DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 12/22/2025 has been entered.
Claim 61 has been amended. No claims have been newly added or newly canceled.
Claims 51-64 are currently pending.
Rejections and/or objections not reiterated from previous office actions are hereby withdrawn due to amendment.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
Claim 51 has been amended to include the absence of “an additional molecular cocktail comprising cytokines”. This is interpreted as in the absence of an addition of exogenous cytokines to the method. This has support in original claim 7 and in the Specification at page 3 lines 25-30.
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 pre-AIA 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter 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 pre-AIA 35 U.S.C. 103(a) 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 under pre-AIA 35 U.S.C. 103(a), the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were made absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and invention dates of each claim that was not commonly owned at the time a later invention was made in order for the examiner to consider the applicability of pre-AIA 35 U.S.C. 103(c) and potential pre-AIA 35 U.S.C. 102(e), (f) or (g) prior art under pre-AIA 35 U.S.C. 103(a).
Claims 51-64 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Richard Leslie Edelson (WO 2011/137365-previously cited) in view of Mihret et al (BMC Research 2011-previously cited), Ebner et al (Immunobiology 1997/98-previously cited) and Cohen et al (Blood 2006-from IDS filed 10/04/2023).
Regarding claims 51-58 and 64, Edelson ‘365 discloses a method of production of immune enhancing (immuno-stimulatory) dendritic cells (DCs) in an extracorporeal photopheresis (ECP) device (page 24 claim 1 and page 11 [0041]). A shear force (physical force) is applied to the monocytes contained within the subject's blood sample (page 25 claim 7). Flow rate is adjusted for each blood component (tunable flow chamber) (page 4 [0014]-[0016]). A photoactivatable agent, such as 8-MOP, is taught to be optional (page 5 [0018], page 12 [0042], page 13 [0048]) and thus an embodiment wherein photoactivatable DNA crosslinking agents are absent is included as an obvious option. To generate immunizing DCs the monocytes are not treated with psoralen and UV light (page 12 [0042]). Edelson teach that the activated monocytes produce natural cytokines which aid in the differentiation of the monocytes into dendritic cells and any additional cytokine addition is optional, thus not required and thus an embodiment wherein exogenous cytokines are absent is included as an obvious option (page 18, [0061]). Edelson teach that the dendritic cells created by their method provide a relatively narrow age profile (synchronized) an enhanced number of dendritic cells capable of phagocytizing (engulfing) apoptotic disease effector agents and subsequently presenting antigens from those disease effector agents for use in immunotherapeutic treatment (page 17-18 [0059]). The cells are autologous to the subject that they have been obtained from. The term disease effector agents refers to cells and their antigens including cancer cells, and microbial peptides that are viral, bacterial or fungal (page 15-16, [0053]-[[0055)).
Since the blood sample is subjected to the physical force as required by the claims, the dendritic cells and their molecular markers generated by this treatment of physical force and activated platelets (see below) are deemed to be inherently present and thus identifiable. If this were not the case it would appear that claim 51 would have to be missing essential method steps required for the claimed molecular markers to be expressed.
Regarding claims 51, 57-63, Edelson teach that their method may comprise separating the blood sample into three components (plasma, platelets and buffy coat which allow for blood samples excluding the other components) before applying to a device, coating the plastic channels with plasma proteins, pumping the platelet fraction into the plastic channels so that the platelets adhere to and are activated by the plasma proteins (fibronectin, fibrinogen) and finally pumping the monocyte fraction into the device thereby effecting differentiation of the monocytes into DCs (pages 12-13 [0045]- [0047]).
Edelson do not teach a step for determining the expression levels of at least ICAM-1 and PLAUR on immune-stimulatory autologous antigen presenting cells or dendritic cells wherein increased expression of at least ICAM-1 and PLAUR is taken as inducing differentiation of monocytes into immune-stimulatory autologous anti-presenting cells or dendritic cells.
Mihret teach that when dendritic cells are mature and activated that they express molecular markers CD54 (ICAM1), CD83 and CD86 (abstract, page 2 of 7, column 1).
Ebner teach that mature dendritic cells express CD83, CD86 (abstract) and that expression of CD87 (PLAUR) is found on both immature and mature dendritic cells and crucial for cell function (page 579, last paragraph).
One of ordinary skill in the art would have been motivated to observe the surface markers characteristic of mature dendritic cells in the method of Edelson ‘365 because Mihret and Ebner indicate that this ensures that the desired mature dendritic cells are obtained as the product. One of ordinary skill in the art would have had a reasonable expectation of success because both Edelson ‘365, Mihret and Ebner are drawn to obtaining dendritic cells from in vitro differentiated hematopoietic precursor cells.
Edelson '365 do not specifically teach determining the expression of GILZ on their dendritic cells.
Cohen teach that GILZ expression is lost during dendritic maturation (page 2039, Results) and that a simple explanation for the effect of GILZ on dendritic cell (DC) function would be that it prevents dendritic cell (DC) maturation (page 2043, end of column 1).
Therefore, one of ordinary skill in the art would have been motivated to determine GILZ expression in the dendritic cells of Edelson '365 in order to ensure that there is no increased expression so that the desired mature immune-stimulatory dendritic cell is obtained because Cohen suggest that GILZ expression is lost during maturation and that GILZ expression would prevent DC maturation. One of ordinary skill in the art would have had a reasonable expectation of success because Edelson '365 and Cohen are both isolating mature immune-stimulatory dendritic cells for future use and research.
Therefore, the combined teaching of Edelson ‘365, Cohen et al, Mihret et al and Ebner et al render obvious Applicant’s invention as claimed.
Response to Arguments
Applicant’s arguments, see page 1 line 8, filed 12/22/2025, with respect to the rejection(s) of claim(s) 51-64 under 35 USC 103a over Edelson in view of Mihret and Ebner have been fully considered and with regard to the use of GILZ as a marker they are found persuasive. Therefore, the rejection has been withdrawn. However, upon further consideration, a new ground(s) of rejection is made in view of newly cited prior art reference Cohen et al (Blood 2006-from IDS filed 10/04/2023).
In response to applicant's argument that the prior art does not teach or suggest selecting immune-stimulatory autologous dendritic cells using a tri-marker approach with ICAM-1, PLAUR and GILZ as claimed is not straightforward, the fact that the inventor has recognized another advantage which would flow naturally from following the suggestion of the prior art cannot be the basis for patentability when the differences would otherwise be obvious. See Ex parte Obiaya, 227 USPQ 58, 60 (Bd. Pat. App. & Inter. 1985).
In the current case, one of ordinary skill in the art would have been motivated to observe the surface markers characteristic of mature dendritic cells in the method of Edelson ‘365 because Mihret, Ebner and Cohen indicate that this ensures that the desired mature dendritic cells are obtained as the product. One of ordinary skill in the art would have had a reasonable expectation of success because Edelson ‘365, Mihret and Ebner are drawn to obtaining dendritic cells from in vitro differentiated hematopoietic precursor cells.
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to LAURA J SCHUBERG whose telephone number is (571)272-3347. The examiner can normally be reached 8:30-5:00 EST.
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LAURA J. SCHUBERG
Primary Examiner
Art Unit 1631
/LAURA SCHUBERG/Primary Examiner, Art Unit 1631