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 .
Response to Amendment
Claims 2 and 4-7 have been cancelled. Claims 1 and 3 have been amended as requested in the amendment filed on 30 July 2026. Following the amendment, claims 1, 3, and 8 are pending in the instant application, and are under examination in the instant office action.
Claim Rejections - 35 USC § 101 (New, Necessitated by Amendment)
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 1, 3, and 8 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception without significantly more. The claim(s) recite(s) “calculating cell migration as the induced events counted in the chemotactic compartment, in relation to basal migration events”, which is a mathematical concept, and one of the enumerated abstract ideas that are judicially excepted subject matter MPEP 2106.04(a). A mathematical relationship is a relationship between variables that may be expressed in words or using mathematical symbols. This judicial exception is not integrated into a practical application because the claims recite none of the considerations under MPEP 2106.05(a-c), (e) and (h) that provide for integration of the mathematical concept into a practical application. Further, the claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the steps recited in addition to the calculating step, were all well-understood routine and conventional activities in the art prior to filing.
The claim is directed to a method, which is one of the statutory categories of invention (STEP 1:YES).
This claim recite the new limitation “calculating cell migration as the induced events counted in the chemotactic compartment, in relation to basal migration events”. Therefore the claims recite at least one judicial exception (STEP 2A, Prong One: YES).
According to Step 2A, Prong Two, the claims are next evaluated with respect to whether the judicial exception is integrated into a practical application. This analysis turns to the additional elements recited within the claim, which in independent claim 1 are steps (a) through (e). None of these additional steps reflect an improvement within the technical field; there are no additional elements that apply the judicial exception to a particular machine or transformation. Thus, the additional steps do not provide for integration of the judicial exception ((STEP 2A, Prong Two: NO).
The specification recites that many of steps (a) through (e) were known in the art before filing. For example, the specification states: “In accordance with the method of the present invention, the HPC could be isolated by any known method which concentrates the HPC” (pg. 8); “In accordance with the present invention, the cellular compartment, the adhesion compartment and the chemotactic compartment correspond to locations/sections of whatever known device in the prior art which permits cellular migration” (pg. 10); and “in accordance with the method of the present invention, the cells which migrate from the cellular compartment towards the chemotactic compartment and which are recovered from the chemotactic compartment can be counted by any of the known methods in the prior art, such as fluid cytometry, hematocytometry, or counting in a Neubaur chamber” (pg. 11).
Therefore, in accordance with Berkheimer Memo III.A.1, the examiner has cited express statements in the specification indicating that the additional elements are sufficiently well-known and that the specification does not need to describe the particulars thereof. In other words, the disclosure describes no new technology, but merely refers to techniques and elements that were known in the art at the time of filing.
Lastly, in accordance with Berkheimer Memo III.A.III. the examiner cites publications within the field of technical expertise, that demonstrate the well-understood, routine, conventional nature of the additional element(s). The Hidalgo art made of record in the previous Office action teaches each of steps (a) through (e) as outlined in the art rejection below. Therefore the steps/elements in addition to the judicial exception do not set forth an inventive concept over what was well-understood, routine and conventional activities.
Accordingly, the method of claim 1, 3, and 8 are directed to the judicial exception without significantly more and are rejected.
Claim Rejections - 35 USC § 102
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 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.
As currently amended, Claims 1, 3, and 8 are rejected 35 U.S.C. 102(a)(1) as being anticipated by Hildago et al. Experimental Hematology, 29: 345-355, 2001 as evidenced by Mabotuwana et al, Stem Cell Reviews and Reports (2022) 18:2606–2628.
MPEP §2131.01 provides guidance as to 35 U.S.C. 102 rejections over multiple references. Such rejection has been held to be proper when the extra references are cited to: (C) Show that a characteristic not disclosed in the reference is inherent. The MPEP states: “To serve as an anticipation when the reference is silent about the asserted inherent characteristic, such gap in the reference may be filled with recourse to extrinsic evidence. Such evidence must make clear that the missing descriptive matter is necessarily present in the thing described in the reference, and that it would be so recognized by persons of ordinary skill.” Continental Can Co. USA v. Monsanto Co., 948 F.2d 1264, 1268, 20 USPQ2d 1746, 1749 (Fed. Cir. 1991) (The court went on to explain that “this modest flexibility in the rule that 'anticipation' requires that every element of the claims appear in a single reference accommodates situations in which the common knowledge of technologists is not recorded in the reference; that is, where technological facts are known to those in the field of the invention, albeit not known to judges.” 948 F.2d at 1268, 20 USPQ at 1749-50.). Note that the critical date of extrinsic evidence showing a universal fact need not antedate the filing date. See MPEP §2124. The Mabotuwana et al. reference, which does not antedate the filing date, is relied upon as evidence of the contents of mesenchymal stromal cell conditional medium comprise a mixture of factors comprising Eotaxin, HGF, IL-6, IL-8, MCP-1, VEGF-1 and G-CSF.
