DETAILED ACTION
The present application is being examined under the pre-AIA first to invent provisions.
Election/Restrictions
Applicant’s election of Group I, presently claims 1, 2, 4, 6-9, and 11-17, in the reply filed on 8/01/2025 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Claims 30, 33-35, and 60 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to nonelected inventions, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 8/01/2025.
Claims 1, 2, 4, 6-9, and 11-17 are under consideration on the merits.
Nucleotide and/or Amino Acid Sequence Disclosures
REQUIREMENTS FOR PATENT APPLICATIONS CONTAINING NUCLEOTIDE AND/OR AMINO ACID SEQUENCE DISCLOSURES
Items 1) and 2) provide general guidance related to requirements for sequence disclosures.
37 CFR 1.821(c) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.821(a) must contain a "Sequence Listing," as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.821 - 1.825. This "Sequence Listing" part of the disclosure may be submitted:
In accordance with 37 CFR 1.821(c)(1) via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter "Legal Framework") as an ASCII text file, together with an incorporation-by-reference of the material in the ASCII text file in a separate paragraph of the specification as required by 37 CFR 1.823(b)(1) identifying:
the name of the ASCII text file;
ii) the date of creation; and
iii) the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(1) on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation-by-reference of the material in the ASCII text file according to 37 CFR 1.52(e)(8) and 37 CFR 1.823(b)(1) in a separate paragraph of the specification identifying:
the name of the ASCII text file;
the date of creation; and
the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(2) via the USPTO patent electronic filing system as a PDF file (not recommended); or
In accordance with 37 CFR 1.821(c)(3) on physical sheets of paper (not recommended).
When a “Sequence Listing” has been submitted as a PDF file as in 1(c) above (37 CFR 1.821(c)(2)) or on physical sheets of paper as in 1(d) above (37 CFR 1.821(c)(3)), 37 CFR 1.821(e)(1) requires a computer readable form (CRF) of the “Sequence Listing” in accordance with the requirements of 37 CFR 1.824.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed via the USPTO patent electronic filing system as a PDF, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the PDF copy and the CRF copy (the ASCII text file copy) are identical.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed on paper or read-only optical disc, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the paper or read-only optical disc copy and the CRF are identical.
Specific deficiencies and the required response to this Office Action are as follows:
Specific deficiency - This application fails to comply with the requirements of 37 CFR 1.821 - 1.825 because the "Sequence Listing" part of the disclosure submitted as a PDF file (37 CFR 1.821(c)(2)) or on physical sheets of paper (37 CFR 1.821(c)(3)) is not the same as the CRF of the "Sequence Listing" as required by 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii). In this case, SEQ ID NO: 2-4 as disclosed on pages 18-19 of the replacement specification dated 9/03/2024 does not match SEQ ID NO: 2-4 of the CRF listing dated 9/03/2024.
Required response - Applicant must provide:
A replacement "Sequence Listing" as described above in items 1) c) or d) in accordance with 37 CFR 1.825(b)(1)(ii) or (iii); as well as
An amendment specifically directing its entry into the application as required by 37 CFR 1.825(b)(2)(ii);
A statement that identified the locations of any deletions, replacements or additions to the “Sequence Listing” as required by 37 CFR 1.825(b)(3);
A statement that the "Sequence Listing" added by amendment includes no new matter as required by 37 CFR 1.825(b)(5);
A statement that indicates support for the amendment in the application, as filed, as required by 37 CFR 1.825(b)(4); and
A statement that the content of the previously-filed CRF is identical to the "Sequence Listing" part of the disclosure added by amendment as required by 37 CFR 1.825(b)(7), where provided under item 1) c) or d) (note that where a "Sequence Listing" part of the disclosure is provided under item 1) a) or b), the text file will also serve as the CRF, and the statement of identity is not required);
OR
A CRF as required by 37 CFR 1.821(e)(1) or 1.821(e)(2); and
A statement that the content of the CRF is identical to the "Sequence Listing" part of the disclosure previously submitted as a PDF file (37 CFR 1.821(c)(2)) or on physical sheets of paper (37 CFR 1.821(c)(3)), as required by 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii).
