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 11/19/2025. Claims 1-10 and 127-131 are currently pending. Claims 1, 2, 4, 5, 9 and 130 have been amended and claims 106-115 and 126 have been canceled by Applicant’s amendment filed on 11/19/2025.
Election/Restrictions
Applicant’s election without traverse of Group II, which include claims 2, 4 and 126-131, in the reply filed on 04/28/2025 was previously acknowledged.
Claims 1, 3, 5-10, 106-115 (106-115 and 126 now cancelled) were previously withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected subject matter, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 02/03/2025. The requirement for restriction was previously made final in the office action filed 07/28/2025.
Therefore, claims 2, 4, and 127-131 are currently under examination to which the following grounds of rejection are applicable.
Priority
The instant application is a 371 of PCT/US20/67507 filed on 12/30/2020, which claims priority to PRO 62/992,745 filed on 03/20/2020 and PRO 62/955,820 filed on 12/31/2019.
Thus, the earliest possible priority for the instant application is 12/31/2019.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 11/19/2025 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.
Withdrawn Objections/Rejections in response to Applicants’ arguments or amendments
Objections – Claims
The objection to claims 2 and 4 has been withdrawn in view of Applicants’ amendments.
Claim Rejection - 35 USC § 112(b)
In view of Applicants’ amendment, the rejection of claims 2, 4, and 126-131 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, has been withdrawn.
Applicant’s arguments with regard to a withdrawn objection/rejection are moot.
Maintained and modified rejections in response to Applicants’ arguments or amendments
Claim Rejections - 35 USC § 103
Claims 2, 4, 127-128, and 131 remain rejected under 35 U.S.C. 103 as being unpatentable over Minoru et al. (US 2019/0282659 Al, IDS; hereafter “Minoru”) and Namdaroglu et al. (Namdaroglu S, Transfus Apher Sci., 2017; hereafter “Namdaroglu”, of record).
Regarding Claim 2 and 127-128, Minoru teaches a method of treating a disease (including diseases of the blood) by transiently increasing expression of Zscan4 (Abstract). Minoru teaches “bone marrow, which includes hematopoietic stem cells and mesenchymal stem cells, will be aspirated from patients and then immediately exposed to Zscan4 (e.g., Sendai vector carrying human ZSCAN4). Alternatively, temperature-sensitive Sendai vectors can be used, as the expression of Zscan4 can be turned off by switching the temperature” (Pg. 46, Paragraph [0427]).
Minoru teaches the human bone marrow or blood cells can be CD34+ cells (Pg. 93, Claim 123). Minoru teaches the temperature-sensitive Sendai viral vector comprises a heterologous nucleic acid comprising a coding region of human ZSCAN4 (Pg. 92, Claim 113). Moreover, the temperature-sensitive Sendai vector is functional at 35 °C, but can be inactivated when cultured at 37°C. (Pg. 234, Paragraph [0196], 5th line from bottom of page). Minoru teaches cells contacted with the Sendai vector were cultured at 35 degree C. for three days (FIG. 3A).
Minoru teaches the cells contacted with the Sendai vector are engrafted to treat a subject (Pg. 6, Paragraphs [0043, 0044]; Pg. 93, Claim 120, step ii).
Minoru does not teach “iv) incubating the contacted CD34+ cells at a permissive temperature of 33°C ± O.S°C for a period of about 12 to 24 hours”. However, it would have been obvious to one of ordinary skill in the art when performing the incubation to determine an optimal working temperature and incubation time through routine optimization.
"[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) (Claimed process which was performed at a temperature between 40°C and 80°C and an acid concentration between 25% and 70% was held to be prima facie obvious over a reference process which differed from the claims only in that the reference process was performed at a temperature of 100°C and an acid concentration of 10%.); see also Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382 ("The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages.") See MPEP 2144.05 II.
Minoru does not specifically teach an initial step i) of mobilizing hematopoietic stem cells from bone marrow cell to peripheral blood of a human subject suffering from the disease. Minoru does not teach the use of granulocyte-colony stimulation factor and plerixafor for mobilization (claim 127) or apheresis (claim 128) for the method of cell collection (with respect to instant claims 127 and 128). However, Minoru does teach that the procedure of their invention is similar to bone marrow transplantation procedures (Pg. 46, Paragraph [0427]).