On pages 4-11 of Remarks filed 30 July 2026, Applicant traverses the rejection based on Hildago, on the following grounds.
Applicant argues Hidalgo does not teach the newly added limitations: that the compartment is haptotactic. Applicant further argues the mesenchymal stromal cell conditional medium comprises a mixture of factors, but this is remedied by the added Mabotuwana reference. Additionally, Claim 1 was amended to recite calculating cell migration as induced events relative to basal migration events. On pages 6-7 of Remarks Applicant provides evidence that these factors in addition to VCAM-1 adhesion molecule increase the migration of cells, and Applicant asserts Hidalgo fails to suggest the associated technical effects of the claimed amendments.
While these arguments have been reviewed in full, they are not persuasive. The new reference has been added to teach the mixture of factors in mesenchymal stromal cell conditional medium.
Regarding amended Claim 1, the Hildago et al. prior art teaches an in vitro Transwell migration assay. While there is no explicit definition of “haptotactic” within the instant specification, page 10 states “enables fixing the adherent substrate (Haptotactic) and enables passage of the cells there through.” The Transwell migration membrane that separates the two chambers fulfills this requirement. Hidalgo teaches incubating an adhesion solution comprising adhesion molecules, and vascular cell adhesion molecule-1 (VCAM-1), wherein it states, “For adhesion to VCAM-1, we used the soluble seven-extracellular domain recombinant human VCAM-1 (R&D Systems)” (pg. 346, Cell adhesion assays). Hidalgo teaches a migration buffer comprising mesenchymal stromal cell conditioned medium wherein it says bone marrow cells (which necessarily comprise mesenchymal stromal cells) were added to the upper chamber of the Transwells and incubated for 7 hours before cell adhesion assays (pg.346, Cell adhesion assays) and the prior art calls this “adhesion medium”. The prior art teaches adding a migration buffer to a chemotactic compartment which comprises a chemotactic agent (“adhesion medium” of the reference; pg. 347, Chemotactic assay). Hidalgo teaches suspending a cellular phase of a source of HPC in added migration buffer and incubation thereof in a cellular compartment, wherein it states: CD34hi BM cells resuspended in adhesion medium. The prior art teaches these cells are “hematopoietic progenitor cells” (see for example, Figure 1 legend). Lastly, the prior art teaches recovering the content of the chemotactic compartment and count the cells which migrated; wherein the cellular compartment is separated from the chemotactic compartment by an adhesion surface or adhesion compartment; and wherein the cellular compartment and the chemotactic compartment are in mutual communication via a continuous solution which comprises a chemotactic gradient. Viable migrated cells were counted in the flow cytometer by analyzing each sample in the same predetermined time and flow conditions.
While the Hidalgo prior art does not teach the “calculating” step of instant claim 1, but this is an abstract concept that is not patent eligible subject matter, and therefore cannot be the step that distinguishes over the prior art.
Lastly, Hidalgo says nothing about the components of mesenchymal stromal cell conditioned medium. However, the Mabotuwana et al. reference discloses that the cells disclosed in Hidalgo, bone marrow MSCs inherently release, Eotaxin, HGF, IL-6, IL-8, MCP-1, VEGF-1, and G-CSF (pg. 2617, Table 3, Human BM-MSCs, column titled Factors in conditioned media).
Therefore, the claim fails to distinguish over the method of Hidalgo.
Regarding amended Claim 3, Hildago et al. teach 1 µg/mL of sVCAM-1 is used (pg. 346, Cell adhesion assay). Thus, the prior art teaches the method wherein the concentration of the adhesion molecule (namely, VCAM-1) is of the order of pg/mL to mg/mL.
Regarding Claim 8, the methods of Hildago et al. prior art teach, in both the cell adhesion assays and the Chemotactic assays, wherein the HPC are incubated at 37oC for 3 hours (pg. 347, Chemotactic assays) and cells were maintained “in a humidified atmosphere at 37 8 C and 5% CO2” (pg. 347, lines 4-5). Therefore, the prior art teaches HPCs are incubated for 2 - 5 hours at 37°C with an atmosphere of between 3 and 5% of CO2.
Therefore, the method of the invention fails to distinguish over the methods disclosed in the prior art of record, and claims 1, 3 and 8 stand as rejected.
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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/S.N.M/Examiner, Art Unit 1675
/KIMBERLY BALLARD/Primary Examiner, Art Unit 1675
