding phosphate-buffered saline (PBS) to the buffy coats prior to isolation of the MNCs (Luhm, page 652, “Density gradient centrifugation” heading).
Regarding instant claims 4 and 11, Luhm isolated the MNCs by density gradient centrifugation and collection of distinct fractions afterward wherein one of those fractions contains MNCs (Luhm, page 652, “Density gradient centrifugation” heading). Note that Luhm states, “MNC were derived from buffy coats and separated from contaminating cells by a density centrifugation step as described above” ( Luhm, page 652, “Generation of feeder cells” heading), rendering obvious the step of “centrifuging the heterogeneous material” to produce an MNCs layer and one or more other layers. The fractions of Luhm are encompassed by the broadest reasonable interpretation of the claim term “Layer”.
Regarding instant claims 5 and 12, the method of Luhm uses a Ficoll solution for the density gradient to separate the MNCs. The broadest reasonable interpretation of the claim term “density gradient medium” encompasses Ficoll solution.
Regarding instant claim 6, the method of Luhm comprises washing the MNCs three times before irradiating them. Luhm also teaches the adjusting of the cells to 1x10^6 cells/ml and culturing for 3-5 days prior to washing (Luhm, page 652, “Generation of Feeder Cells”). It is noted that washing cells necessarily adjusts their concentration. Regarding the particular concentration of 1-4 x 10^8 recited: 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. "[W]here 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." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). After 3-5 days of culture, Luhm need only reduce the volume of the solution through the washing step to increase the cell concentration to the level claimed. The level of ordinary skill in the art of cellular and molecular biology encompasses adjusting cell concentrations in between the steps of any given protocol to produce reproducible results.
Regarding instant claim 7, the washing of Luhm comprises washing with PBS (Luhm, page 652, “Density gradient centrifugation” heading).
Regarding instant claim 8, the washing of Luhm is repeated twice for a total of three washes.
Regarding instant claim 13, the radiation dose of Luhm is 70 Gy which is equal to 7,000 rad.
Regarding instant claim 14, Luhm also does not teach storing the feeder cells at a temperature between -20 degrees Celsius to -90 degrees Celsius.
Yang teaches that PBMCs are regularly cryopreserved (Yage, page 1, “Background”). Yang also teaches that use of the PBMCs is frequently done in batches and to enable this, PBMCs are often cryopreserved and stored at ultra-low temperatures until they are used (Yang, pages 1-2, “Background” heading, first paragraph). Yang also teaches that PBMCs can be stored up to 1.5 years at -70/-80 degrees Celsius (Yang, page 2, third paragraph). Thus, a person having ordinary skill in the art would understand from the teachings of Yang that MNCs can be stored at -70/-80 degrees Celsius to enable long-term use and they would have been motivated to do so to store the feeder cells of Luhm for later use.
Regarding instant claim 15, the combined teachings of Luhm and Yang teach all claim limitations which have been mapped and discussed above.
Regarding new claims 16 and 20, Yang teaches that DMSO cryoprotectants are routinely used for the cryopreservation of PBMCs and specifically teaches to add DMSO as a cryoprotectant prior to cryopreservation (Yang, page 10, first full paragraph, page 3, “Control-rate freezing).
Regarding new claim 17, the buffer solutions of Luhm are phosphate buffered solutions.
Regarding new claim 18, Luhm teaches to add 400mL PBS to a 600mL bag containing the apheresis product (Luhm, “MATERIALS AND METHODS”). Thus, maximum ratio that Luhm could teach is a 2:1 ratio of PBS to apheresis product. 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. "[W]here 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." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). As there is no evidence indicating that the ratio of PBS is critical, it would have been obvious to have discovered the optimal or workable ranges by routine experimentation.
Regarding new claim 19, Yang teaches to use a Ficoll-Paque solution for density gradient centrifugation of the MNCs (Yage, page 3, “PBMC isolation”).
Response to Arguments
Applicant argues against the prima facie obviousness of the pending claims by arguing that Luhm and Yang do not teach the leukoreduction system chamber in amended claim 1 (Remarks, at page 9). This argument has been fully considered but has not been found persuasive because claim 1 has been amended to recite the leukoreduction system chambers, and Abreu and Kim have been provided to meet the amended claim language. Kim teaches that leukocyte reduction chambers are a valuable and convenient source of viable human MNCs and that it could replace standard buffy coat preparations (Kim, whole paragraph) and Abreu teaches that the apheresis system of Luhm can be used with leukoreduction chambers. Accordingly, Applicant’s arguments have been fully considered but have not been found to be persuasive.
Conclusion
No claim is 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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/BRENDAN THOMAS TINSLEY/Examiner, Art Unit 1634
/MARIA G LEAVITT/Supervisory Patent Examiner, Art Unit 1634
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