Namdaroglu demonstrates mobilization was well known in the art to precede cell collection in bone marrow transplantation procedures (Pg. 836, Introduction, Paragraphs 1-3). Moreover, Namdaroglu teaches the use of granulocyte-colony stimulation factor (G-CSF) and plerixafor for mobilization (Pg. 839, Section 5.2) and the collection of cells from the peripheral blood using apheresis (Pg. 836, Introduction, Paragraph 1) (for instant claims 127 and 128).
It would have been obvious to one of ordinary skill in the art at the time of the instant application to have modified the method taught by Minoru to specifically include an initial step of mobilization using G-CSF and Plerixafor and a collection step utilizing apheresis as demonstrated by Namdaroglu because this would increase the yield of the desired hematologic stem cells cell type from bone marrow cell to peripheral blood of the subject from where CD34 + would be further isolated and modified and used for the subject treatment. It would have been a matter of combining known prior art elements according to known methods to yield predictable results since Namdaroglu’s mobilization and apheresis strategy was well known in the field and it would enhance the similar method of collection described by Minoru.
Regarding Claim 4, the combined teachings of Minoru and Namdaroglu render obvious claim 2. Additionally, Minoru teaches the temperature-sensitive Sendai vector is functional at 35 degree C., but can be inactivated when cultured at 37 degree C. (Pg. 234, Paragraph [0196]). Minoru also teaches that cells Zscan4+ may grow well in tissue culture at reduced temperatures, yet discontinue division once implanted into a patient and maintained at 37° C. (Pg. 39, paragraphs [0333] [0370]). Minoru teaches incubating the contacted CD34+ cells at a non-permissive temperature of 37°C ± 0.5°C for 3 days (Fig. 3). It would have been obvious for one of ordinary skill in the art that when the temperature-sensitive Sendai vector is incubated at a non-permissive temperature of 37°C , expression of human ZSCAN4 from Sendai vector the ceases, therefore it would have been obvious for one of ordinary skill in the art to reduce the contacted cells Zscan4+ to prevent inactivation of the Sendai vector depending on influential considerations in the design of the assay such number of contacted CD34+cells, variations in temperature, incubation time, expression of human ZSCAN4, transfection efficiency of vector carrying human ZSCAN4and other considerations. Further, it would have been obvious to one of ordinary skill in the art when performing the incubation to determine an optimal working temperature and incubation time through routine optimization.
"[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) (Claimed process which was performed at a temperature between 40°C and 80°C and an acid concentration between 25% and 70% was held to be prima facie obvious over a reference process which differed from the claims only in that the reference process was performed at a temperature of 100°C and an acid concentration of 10%.); see also Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382 ("The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages.") See MPEP 2144.05 II.
Regarding Claim 131, the combined teachings of Minoru and Namdaroglu render obvious claims 2 and 4. Additionally, Minoru teaches the cells of their invention can be administered intravenously from 20,000 to 2,000,000 (Pg. 38, Paragraph [0325]).
Claims 129 and 130 are rejected under 35 U.S.C. 103 as being unpatentable over Minoru et al. (US 2019/0282659 Al, IDS; hereafter "Minoru") and Namdaroglu et al. (Namdaroglu S, Transfus Apher Sci., 2017; hereafter "Namdaroglu") as applied to claim 2 above, in view of Brudecki et al (Brudecki, Laura et al., Infection and immunity, 2012; hereafter "Brudecki")
With regard to instant claim 2, the combined teaching of Minoru and Namdaroglu render obvious the claimed methodology, as iterated above in the 103 rejection the content of which is incorporated herein, in its entirety.
Regarding Claims 129-130, Minoru and Namdaroglu together do not teach CD34+ cells are isolated from the peripheral blood mononuclear cells by positive selection using an antiCD34 antibody and magnetic beads (with respect to instant claim 129) or that the CD34+ cells are washed and resuspended in a sterile, isotonic aqueous solution prior to infusion. Brudecki cures these deficiencies as they teach positive selection using anti-CD34 antibody and magnetic beads to isolate CD34+ cells from a bone marrow cell population and the CD34+ cells are washed resuspended in sterile solution (saline) before injection into a subject (Pg. 603, Section: Isolation and adoptive transfer of CD34+ HSCs).
