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 .
DETAILED ACTION
Claim status
Claims 22-33 are pending
Claims 22-33 are under examination
Information Disclosure Statement
No information disclosure statement (IDS) has been submitted.
Furthermore, Applicant is reminded that the listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
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 Akamatsu et al., (US 7,732,195, filed 11/01/2007) and 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:
A1) & A2) a light chain kappa variable domain an antibody (V-kappa) fused in frame to the constant region of the light chain of the antibody (C-kappa); and
B1) & B2) a sequence encoding a heavy chain variable domain (VH) fused in frame to the heavy constant regions in secretory form (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).
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, although Endl does teach that the taught nucleic acid can be used to express heterologous immunoglobulins comprising light chains and heavy chains (p. 22, last para., p. 27, 3rd para., p. 29, 1st para.), and Endl does teach combining another nucleic acid encoding a light chain with the taught nucleic acid (p. 23, lines 23-25, p. 24, lines 9-15), and Endl discloses the use of an IRES linking sequence (p. 10, 2nd para.), they are silent with a multicistronic nucleic acid.
[AltContent: textbox ([img-media_image2.png])]With respect to instant claim, Akamatsu teaches a multcistronic nucleic acid comprising A1& A2) a sequence comprising a light chain variable region fused in frame with a sequence comprising light chain constant region (i.e., VL-C), and IRES linking sequence, and B1& B2) a sequence comprising a heavy chain variable region fused in frame with a heavy chain constant region (i.e., VH-CH) (see excerpt of Fig. 1 of Akamatsu adjacent), wherein the VL-C and VH-CH. These VL-C and VH-CH sequences are coexpressed as separate proteins that form an immunoglobulin, but also for the first and second subunits of an IgG (see Example 1).
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 comprising a nucleic acid encoding a immunoglobulin comprising a light chain and heavy chain as suggested by Endl and to combine the light chain and heavy chain into a single multicistronic nucleic acid as taught by Akamatsu with a reasonable expectation of success. The ordinary skilled artisan would have been motivated to do so as taught by Akamastu because an IRES allows the light chains and heavy chains to be controlled by a single promoter and ensures equivalent expression levels (col 7, lines 30-35, col 17 lines 30-40).
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), in view of Akamatsu et al., (US 7,732,195, filed 11/01/2007).
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:
A1) & A2) a light chain kappa variable domain an antibody (V-kappa) fused in frame to the constant region of the light chain of the antibody (C-kappa); and
B1) & B2) a sequence encoding a heavy chain variable domain (VH) fused in frame to the heavy constant regions in secretory form (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).
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, although Endl does teach that the taught nucleic acid can be used to express heterologous immunoglobulins comprising light chains and heavy chains (p. 22, last para., p. 27, 3rd para., p. 29, 1st para.), and Endl does teach combining another nucleic acid encoding a light chain with the taught nucleic acid (p. 23, lines 23-25, p. 24, lines 9-15), and Endl discloses the use of an IRES linking sequence (p. 10, 2nd para.), they are silent with a multicistronic nucleic acid.
[AltContent: textbox ([img-media_image2.png])]With respect to instant claim, Akamatsu teaches a multcistronic nucleic acid comprising A1& A2) a sequence comprising a light chain variable region fused in frame with a sequence comprising light chain constant region (i.e., VL-C), and IRES linking sequence, and B1& B2) a sequence comprising a heavy chain variable region fused in frame with a heavy chain constant region (i.e., VH-CH) (see excerpt of Fig. 1 of Akamatsu adjacent), wherein the VL-C and VH-CH. These VL-C and VH-CH sequences are coexpressed as separate proteins that form an immunoglobulin, but also for the first and second subunits of an IgG (see Example 1).
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 comprising a nucleic acid encoding a immunoglobulin comprising a light chain and heavy chain as suggested by Endl and to combine the light chain and heavy chain into a single multicistronic nucleic acid as taught by Akamatsu with a reasonable expectation of success. The ordinary skilled artisan would have been motivated to do so as taught by Akamastu because an IRES allows the light chains and heavy chains to be controlled by a single promoter and ensures equivalent expression levels (col 7, lines 30-35, col 17 lines 30-40).
In regard to claim 33, 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 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 23-26, 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:
A1) & A2) a light chain kappa variable domain an antibody (V-kappa) fused in frame to the constant region of the light chain of the antibody (C-kappa); and
B1) & B2) a sequence encoding a heavy chain variable domain (VH) fused in frame to the heavy constant regions in secretory form (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).
However, although Endl teaches that the taught nucleic acid can be used to express heterologous immunoglobulins comprising light chains and heavy chains (p. 22, last para., p. 27, 3rd para., p. 29, 1st para.), and Endl does teach combining another nucleic acid encoding a light chain with the taught nucleic acid (p. 23, lines 23-25, p. 24, lines 9-15), and Endl discloses the use of an IRES linking sequence (p. 10, 2nd para.), they are silent with a multicistronic nucleic acid.
[AltContent: textbox ([img-media_image2.png])]With respect to instant claims, Akamatsu teaches a multcistronic nucleic acid comprising A1& A2) a sequence comprising a light chain variable region fused in frame with a sequence comprising light chain constant region (i.e., VL-C), and IRES linking sequence, and B1& B2) a sequence comprising a heavy chain variable region fused in frame with a heavy chain constant region (i.e., VH-CH) (see excerpt of Fig. 1 of Akamatsu adjacent), wherein the VL-C and VH-CH. These VL-C and VH-CH sequences are coexpressed as separate proteins that form an immunoglobulin, but also for the first and second subunits of an IgG (see Example 1).
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 cell comprising a nucleic acid encoding a immunoglobulin comprising a light chain and heavy chain as suggested by Endl and to combine the light chain and heavy chain into a single multicistronic nucleic acid as taught by Akamatsu with a reasonable expectation of success. The ordinary skilled artisan would have been motivated to do so as taught by Akamastu because an IRES allows the light chains and heavy chains to be controlled by a single promoter and ensures equivalent expression levels (col 7, lines 30-35, col 17 lines 30-40).
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 cell as suggested by Endl et al. and to substitute an in vivo method of expressing membrane anchored and/or secreted antibodies in a 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 produc tion 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)
Hence, the claimed invention as a whole was prima facie obvious in the absence of evidence to the contrary.
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 obviousness-type 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); and 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 a nonstatutory double patenting ground provided the conflicting application or patent either is shown to be commonly owned with this application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement.
Effective January 1, 1994, a registered attorney or agent of record may sign a terminal disclaimer. A terminal disclaimer signed by the assignee must fully comply with 37 CFR 3.73(b).
Claims 22-33 are rejected 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).
The subject matter claimed in the instant application is fully disclosed in the referenced patent as follows: the methods for inducing a physiologically-regulated expression of a membrane or secreted antibody, methods for treating disease and prophylaxis of cited patent anticipates the methods of instant application. It is clear that all the elements of the cited patent claims are to be found in instant claims. The difference between the cited patent claims and the instant claims lies in the fact that the cited patent claims are much more specific with respect to the intron spacing. Thus the invention of said claims of the cited patent are in effect “species” of the “generic” invention of the instant claim. It has been held that the generic invention is “anticipated” by the “species”. See In re Goodman, 29 USPQ2d 2010 (Fed. Cir. 1993).
Since the instant application claims are anticipated by cited patent claims, said claims are not patentably distinct.
Conclusion
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