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 11-17 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.
“can be” as recited in claims 11-17 blurs the metes and bounds of these claims because it is not clear if the limitations which follow this phrase are optional limitations or not as these claims do not recite any further manipulative steps. If Applicant intended these claims to recite optional limitations, then Applicant might overcome this rejection by adding the word “optional” prior to “can be” (i.e. the claims would read “endothelial cells optionally can be maintained…”). If Application intended these claims to further manipulatively limit claim 1 from which they depend, then Applicant might overcome this rejection by replacing “can be” with “are” (i.e. the claims would read “endothelial cells are maintained…”). Clarification and/or correction is required.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1, 2, 4, 6-9, and 11-17 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 2, 4, 6, and 7 of U.S. Patent No. 8,465,732 (cite number 3 as provided in the IDS dated 1/16/2024) in view of Maciag et al. (The Journal of Cell Biology (1981), 91, 420-426; Reference U).
In view of the indefiniteness rejections above and in the interest of compact prosecution, this rejection addresses the embodiment of claims 11-17 as optional limitations wherein said optional limitations are not required.
Claim 1 of the ‘732 patent claims a method comprising (a) introducing a nucleic acid sequence encoding adenovirus E4ORF1 under the control of a promoter into isolated endothelial cells, wherein the nucleic acid sequence does not encode adenovirus E4ORF2, E4ORF3, E4ORF4, E4ORF5, or E4ORF6, such that the endothelial cells express E4ORF1 to a level sufficient to maintain or expand the isolated endothelial cells in culture, and (b) culturing the isolated endothelial cells expressing E4ORF1, reading in-part on instant claims 1 and 11-17. In the same order, claims 2, 4, 6, and 7 of the ’732 patent read in-part on instant claims 2, 4, 6, and 7. None of claims 1, 2, 4, 6, and 7 of the ‘732 patent recites pro-angiogenic factors and do not recite VEGF, reading on the negative limitations of claims 8 and 9.
Regarding instant claim 1, the ‘732 patent does not claim a method further performing one or more serial passages of the endothelial cells.
Maciag teaches a method of serially passaging/propagating human endothelial cells in vitro, which is advantageous to delay premature senescence of the endothelial cells (Abstract), reading in-part on instant claim 1.
It would have been obvious to a person of ordinary skill in the art before the invention was made to add the serially passaging methods of Maciag to the methods of the ‘732 patent. A person of ordinary skill in the art would have had a reasonable expectation of success to do so because both Maciag and the ‘732 patent are directed towards methods of culturing endothelial cells. The skilled artisan would have been motivated to do so because the addition would be predictably advantageous to delay premature senescence of the endothelial cells in the methods of the ‘732 patent.
Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill at the time the invention was made.
Claims 1, 2, 4, 6-9, and 11-17 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 15, 16, 18, 20, and 21 of U.S. Patent No. 9,944,897 (cite number 2 as provided in the IDS dated 1/16/2024) in view of Maciag et al. (The Journal of Cell Biology (1981), 91, 420-426; Reference U).
In view of the indefiniteness rejections above and in the interest of compact prosecution, this rejection addresses the embodiment of claims 11-17 as optional limitations wherein said optional limitations are not required.
Claim 15 of the ‘897 patent claims a method for maintaining or expanding endothelial cells in culture, comprising: (a) introducing a nucleic acid sequence encoding adenovirus E4ORF1 under the control of a promoter into isolated endothelial cells such that the endothelial cells express E4ORF1 to a level sufficient to maintain or expand the isolated endothelial cells in culture, wherein the endothelial cells do not contain or express nucleic acid sequences that comprise the entire adenovirus E4 region; and (b) culturing the isolated endothelial cells expressing E4ORF1, reading in-part on claims 1 and 11-17. In the same order, claims 16, 18, 20, and 21 of the ‘897 patent read in-part on instant claims 2, 4, 6, and 7. None of claims 15, 16, 18, 20, and 21 of the ‘897 patent recites pro-angiogenic factors and do not recite VEGF, reading on the negative limitations of claims 8 and 9.
