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 .
Amendments
In the reply filed 4/10/2026, Applicant has amended Claims 22-28, and 33
Claims 22-33 are under consideration.
New Claim Objections
Claims 32 and 33 are objected to because of the following informalities: amendments to instant claim have not been properly submitted. Instant claim is objected to because of the following informalities: 37 C.F.R. 1.121. Manner of making amendments in application; Section (1)(ii) The full text of any replacement paragraph with markings to show all the changes relative to the previous version of the paragraph. The text of any added subject matter must be shown by underlining the added text. The text of any deleted matter must be shown by strike-through except that double brackets placed before and after the deleted characters may be used to show deletion of five or fewer consecutive characters. The text of any deleted subject matter must be shown by being placed within double brackets if strikethrough cannot be easily perceived. The specific deficiency in instant claims 32 and 33 is that the previously presented claims of 3/28/2023 was “according to claim 26” and “according to claim 27”, respectively, while the amended claims state “according to claim 31” and “according to claim 32”, respectively, yet the amended dependencies were not marked.
New Claim Rejections - 35 USC § 112(b)
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 32 and 33 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 pre-AIA the applicant regards as the invention.
Claim 32 recites the limitation "according to claim 31", and Claim 33 recites the limitation "according to claim 32". There is insufficient antecedent basis for this limitation in the claims because Claim 31 (and independent claim 25) are directed to methods of vectored immunoprophylaxis, and Claim 32 (and independent claim 26) are directed to methods of treating and/or preventing, thereby rendering Claims 32 and 33 indefinite as the scope of the claimed methods. Note that in light of the preambles of Claims 32 and 33, and for the sake of compact prosecution, they are being interpreted as being dependent on the methods of Claims 26 and 27, respectively. Appropriate correction is required.
Withdrawn 35 USC § 103
The prior rejection of Claims 22 and 28 under 35 U.S.C. 103 as being unpatentable over Endl et al., (WO2007/131774, filed 5/15/2007), in view of Akamatsu et al., (US 7,732,195, filed 11/01/2007) and Luo et al. (Blood, 2009,113:1422-1431) is withdrawn in light of Applicant’s amendment of Claim 22 to no longer require a variable light chain regions in the nucleic acid.
The prior rejection of Claims 27 and 33 under 35 U.S.C. 103 as being unpatentable over Endl et al., (WO2007/131774, filed 5/15/2007), in view of Akamatsu et al., (US 7,732,195, filed 11/01/2007) is withdrawn in light of Applicant’s amendment of Claim 27 to no longer require a variable light chain regions in the nucleic acid.
The prior rejection of Claims 23-26 and 29-32 are rejected under 35 U.S.C. 103 as being unpatentable over Endl et al., (WO2007/131774, filed 5/15/2007), in view of Akamatsu et al., (US 7,732,195, filed 11/01/2007) and Aebischer-Gumy et al. (US2017/0350886, filed 3/02/2015, published 12/07/2017) is withdrawn in light of Applicant’s amendment of Claim 23-26 to no longer require a variable light chain regions in the nucleic acid.
New Claim Rejections - 35 USC § 103
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 of this title, 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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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.
Claims 22 and 28 are rejected under 35 U.S.C. 103 as being unpatentable over Endl et al., (WO2007/131774, filed 5/15/2007), in view of Luo et al. (Blood, 2009,113:1422-1431)
With respect to claim 22, Endl teaches a method for inducing the physiologically-regulated expression of a membrane-anchored and/or secreted antibody of interest by a B cell line ex vivo (e.g., Sp2/0-Ag14 cells), comprising by exposing the B cell to the “pmIgG-A” vector comprising:
A) a sequence encoding a heavy chain variable domain (VH) specifically interacting with an antigen of interest;
B2) a sequence encoding heavy constant regions CH1-CH3,
B3) a first intronic sequence comprising a secretory specific polyA sequence (polyAs) comprising an internal 5’ splice site enabling the splicing of the first intronic sequence and polyAs,
[AltContent: textbox ([img-media_image1.png])]B4) a second intronic sequence comprising a an internal 3’ splice site and the M1 and M2 domains of the heavy chain transmembrane and cytoplasmic domains, and
B5) a membrane specific polyA sequence (polyAm) after the M2 domain (p. 59, last para., p. 61, p. 63, lines 19-23, Figs. 1-3, but see modified Fig. 1A adjacent),
wherein the nucleic acid encodes the variable heavy chain regions of A and constant regions of B into an single protein.
In regard to the preamble of the claim directed to the physiologically-regulated expression; of the membrane anchored and/or secreted antibody, it must be noted that Applicant’ specification provides no special definition for the phrase “physiologically-regulated expression” and therefore the Examiner has interpreted this phrase as the expression exhibited by a B cell in culture. Importantly, Endl demonstrates that when the B cell line is transfected with the above nucleic acid product, both secreted (black diamonds) and membrane bound (gray bars) antibodies are produced by the transfected B cells (see #3-5 of “pmIgG-A” of Fig. 3).
