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 .
Election/Restrictions
This action is in response to the papers filed on 05/19/2026. Claims 70-89 are currently pending as per claims filed on 05/13/2024. Claims 1-69 were previously canceled as per claims filed on 05/13/2024.
Applicant’s election without traverse of Group I, which include 70-82 drawn to a composition comprising E40RF1 + endothelial cells in a freezing medium containing cryopreservative, in the reply filed on 05/19/2026 is acknowledged.
Claims 83-89 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected subject matter, there being no allowable generic or linking claim. Note that Group III comprises claim 89 and not claims 83-88 as mistakenly stated in the restriction requirement of 12/119/2025. The examiner appreciates the correction.
The requirement for restriction between Groups I-III is still deemed proper and is therefore made FINAL. Because Applicant did not distinctly and specifically point out the supposed errors in the examiner’s action, and further, did not specifically traverse the election requirement, the election was treated as an election without traverse (MPEP § 818.03(a)).
Therefore, claims 70-82 are subject to examination to which the following grounds of rejection are applicable.
Priority
The instant application is a 371 of PCT/US21/45388 filed on 08/10/2021, which claims priority to PRO 63/063,668 filed on 08/10/2020.
Thus, the earliest possible priority for the instant application is 08/10/2020.
Information Disclosure Statement
No IDS has been filed.
Drawings
The drawings are objected to because as the specification refers to Figure 5 a and b. Figure 5 of the drawing contains no labeling referencing a and b. Appropriate correction is required. Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 78, and 81-82 are 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 78 recites “A composition according to claim 71, comprising… (b) endothelial growth media…”. It is unclear exactly what “endothelial growth medium” is intended to mean or what the composition of an “endothelial growth medium” can include. The instant specification has no mention of “endothelial growth medium”, as such the metes and bounds cannot be determined. Therefore, the claim is rendered indefinite. For the sake of compact prosecution, the claims with be examined as only requiring an appropriate cell culture medium for claim 78.
Claims 81-82 inherit these deficiencies and are rejected insofar as they depend from claim 1.
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) 70-71 and 74-82 are rejected under 35 U.S.C. 103 as being unpatentable over Rafii et al. (US 10,865,379 B2, filed 2018; hereafter “Rafii”) in view of Zeitlin et al. (US 2019/0261623 Al, filed 2018; hereafter “Zeitlin”).
Regarding Claim 70-71, Rafii teaches culture and expansion of engineered HUVECs comprising a nucleic acid encoding E4ORF1 protein (Column 1, line 64- Column 2, line 11), which can be used for treatment of tumors (Column 2, lines 54-65). Moreover, Rafii teaches the use of cryopreservation methods to preserve these cells.
Rafii does not teach that 50 million cells per ml to about 150 million cells are per ml are preserved in cryopreservation media.
Zeitlin cures the deficiencies of Rafii as Zeitlin teaches a composition comprising cells that are cryopreserved in which the cell number can be up to 50 million cells per mL (Pg. 1, Paragraph 0005). Zeitlin further teaches that cell viability does not change as a function of cell density frozen (Pg. 42, Paragraph 0381). It would have been obvious to a person of ordinary skill in the art at the time of the instant application to include within the cell culture method of Rafii an optimized cryopreservation protocol such as taught by Zeitlin to allow for preservation of higher number of cells together. One of ordinary skill in the art would be motivated to combine these methods as they would recognize the benefit of having a higher density cell population preserved together as this would reasonably increase the number of viable therapeutic cells available for use after storage and thawing.
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 Claims 74-77, Rafii and Zeitlin together render obvious the composition of claim 70. Moreover, Zeitlin teaches the composition of their invention can include human serum albumin (HSA) from 1 to 17% (Pg. 2, Paragraph 0008), for instant claims 74-75, and dimethylsulfoxide (DMSO) at 1 to 15% (Pg. 2, Paragraph 0011), for instant claims 76-77.
Regarding Claim 78, Rafii and Zeitlin together render obvious the composition of claims 70 and 71. As discussed in the rejection to claims 74-77 above, Zeitlin also teaches the use of DMSO and HSA within their invention which render obvious the concentrations provides in the instant claim (Pg. 2, Paragraph 0008 and 0011). Moreover, Zeitlin teaches multiple culture media formulations (Pg. 28, from Paragraph 0256). This includes the use of supplemented endothelial growth factor (Pg. 28, Paragraph 0260).
Regarding Claim 79-82, Rafii and Zeitlin together render obvious the composition of claim 70. Moreover, Zeitlin teaches the use of bags suitable for cryopreservation (Pg. 31, paragraph 0289 - 0291) and the bags can be suitable for medical use, such as intravenous administration (aseptic, closed system).
Claim(s) 73-74 are rejected under 35 U.S.C. 103 as being unpatentable over Rafii et al. (US 10,865,379 B2, filed 2018; hereafter “Rafii”) in view of Zeitlin et al. (US 2019/0261623 Al, filed 2018; hereafter “Zeitlin”) as applied to claim 70 above and further in view of US 2016/0100570 A1, filed 2015).
Regarding Claims 72-73, Rafii and Zeitlin together render obvious the composition of claim 70. However, they do not teach cryopreservation of cells at a density of from about 75 million cells per ml to about 125 million cells per ml (as recited in instant claim 72) or a density of about 100 million cells per ml (as recited in claim 73).
Jin et al. cures these deficiencies as they teach production of ultra-high density cell cultures that can be cryopreserved at unexpectedly high cell densities without the need for any cell concentration steps, while retaining excellent cell viability for later use in production cell culture. (Paragraph 0003, Summary). Jin et al. teaches the high density populations at 100 million cells per mL (reading on ranges of the instant claims 72-73). It would have been obvious to a person having ordinary skill in the art to have modified the culture and cryopreservation methods as taught by Rafii and Zeitlin to further include the teachings of Jin to produce an ultra-high density cell culture for cryopreservation. As Jin teaches the benefits of a cell composition at 100 million cells per mL, and a person of ordinary skill in the art would have readily understood that the cell density is a result effective variable when cryopreserving cells from the teachings of Zeitlin and Jin, there would have been motivation to determine an appropriate number of cells to preserve cells within a method for culture and preservation of HUVECs to allow for the most success in obtaining viable post-thaw cells to achieve a desired population of cells.
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.
Conclusion
Claims 70-82 are rejected. No claims are allowed.
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.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Maria G. Leavitt can be reached at (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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