Regarding instant claim 1, the ‘897 patent does not claim a method further performing one or more serial passages of the endothelial cells.
Maciag teaches a method of serially passaging/propagating human endothelial cells in vitro, which as advantageous to delay premature senescence of the endothelial cells (Abstract), reading in-part on instant claim 1.
It would have been obvious to a person of ordinary skill in the art before the invention was made to add the serially passaging methods of Maciag to the methods of the ‘897 patent. A person of ordinary skill in the art would have had a reasonable expectation of success to do so because both Maciag and the ‘897 patent are directed towards methods of culturing endothelial cells. The skilled artisan would have been motivated to do so because the addition would be predictably advantageous to delay premature senescence of the endothelial cells in the methods of the ‘897 patent.
Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill at the time the invention was made.
Claims 1, 8, 9, and 11-17 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 22 of U.S. Patent No. 10,865,379 (cite number 1 as provided in the IDS dated 1/16/2024) in view of Maciag et al. (The Journal of Cell Biology (1981), 91, 420-426; Reference U).
In view of the indefiniteness rejections above and in the interest of compact prosecution, this rejection addresses the embodiment of claims 11-17 as optional limitations wherein said optional limitations are not required.
Claim 22 of the ‘379 patent claims a method culturing a population of E4ORF1-expressing endothelial cells, wherein the endothelial cells do not contain or express nucleic acid sequences that comprise the entire adenovirus E4 region, reading in-part on claims 1 and 11-17. Claim 22 of the ‘379 patent does not recite pro-angiogenic factors and does not recite VEGF, reading on the negative limitations of claims 8 and 9.
Regarding instant claim 1, the ‘379 patent does not claim a method further performing one or more serial passages of the endothelial cells.
Maciag teaches a method of serially passaging/propagating human endothelial cells in vitro, which as advantageous to delay premature senescence of the endothelial cells (Abstract), reading in-part on instant claim 1.
It would have been obvious to a person of ordinary skill in the art before the invention was made to add the serially passaging methods of Maciag to the methods of the ‘379 patent. A person of ordinary skill in the art would have had a reasonable expectation of success to do so because both Maciag and the ‘379 patent are directed towards methods of culturing endothelial cells. The skilled artisan would have been motivated to do so because the addition would be predictably advantageous to delay premature senescence of the endothelial cells in the methods of the ‘379 patent.
Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill at the time the invention was made.
Allowable Subject Matter
The following is a statement of reasons for the indication of allowable subject matter: The method of independent claim 1 are free of the prior art. The nearest prior art reference is considered Rafii et al. (Circ. Res. (2001), 88, 903-910; cite number 46 as provided in the IDS dated 1/16/2024), which is directed towards compositions comprising endothelial cells infected with the adenovirus E4 gene under the control of the CMV promoter (p904, subheadings “Preparation of ECs” and “Construction of Advectors”). However, there is no motivation to modify Rafii’s complete E4 coding sequence to the claimed E4ORF1 coding sequence in combination with any of the other six ORFs in the adenovirus E4 gene to arrive at the claimed composition comprising the E4ORF1 coding sequence in combination with the other 6 ORFs of the E4 gene that does not comprise the entire adenovirus E4 region. While O’Shea et al. (The EMBO Journal (2005), 21, 1211-1211; cite number 39 as provided in the IDS dated 1/16/2024), contemplates the combination of E4ORF1 and E4ORF4, O’Shea is directed towards small airway epithelial cells (SAECs), and so there would be no motivation for a person of ordinary skill in the art to look beyond the endothelial cells taught by Rafii.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SEAN C BARRON whose telephone number is (571)270-5111. The examiner can normally be reached 7:00am-3:30pm EDT/EST (M-F).
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/Sean C. Barron/Primary Examiner, Art Unit 1653