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 .
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 Action is in response to the papers filed on 11/10/2025. Claims 1-16, 82, and 186 are currently pending. Claims 1-2, 6-7, and 11-14 have been amended by Applicant’s amendment filed on 11/10/2025.
Election/Restrictions
Applicant's election without traverse of Group I, which include claims 1-15, and election of species for Group I, a diabetes related disease and a symptom of a diabetes related disease, an agent that reduces expression of CDC50A, and an inhibitory nucleic acid for the specific target and specific agent, in the reply filed on 02/26/2025 was previously acknowledged.
Claims 16, 82, 186 were previously withdrawn from consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected subject matter, there being no allowable generic or linking claim. Claims 3-5, 8-10 were previously withdrawn from further consideration pursuant to 37 CPR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. The requirement for restriction is still deemed proper and is therefore made final.
Therefore, claim 1-2, 6-7, and 11-15 are currently under examination to which the following grounds of rejection are applicable.
Priority
The instant application is a 371 of PCT/IB2020/000680 filed on 12/31/2019, which claims priority to PRO 62/891,188 filed on 08/23/2019.
Thus, the earliest possible priority for the instant application is 08/23/2019.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 04/05/2022, 08/04/2022, and
02/26/2025 were filed before the mailing date of the non-final office action. The submission is
in compliance with the provisions of 37 CPR 1.97. Accordingly, the information disclosure
statement is being considered by the examiner.New objections in response to Applicant’s arguments or amendments:
Claim Objections
The amendment to the claims filed on 11/10/2025 does not comply with the requirements of 37 CFR 1.121(c) because the proper status of withdrawn claims 3-5, 8-10, 16, 82 and 186
is not properly identified with respect to the previously presented claims, filed on 2/26/2025. Amendments to the claims filed on or after 2/26/2025 must comply with 37 CFR 1.121(c) which states:
(c) Claims. Amendments to a claim must be made by rewriting the entire claim with all changes (e.g., additions and deletions) as indicated in this subsection, except when the claim is being canceled. Each amendment document that includes a change to an existing claim, cancellation of an existing claim or addition of a new claim, must include a complete listing of all claims ever presented, including the text of all pending and withdrawn claims, in the application. The claim listing, including the text of the claims, in the amendment document will serve to replace all prior versions of the claims, in the application. In the claim listing, the status of every claim must be indicated after its claim number by using one of the following identifiers in a parenthetical expression: (Original), (Currently amended), (Canceled), (Withdrawn), (Previously presented), (New), and (Not entered).
Any further claim amendments must comply with 37 CFR 1.121(c) or they may not be entered.
Withdrawn Objections/Rejections in response to Applicants’ arguments or amendments
Objections – Claims
In view of Applicants’ amendment to claims 1, 2 and 7, the objection has been withdrawn.
Maintained and modified rejections in response to Applicants’ arguments or amendments
Claim Rejections - 35 USC § 112(b)
Claim 6 remains 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.
Claim 6 is indefinite in its recitation of "at least 30% positive for SDC2" because it is unclear in relation to what the evaluation of the positive for SDC2 is done. A population of mammalian stromal stem cells comprising additional markers? A population of mammalian stromal stem cells that has not been treated with the agent? As such the metes and bounds of the claim are indefinite.
In view of Applicants’ amendment to claims 1-2, 7, and 11-15, the rejection of claims 1-2, 7, and 11-15 under 35 U.S.C. 112(b) has been withdrawn.
Claim Rejections - 35 USC § 103
Claims 1-2, 6-7, 11-15 remain rejected under 35 U.S.C. 103 as being unpatentable over Elliman et al. (US 2022/0228122 Al, IDS; hereafter "Elliman"), Nagata et al. (US 20170023548 Al, IDS; hereafter "Nagata") and Yin et al. (Yin Y., Cancer Immunol Res. 1(4):256-268; 2013; hereafter "Yin")
Regarding Claims 1-2 and 7, Elliman teaches a method of treating an inflammatory disease by administration of stromal stem cells (SDC2+ cells) to a site of the inflammation response (Pg 2, Paragraph 0007). Elliman further demonstrates the method of their invention results in the reduction of inflammation in a rat model of ARDS (Acute Respiratory Distress Syndrome) when administering human mesenchymal stem cells (hMSC) as measured by increased oxygenation (Figures 7 and 8). Elliman also teaches their invention can be used to treat multiple diabetic complications, for example cardiomyopathy, kidney disorders, diabetic ulcers etc. (with respect to "diabetic related disease") (Pg. 21, Paragraph 0131).
Elliman does not teach the cells have been treated with an agent to reduce the expression of CDC50A as in claim 1, resulting in a reduction of CDC50 activity as in claim 2. Although Elliman teaches genetic modification strategies to engineer their cell population prior to
administration (Pg. 5, end of Paragraph 0009), they do not teach a genetic modification using an inhibitory nucleic acid specifically to target CDC50 as in claim 7.
Nagata teaches inhibition of CDC50A by multiple methods, including inhibitory nucleic acids (e.g. siRNA, miRNA, CRISPR, etc.) (Pg. 4, Paragraph 0059). Nagata teaches that reduced expression of CDC50A will enhance phosphatidyl serine (PS) exposure and could be used for prophylaxis or treating cancers or autoimmune diseases (Pg. 4, Paragraph 0069). Nagata also demonstrates that CDC50A deficient cell lines have reduced flippase capacity of, resulting in constitutive exposure of PS (Pg. 2, Paragraph 0031-0037; Figure 5A-F).
Moreover, Yin teaches that phosphatidyl serine (PS) can prevent immune and inflammatory reactions (Pg. 256, 2nd Column, final paragraph).
