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 .
Continued Examination Under 37 CFR 1.114
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 11/03/2025 has been entered.
Claim 68 has been amended. Claims 82-83, 120-121 and 123 have been newly canceled and claims 125-126 have been newly added.
Claims 68-77, 79, 81, and 124-126 are currently pending and have been examined on their merits.
Rejections and/or objections not reiterated from previous office actions are hereby withdrawn due to amendment. The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application.
Claim Interpretation
Regarding claim 68, the phrase “wherein the method results in the pathogen-inactivated platelet composition after step (d) comprising 5 µM or less of PIC” is interpreted as indicating that at some point after the step of subjecting the admixture to light and yielding platelet composition that has been inactivated for pathogens that the PIC level will become 5 µM or less. This phrase is not interpreted as requiring the exclusion of further processing steps to remove residual PIC after step (d).
Regarding claim 68, the phrase “wherein the method results in a pathogen-activated platelet composition that is suitable for infusion into a subject without further processing to remove residual PIC or photoproducts thereof” is interpreted as indicating that when the last step of the method occurs (step d) that the product produced at this point is suitable for infusion into a subject. This phrase is not interpreted as requiring the exclusion of further processing steps to remove residual PIC after step d, only that the product at this point is suitable for infusion if needed or desired.
Support for these interpretations is found in Applicant’s Specification at pages 49-52 paragraphs 111-114 for example. The only instance wherein Applicant discloses wherein their method is able to achieve a residual PIC of 5 µM or less without a step for PIC removal is when an incubation step is included and even then, it is only when the starting PIC concentration used is 30 µM or 15 µM (see Table 10 page 76).
Therefore, the only embodiment supported by Applicant’s Specification for achieving residual PIC of 5 µM or less with the claimed PIC concentration range is when steps for further removal of residual PIC are included.
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.
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.
Claim(s) 68-77, 79, 81 and 124-126 are rejected under 35 U.S.C. 103 as being unpatentable over Greenman et al (WO 2016/115535-from IDS filed 05/06/2024) in view of Lin et al (US 5,709,991-from IDS filed 05/06/2024), Moore et al (US 7,445,756-previously cited) and Wollowitz et al (US 5,593,823-from IDS filed 05/06/2024).
Regarding claim 68-77, 81 and 125-126, Greenman teach a method of providing a platelet product (Title). The platelets are treated to a photochemical treatment that includes combining platelets with a PAS (platelet additive solution) and a psoralen compound, such as amotosalen, and subjecting the admixture to light sufficient to photochemically inactivate a pathogen if present (pages 38-39, para 73). A variety of desired volumes and platelet amounts may be achieved based on the number of platelet components pooled and the pooled platelet components can subsequently be split into two or more platelet products (transfusion ready platelet product) each comprising a desired amount of platelets, such as, an amount of platelets for a therapeutic dose (page 42 para 80). Pooled platelet products (two or more platelet components) and such pooling may provide a platelet product that comprises at least 3 platelet components (page 42 para 80).
Greenman teach wherein the reduction in a particular active pathogen is at least about 1 log (pages 35-36 para 70) and that “it may be desirable to remove the psoralen” (page 39 para 73), but removal of the psoralen is not necessarily required (due to the use of the term “may”). Therefore, embodiments that do not include a step for removing the psoralen are deemed to be in a form suitable for infusion into a subject baring evidence to the contrary. The claims do not require the exclusion of a PIC removal step or a transfer step, only that the platelet product be in a form suitable for infusion into a subject without relying on these steps.
Greenman do not specifically describe using a first container, second container and third container each containing different volumes of solution comprising a PAS and a PIC and then selecting the containing for admixing the platelets and subjection to light as claimed. Greenman do indicate that their method can be performed in any suitable order unless otherwise indicated (page 69-70, para 125).
Lin teach a method of psoralen inactivation of microorganisms for photo-decontamination in platelet preparations (Title and abstract). Lin teach that a phosphate buffered aqueous salt solution, a psoralen and platelets may be provided in any order (column 3, column 5). Lin teach that devices capable of treating a plurality of blood product containers can be provided for simultaneous treatment and by accepting commonly used commercially available blood bags that allow for convenient processing of large numbers of samples (columns 9-10).