It would have been obvious to one of ordinary skill in the art at the time of the instant application to have modified the combined methods of Minoru and Namdaroglu discussed above to include Brudecki's method of isolating CD34+ cell and preparing them for genetic modifications with temperature-sensitive Sendai viral vector follow by infusion because increasing the purity of the CD34+ cell would predictably yield a better therapeutic efficacy and preparation of the cells by washing and resuspending in saline would reduce the opportunity for adverse immune during adoptive transfer.
There would have been reasonable expectation of success in combining these teachings as combining prior art elements according to known methods to yield predictable results is obvious.
Response to Applicants’ Arguments as they apply to the rejection of claim(s) 2, 4, 127-128, and 131 under 35 U.S.C. 103
At pages 6 of the remarks filed on 11/19/2025, Applicants essentially argue that the rejection of claims be withdrawn as the amended claims are not obvious over the prior art of Minoru (referred to as “Ko” by the applicant) and Namdaroglu.
These arguments have been fully considered but have not been found persuasive.
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Applicant points to the following teachings of Minoru, provided below, from the remarks filed on 11/19/2025.
At pg. 7, Applicant provides exemplary passages from the instant specification, “Examples 11-14 and shown in Figs 19-24 of the pending application Applicant determined that incubating cells contacted with SeVts-ZSCAN4 at a lower permissive temperature for a shorter period of time resulted in sufficient ZSCAN4 expression for increasing length of telomeres in vitro and ex vivo.”, and points specifically to Fig 19 (image attached below) and provide from paragraph [207] the following: “The 3 and 6 hour incubations were too short to express ZSCAN4 protein at a detectable level. However, incubations of 16 and 24 hours at 33°C resulted in ZSCAN4 protein expression of 82% and 95% of CD34+ cells, respectively (FIG. 19). There was no further increase of the transfection efficiency and protein expression after 48 and 72 hour incubations at 33 °C.”
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The cited evidence appears to show that 3 and 6 were too short, 16 and 24 hours at 33 Celsius was sufficient. However, this does not establish the entire claimed range of 12 to 24 hours as critical, nor does it show that the claimed range produces a result different in kind, rather than degree, from Minoru’s teachings. Applicant has shown that certain shorter conditions with a broader optimization space were less effective and that 16-24 hours is a workable range.
Further, this data is limited to a specific construct, namely SeVts-ZSCA4, in a specific experimental context and this figure does not provide sufficient evidence of unexpected results across the broader scope of claimed subject matter.
The claimed 33°C ± 0.5°C for a period of about 12 to 24 hours appears to be an optimization of a result-effective variable. Minoru teaches the operative system and framework of contacting cells with a temperature sensitive Sendai vector encoding human Zscan4. Minoru teaches expression from the temperature sensitive sendai vector depends on culture conditions, including temperature and time (please see above rejections). As the art teaches that ZSCAN4 expression is dependent upon permissive temperature incubation and then temperature shift, it would have been routine to a skilled artesian to optimize the incubation temperature to obtain sufficient transient expression.
Applicant is arguing that the cited references do not expressly suggest the claimed invention. However, it appears the distinction between the instant application and the prior art is merely optimization of incubation temperature and duration, not in a fundamentally different method. 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.
Finally, the applicant argues the result are unexpected in view of Minoru.
Examples of statements which are not evidence and which must be supported by an appropriate affidavit or declaration include statements regarding unexpected results, commercial success, solution of a long-felt need, inoperability of the prior art, invention before the date of the reference, and allegations that the author(s) of the prior art derived the disclosed subject matter from the inventor or at least one joint inventor. MPEP 716.01(c). The teachings of Minoru and Namdaroglu render obvious claims 2, 4, 127-128, and 131 as recited in the 103 rejection above. Therefore the applicants arguments are not considered persuasive and the claims remain rejected.
Response to Applicants’ Arguments as they apply to the rejection of claim(s) 129-130 under 35 U.S.C. 103
At pg. 8, applicant essentially argues that claims 129-130 are not rendered obvious by Minoru and Namdaroglu as applied to Claim 2, in view of Brudecki et al. as Minoru and Namdaroglu together do not render obvious claim 2.
These arguments have been considered and are not persuasive. As discussed above in the response to applicants arguments as they apply to the rejection of claims 2, 4, 127-128, and 131, Minoru and Namdaroglu together render obvious claims 2, 4, 127-128, and 131.
Therefore, the applicants arguments are not considered persuasive and the claims remain rejected.
Conclusion
Claims 2, 4, and 127-131 are rejected.
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
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