However, Endl is silent to a pseudotyped viral vector for transducing the B cells.
In regard to instant claim 22, Luo teaches a multicistronic nucleic acid encoding a light chain and heavy chain antibody, wherein the nucleic acid is in a pseudotyped lentiviral vector (p.1422, 1st para, p. 1424, 3rd para., see Fig. 1B). Note that Luo refers to their previous publication to evidence that the FUW lentiviral vector was pseudotyped with VSV glycoprotein.
Accordingly, it would have been obvious to one of ordinary skill in the art at the time of filing to have practiced a method of expressing membrane anchored and/or secreted antibodies in a multicistronic vector as suggested by Endl et al. and to substitute a lentiviral vector as taught by Luo with a reasonable expectation of success. The ordinary skilled artisan would have been motivated to do so as taught by Luo because the growth factors that promote B cell lineage also facilitate lentiviral transduction (p. 1424, 1st para.), and that stable integration of the lentivirus encoding the antibodies is maintained in antibody-secreting B cells (p. 1428, 2nd para.).
In regard to claim 28, Endl teaches the antibody may be a scFv (p. 16, last para.)
Hence, the claimed invention as a whole was prima facie obvious in the absence of evidence to the contrary.
Claims 27 and 33 are rejected under 35 U.S.C. 103 as being unpatentable over Endl et al., (WO2007/131774, filed 5/15/2007)
With respect to claim 27, Endl teaches a method for inducing the physiologically-regulated expression of a membrane-anchored and/or secreted antibody of interest by a B cell line ex vivo (e.g., Sp2/0-Ag14 cells), comprising by exposing the B cell to the “pmIgG-A” plasmid comprising:
A) a sequence encoding a heavy chain variable domain (VH) specifically interacting with an antigen of interest,
B2) a sequence encoding an effector protein comprising heavy constant regions CH1-CH3,
B3) a first intronic sequence comprising a secretory specific polyA sequence (polyAs) comprising an internal 5’ splice site enabling the splicing of the first intronic sequence and polyAs,
[AltContent: textbox ([img-media_image1.png])]B4) a second intronic sequence comprising a an internal 3’ splice site and the M1 and M2 domains of the heavy chain transmembrane and cytoplasmic domains, and
B5) a membrane specific polyA sequence (polyAm) after the M2 domain (p. 59, last para., p. 61, p. 63, lines 19-23, Figs. 1-3, but see modified Fig. 1A adjacent),
wherein the nucleic acid encodes the variable heavy chain regions of A and constant regions of B into an single protein.
In regard to the preamble of the claim directed to the physiologically-regulated expression; of the membrane anchored and/or secreted antibody, it must be noted that Applicant’ specification provides no special definition for the phrase “physiologically-regulated expression” and therefore the Examiner has interpreted this phrase as the expression exhibited by a B cell in culture. Importantly, Endl demonstrates that when the B cell line is transfected with the above nucleic acid product, both secreted (black diamonds) and membrane bound (gray bars) antibodies are produced by the transfected B cells (see #3-5 of “pmIgG-A” of Fig. 3).
In regard to claim 33, Endl teaches the antibody may be a scFv (p. 16, last para.). Note that in light of the preamble of Claim 33, and for the sake of compact prosecution, it is being interpreted as being dependent on the method of Claim 27.
Hence, the claimed invention as a whole was prima facie obvious in the absence of evidence to the contrary.
Claims 23-26 and 29-32 are rejected under 35 U.S.C. 103 as being unpatentable over Endl et al., (WO2007/131774, filed 5/15/2007), in view of Akamatsu et al., (US 7,732,195, filed 11/01/2007) and Aebischer-Gumy et al. (US2017/0350886, filed 3/02/2015, published 12/07/2017)
With respect to claims 23(ii)-26(ii), Endl teaches a methods for expression of a membrane-anchored and/or secreted antibody of interest by a host cell ex vivo, comprising by exposing the cell to the “pmIgG-A” plasmid comprising:
A) a sequence encoding a heavy chain variable domain (VH) specifically interacting with an antigen of interest,
B2) a sequence encoding heavy constant regions CH1-CH3,
B3) a first intronic sequence comprising a secretory specific polyA sequence (polyAs) comprising an internal 5’ splice site enabling the splicing of the first intronic sequence and polyAs,
[AltContent: textbox ([img-media_image1.png])]B4) a second intronic sequence comprising a an internal 3’ splice site and the M1 and M2 domaina of the heavy chain transmembrane and cytoplasmic domains, and
B5) a membrane specific polyA sequence (polyAm) after the M2 domain (p. 59, last para., p. 61, p. 63, lines 19-23, Figs. 1-3, but see modified Fig. 1A adjacent),
wherein the nucleic acid encodes the variable heavy chain regions of A and constant regions of B into an single protein.