Moore teach systems and methods for treating biological fluid with light (abstract). The sizes and internal volumes of the containers may vary depending on the biological fluid being processed (column 14). The processing set is used in or as part of a pathogen inactivation treatment with a photochemical agent, such as a psoralen, which is mixed with the biological fluid, such as blood platelets, and includes containers suitable for light treatment (columns 14-15).
One of ordinary skill in the art would have been motivated to include a container system that includes at least 3 containers for the preparation of different platelets products with varying volumes and doses in each container in the method of Greenman because Greenman indicate that a variety of desired volumes and platelet amounts may be achieved based on the number of platelet components pooled and the pooled platelet components can subsequently be split into two or more platelet products (transfusion ready platelet product) each comprising a desired amount of platelets, such as, an amount of platelets for a therapeutic dose (page 42 para 80). Adding the PAS and the PIC first to each container would have been motivated by the teaching of Lin which specifically indicates that these components can be added to containers in any order. One of ordinary skill in the art would have been motivated to vary the volumes in each container to include various does amounts of solutions and platelets as Moore indicates that sizes and internal volumes of the containers may vary depending on the biological fluid being processed (column 14) and Greenman also indicate that a variety of desired volumes and therapeutic dose amounts can be used as well in their method. One of ordinary skill in the art would have had a reasonable expectation of success because Greenman, Lin and Moore are all drawn to the photo-decontamination treatments of platelet products with psoralen solutions and light.
Greenman teach wherein the psoralen is amotosalen at a concentration of 120-193 µM (page 39 para 73) and wherein the reduction in a particular active pathogen is at least about 1 log (pages 35-36 para 70) and suggest removal of the psoralen after treatment is an option and that such removal methods are known in the art (page 39 para 73). Greenman do not indicate that the result of pathogen inactivation is contingent on the use of a CAD (compound adsorption device) and thus an option wherein the removal of the psoralen (PIC) is accomplished without a CAD is included as a suitable embodiment. One of ordinary skill in the art would have been motivated with a reasonable expectation of success to remove the psoralen (PIC) after light treatment to levels as low as possible, such as zero (less than 5 µM) because Greenman teach that this is desirable and that methods to remove psoralen are known in the art.
Greenman do not teach wherein their pathogen activation concentration is in a range of about 30-90 µM or 50-75 µM.
With regard to the concentrations of the pathogen inactivation compound (PIC) in the platelet composition, 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) (MPEP 2144.05).
The selection of specific concentrations clearly would have been a routine matter of optimization and experimentation on the part of the artisan of ordinary skill, said artisan recognizing that the viability of the platelets and degree of pathogen inactivation would have been affected by these concentrations.
Wollowitz teach methods for inactivating pathogens in blood products using photoinactivation of psoralens, such as S-59 (amotosalen), and suggest that psoralen concentrations of 10-150 µM, specifically 64 µM, are suitable concentrations for pathogen inactivation of platelets (column 3 line 38-column 4 line 5, column 40 lines 62-67, columns 41-42, Table 10, Table 11). The use of synthetic media comprising a buffered saline solution reduces harm to blood products and permits the use of much lower concentrations of photoactivation compounds (column 19, lines 20-27). Wollowitz teach that the providing of the individual components (psoralen, PAS and platelets) in the first step of the method can be in any order (column 3 lines 40-55). Wollowitz also teach and suggest the use of a plurality of sample containers in their method (column 8 line 61-column 9 line 17).
Lin teach that when it comes to the use of psoralens for pathogen inactivation that much lower concentrations than previously employed can be used and that this comes from the understanding that it is not essential that inactivation be complete. That is, partial inactivation will be adequate as long as the viable portion is unable to grow to levels sufficient to cause disease (column 7). This would have provided additional motivation and a reasonable expectation of success to use lower concentrations of the pathogen inactivation compound in the method of Greenman.