It would have been prima fascia obvious to one of ordinary skill in the art prior to the filing of the instant application to combine the methods of Elliman which teach the generation of a SDC2+ stromal stem cell for the treatment of inflammatory pathologies (such as diabetes related diseases discussed above) with the teachings of Nagata and Yin who demonstrate CDC50A inhibition/knockout results in constitutive PS exposure and that PS can prevent inflammatory response. Thus, treatment of a population of mammalian stromal stem cells with an agent that reduces expression of transmembrane protein 30A (CDCS0A) would have been obvious to one of ordinary skill in the art. One would be motivated to combine these teachings because they motivate one of ordinary skill in the art to produce a genetically modified stromal stem cell, engineered to treat inflammatory processes.
There would have been reasonable expectations of success in combining these teachings as one of ordinary skill in the art would recognize to combine known elements in the art to give predictable results.
Regarding Claim 6, Ellman, Nagata, and Yin together render obvious the method of claim 1, as iterated above, the content of which is incorporated herein, in its entirety.
Moreover, Ellman teaches the SDC2+ cell population of their invention to be at least 20% SDC2+ (Pg. 1, Paragraph 0005). Optimization of the percentage of SDC2+ cell population would have been a matter of routine optimization based on influential considerations in the design of the assay such as quality control, number of SDC2+ cell population/ ml of collected cells, viability of cells and others.
Regarding Claims 11-14, Ellman, Nagata, and Yin together render obvious the method of claim 1, as iterated above, the content of which is incorporated herein, in its entirety.
The recitation of "wherein the method ( of claim 1) increases to the total number of
mitochondria in the cell "(claim 11), "wherein the method increases the total volume of mitochondria in the cell" (claim 12), "wherein the method increase the phosphatidylserine levels (PS) levels on the cell surface" (claim 13), and wherein the method increases the itaconate levels in the cell" ( claim 14) are inherent to the result based on the method of claim 1 comprising the step of administering a population of stromal stem cells to the individual in an amount effective to reduce at least one symptom of the inflammatory disease.
Because Ellman, Nagata, and Yin together render obvious the method as claimed, the effect of the method is also rendered obvious by the combination of references, absent evidence to the contrary. Further, these wherein clauses of claims 11-14 are directed towards the results of the methods. These clauses do not add limitations to the claim, the merely add a description of potential outcome. These claims do not require any active step be carried out. The patentability of a method claim is determined by active steps required by the claim not by the results obtainable from the method.
Regarding Claim 15, Ellman, Nagata, and Yin together render obvious the method
of claim 1, as iterated above, the content of which is incorporated herein, in its entirety.
As discussed above Elliman teaches their invention can be used to treat multiple diabetic complications, for example cardiomyopathy, kidney disorders, diabetic ulcers etc. (with respect to "diabetic related disease") (Pg. 21, Paragraph 0131). Subjects with these diabetic related diseases would inherently be symptomatic.
Response to Applicants’ Arguments as they apply to the rejection of claim(s) 1-2, 6-7, 11-15 under 35 U.S.C. 103
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At pages 6 of the remarks filed on 11/10/2025, Applicants essentially argue that the rejection of claims be withdrawn as claims are not obvious over the prior art of Elliman, Nagata, and Yin. The entirety of the argument is attached below for reference.
These arguments have been fully considered but have not been found persuasive.
In response to applicant's argument pertaining to Elliman, Nagata, and Yin, it appears that Applicant is arguing that the cited references do not expressly suggest the claimed invention.
However, it is well established in case law that a reference must be considered not only for what it expressly teaches, but also for what it fairly suggests. In re Burkel, 201 USPQ 67 (CCPA 1979). Furthermore, in the determination of obviousness, the state of the art as well as the level of skill of those in the art are important factors to be considered. The teaching of the cited references must be viewed in light of these factors.
Arguments presented by applicant cannot take the place of evidence in the record. See In re De Blauwe, 736 F.2d 699, 705, 222 USPQ 191, 196 (Fed. Cir. 1984); In re Schulze, 346 F.2d 600, 602, 145 USPQ 716, 718 (CCPA 1965); In re Geisler, 116 F.3d 1465, 43 USPQ2d 1362 (Fed. Cir. 1997) (“An assertion of what seems to follow from common experience is just attorney argument and not the kind of factual evidence that is required to rebut a prima facie case of obviousness.”). See MPEP § 716.01(c) for examples of applicant statements which are not evidence and which must be supported by an appropriate affidavit or declaration.
As recited in the 103 rejection above, the teachings of the Elliman, Nagata, and Yin references are cited to show that it would have been prima fascia obvious to one of ordinary skill in the art prior to the filing of the instant application to combine the methods of Elliman which teach the generation of a SDC2+ stromal stem cell for the treatment of inflammatory pathologies (such as diabetes related diseases) with the teachings of Nagata and Yin who demonstrate CDC50A inhibition/knockout results in constitutive PS exposure and that PS can prevent inflammatory response. One would be motivated to combine these teachings because they motivate one of ordinary skill in the art to produce a genetically modified stromal stem cell, engineered to treat inflammatory processes.
There would have been reasonable expectation of success in combining these teachings as one of ordinary skill in the art would recognize to combine known elements in the art to give predictable results. Therefore the applicants arguments are not considered persuasive and the claims remain rejected.
Conclusion
No claims are 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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KODYE LEE ABBOTT whose telephone number is (703)756-1111. The examiner can normally be reached M-F 8-5.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Maria G. Leavitt can be reached on (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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/KODYE LEE ABBOTT/Examiner, Art Unit 1634
/MARIA G LEAVITT/Supervisory Patent Examiner, Art Unit 1634