However, in regard to Claims 23(ii)-26(ii), although Endle teaches the antibody expression vector is a plasmid, and generically discloses that the biologically active peptide is an immunoglobulin that causes a biological effect in vivo (p. 15, 1st para.), they are silent to using said plasmid vector to express an antibody in vivo so as to treat a disease such as cancer by providing vectored immunoprophylaxis against a tumor antigen.
Aebischer-Gumy teaches method for inducing the physiologically-regulated expression of membrane anchored and/or secreted antibodies comprising exposing a host cell to an expression vector encoding an antibody that is differentially spliced between membrane bound and secreted forms ([0010, 0013, 0073, 0131-0149, see also Fig.1). Specifically, in regard to claims 23(ii)-26(ii), Aebischer-Gumy teaches methods of using the antibody expression vector for the treatment of a disorder such as by gene therapy [147-0149]. Specifically in regard to Claim 26, Aebischer-Gumy teaches targeting tumor cells and provides a genus of tumor antigens [0121,0122].
Accordingly, it would have been obvious to one of ordinary skill in the art at the time of filing to have practiced an in vitro method of expressing membrane anchored and/or secreted antibodies in a B cell as suggested by Endl et al. and to substitute an in vivo method of expressing membrane anchored and/or secreted antibodies in a B cell to treat a disease as taught by Aebischer-Gumy with a reasonable expectation of success. The ordinary skilled artisan would have been motivated to do so as taught by Aebishcer-Gumy because this method circumvents the highly controlled process of antibody production by activated B cells in the human immune system ([0004], see also p. 3, 1st para. of Endl). In regard to choosing to treat cancer, as stated supra, Aebishcer-Gumy discloses several tumor antigen for which the antibodies can target, thereby providing a subject with immediate immunity against the cancer.
In regard to Claims 29-32, both Endl and Aebischer-Gumy teach the antibodies comprise scFv (p. 16, last para. of Endl, and see [0041-0042] of Aebischer-Gumy). Note that in light of the preamble of Claim 32, and for the sake of compact prosecution, it is being interpreted as being dependent on the method of Claim 26.
Hence, the claimed invention as a whole was prima facie obvious in the absence of evidence to the contrary.
RESPONSE TO ARGUMENTS
Applicant's arguments filed on 4/10/2026 are acknowledged.
Applicant argues that the claimed subject-matter is considered to be allowable over the cited prior art for the same reasons as the parent case. Furthermore, Applicant argues that unlike the parent case, instant claims are not restricted to a particular size introns between the CH3 and M1, nor between the M1 and M2 segments, and Applicant takes issue with the reasons for allowance of the parent case of an CH3/M1 intron between 350-380 nucleotides, and M1/M2 intron of 200-250 nucleotides, and that the patentability of instant claims in ability to express both the membrane and secreted forms of an heavy chain immunoglobulin.
Applicant's arguments have been fully considered but they are not persuasive.
In response to Applicant's arguments, 37 CFR § 1.111(b) states, "A general allegation that the claims define a patentable invention without specifically pointing out how the language of the claims patentably distinguishes them from the references does not comply with the requirements of this section." Applicant has failed to specifically point out how the language of the claims patentably distinguishes them from the references.
In regard to the preamble of the claim directed to the physiologically-regulated expression; of the membrane anchored and/or secreted antibody, it must be noted that Applicant’ specification provides no special definition for the phrase “physiologically-regulated expression” and therefore the Examiner has interpreted this phrase as the expression exhibited by a B cell in culture. Importantly, Endl demonstrates that when the B cell line is transfected with the above nucleic acid product, both secreted (black diamonds) and membrane bound (gray bars) antibodies are produced by the transfected B cells (see #3-5 of “pmIgG-A” of Fig. 3). Thus, the taught nucleic acid of Endl, which has all of the claimed elements, is capable of performing the function of secreting both membrane bound and secreted antibodies.
Terminal Disclaimer
The terminal disclaimer filed on 4/14/2026 disclaiming the terminal portion of any patent granted on this application which would extend beyond the expiration date of US Patent 11,623,950 has been reviewed and is accepted. The terminal disclaimer has been recorded.
Withdrawn Double Patenting
The prior rejection of Claims 22-33 on the grounds of nonstatutory double patenting over claims 1-11, 15-19 of U.S. Patent No. 11,623,950 (Fusil et al., Patented 4/11/2023) is withdrawn.
Conclusion
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 extension fee 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 date of this final action.
No claims are allowed.
Examiner Contact Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ARTHUR S LEONARD whose telephone number is (571)270-3073. The examiner can normally be reached on Mon-Fri 9am-5pm.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, James Doug Schultz can be reached on 571-272-0763. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/ARTHUR S LEONARD/Examiner, Art Unit 1631
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