One of ordinary skill in the art would have also been motivated to use a lower concentration of a psoralen, such as S-59, in the method of Greenman because Wollowitz teach and suggest a lower psoralen concentration range is desirable (column 19 lines 20-27) and disclose a range of 10-150 uM that encompasses the claimed ranges of 30-90 uM and 50-75 uM, and specifically disclose a concentration of 64 uM which falls within the claimed ranges and also rendering the claimed ranges obvious choices for the optimization of a psoralen used to inactivate pathogens in a platelet composition and this would allow for the benefit of less residual psoralen after pathogen inactivation. One of ordinary skill in the art would have had a reasonable expectation of success because Greenman and Wollowitz are drawn to photo-decontamination treatments of platelet products with psoralen solutions and light.
Regarding claim 79, Greenman teach transferring the platelet composition after treatment to a suitable storage container (page 50 para 94).
Regarding claim 124, Greenman teach wherein the platelet composition comprises at least 2 X 1011 platelets (page 39 para 73).
Therefore, the combined teachings of Greenman et al, Lin et al, Moore et al and Wollowitz et al render obvious Applicant’s invention as claimed.
Response to Arguments
Applicant's arguments filed 11/03/2025 have been fully considered but they are not persuasive.
A. Applicant argues that the combination of Greenman, Lin and Moore fails to teach or suggest an admixture of PAS, PIC, and a preparation of platelets that comprises the PIC at a concentration of about 30-90 uM.
Applicant argues that Greenman does not disclose the claimed range that has been added to the newly amended claim 68 and instead discloses a higher concentration range for the PIC.
This is not found persuasive. The previous obviousness rejection has been modified to include the teachings of the Wollowitz reference which discloses a suitable concentration range for psoralen (PIC) which does encompass Applicant’s claimed ranges for the PIC.
B. Applicant argues that the combination of Greenman, Lin and Moore fails to teach or suggest a method resulting in a platelet composition that comprises 5 uM or less of PIC after photochemical pathogen inactivation without further processing.
Applicant argues that the Examiner has alleged that a person of ordinary skill in the art would have been motivated with a reasonable expectation of success to remove the psoralen (PIC) after light treatment to levels as low as possible, such as zero, less than 5 uM, because Greenman teach that this is desirable and that method to remove psoralen are known in the art in the last Office Action at page 7. Applicant argues that the newly amended claims now require that only the steps of providing, selecting, admixing, and subjecting are specified are performed resulting in a pathogen -inactivated platelet composition that comprises 5 uM or less of PIC or photoproducts thereof and without invoking any un-recited processing step related to PIC removal. Applicant also argues that Greenman does not disclose any specific residual PIC concentration less than 5 uM as claimed without further processing. Applicant asserts that the combination of references with Greenman do not recite these limitations as well.
This is not found persuasive. As described above, the claims are interpreted as not requiring the exclusion of a PIC removal step, but that the platelet product produced after step (d) be suitable for infusion which the prior art references states that it is as PIC removal is disclosed as optional.
In addition, the only instance wherein Applicant discloses wherein their method is able to achieve a residual PIC of 5 µM or less without a step for PIC removal is when an incubation step is included and even then, it is only when the starting PIC concentration used is 30 µM or 15 µM (see Table 10 page 76). Therefore, the only embodiment supported by Applicant’s Specification for achieving residual PIC of 5 µM or less with the claimed PIC concentration range is when steps for further removal of residual PIC are included.
C. Applicant argues that the combination of Greenman, Lin and Moore fails to teach or suggest selecting a container containing a solution comprising a PAS and a PIC for use in preparing a platelet composition.
Applicant argues that the statement cited by the Examiner in Greenman (paragraph 125) stating that “[a]ll methods described herein can be performed in any suitable order unless otherwise indicated and herein or otherwise clearly contradicted by context” does not apply to combining PAS, PIC and platelets to perform method steps in any suitable order. Applicant asserts that there is no teaching or suggestion in Greenman that mixing the PAS and PIC before the addition of platelets would be considered a suitable order by one of ordinary skill in the art at the time the instant application was filed. Applicant asserts that the only motivation for changing the order of the steps as suggested by the examiner is hindsight reasoning based on the pending claims.
This is not found persuasive. In response to applicant's argument that the examiner's conclusion of obviousness is based upon improper hindsight reasoning, it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971).
In the current instance, Greenman discloses that the order of all their methods can be modified and this is sufficient for motivation and reasonable expectation of success to change the order that the platelets, PIC and PAS are added together prior to light exposure. However, there is additional motivation from the other cited references as well. Wollowitz specifically states that the providing of the individual components (psoralen, PAS and platelets) in the first step of the method can be in any order (column 3 lines 40-55).
Applicant argues that there are other disclosures in Greenman that illustrate how providing a solution of PAS and PIC before the addition of platelets is contradicted by context. Applicant points to paragraphs 73, 78 and 79 as examples wherein a platelet unit is described prior to addition of amotosalen, wherein the PAS is added to buffy coat prior to isolation of platelets, storage and further processing that can include pathogen inactivation treatment and wherein PAS is added to isolated PRP-derived platelet components before storage and further processing that can include pathogen inactivation treatment. Applicant asserts that there is no teaching or suggestion that the generic statement related to the performance of method steps could be applied to the order of combining PAS, PIC and platelets while there are multiple contexts in which PAS is added to platelets before the introduction of a PIC. Applicant asserts that the skilled person would not seek to modify the methods of Greenman to provide a solution of PAS and PIC before contacting the solution of PAS and PIC with a preparation of platelets based on the disclosures of Lin as cited by the Examiner.
This is not found persuasive. Greenman discloses that the order of all their methods can be modified and this is sufficient for motivation and reasonable expectation of success to change the order that the platelets, PIC and PAS are added together prior to light exposure. However, there is additional motivation from the other cited references as well. Wollowitz specifically states that the providing of the individual components (psoralen, PAS and platelets) in the first step of the method can be in any order (column 3 lines 40-55).
Applicant argues that the concentration of PIC at about 30 µM to about 90 µM in the admixture of step (c) as recited in the amended claim 68 is not somewhat narrower than the range disclosed by Hei. Applicant asserts that the concentration range of 0.1 µM to 250 µM disclosed by Hei encompasses a span of three orders of magnitude whereas the claimed range encompasses only a single order of magnitude and thus the range disclosed by Hei is too broad to render obvious the claimed range despite the teaching of MPEO 2144.05(I).
This is not found persuasive. First, MPEP 2144.05 (III)(D) which Applicant relies upon to disprove that a broad range can render obvious a narrower range, indicates that this can occur where applicant establishes that the prior art disclosure of the variable is within a range that is so broad in light of the dissimilar characteristics of the members of the range as to not invite optimization by one of skill in art can be a factor weighing against obviousness. Yet, Applicant has not discussed any dissimilar characteristics of the members of the group and as such has not provided sufficient evidence to establish that routine optimization of the disclosed concentration range of psoralens would not render obvious the claimed range. Second, the obviousness rejection does not rely on the teaching of the Hei reference and now includes the teaching of Wollowitz which disclose a concentration much closer to the claimed range as described above as well as a specific concentration of a psoralen that falls within Applicant’s claimed range.
Applicant argues that the range of 0.1 to 250 µM PIC disclosed by Hei is so broad as to not invite optimization by the skilled person and point to MPEP 2144.05(III)(D) for support for this assertion. Applicant asserts that a mere motivation to use a lower concentration of a psoralen as alleged by the Examiner would not sufficient guidance since the lower end of the claimed range is still much greater (300 fold greater) than the lower end of the 0.1 µM as taught by Hei. Applicant asserts that Hei fails to remedy the deficiencies of Greenman, Lin and Moore.
This is not found persuasive. The obviousness rejection does not rely on the teaching of the Hei reference and now includes the teaching of Wollowitz which disclose a concentration much closer to the claimed range as described above as well as a specific concentration of a psoralen that falls within Applicant’s claimed range.
In view of the foregoing, when all of the evidence is considered, the totality of the rebuttal evidence of nonobviousness fails to outweigh the evidence of obviousness.
Conclusion
No claims are allowed.
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
McBurney et al., “Storage Solutions Containing Photosensitizer for Inactivation of Biological Contaminants”, US 6,548,241 B1.
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LAURA J. SCHUBERG
Primary Examiner
Art Unit 1631
/LAURA SCHUBERG/Primary Examiner, Art Unit 1631