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 .
Status of the Claims
Applicant’s submission filed 04 December 2025 has been entered. Claims 1-4, 7, 14, 19-28, 30, and 34-40 are pending. Claims 1, 26, 36, 38, and 40 have been amended. Therefore, prosecution on the merits continues for claims 1-4, 7, 14, 19-28, 30, and 34-40.
Status of Prior Rejections/Response to Arguments
RE: Objection to claims 26, 36, 38, and 40
Applicant’s amendments to each of instant claims 26, 36, 38, and 40 correct the minor informalities and thus obviate the objections of record.
Therefore, the objections are withdrawn.
RE: Rejection of claims 1-3, 7, 14, 19-28, 30, and 34-37 under 35 USC 112(b)
Applicant’s amendments to independent claim 1 removing the recitation of “plasmablasts” and “plasma cells” from the limitation in step (a) obviates the current rejection of record.
Therefore, the rejection is withdrawn.
RE: Rejection of claims 1-4, 7, 14, 19-23, 26-28, and 36 under 35 USC 103 over Scholz et al
Applicant's arguments filed 04 December 2025 have been fully considered but they are not
persuasive.
Applicant has traversed the rejection, asserting in Pages 7-11 of the Remarks filed 04 December 2025 that the ordinary artisan would not have been motivated to select the specific combination of factors given the disclosure of Scholz et al. With that, Applicant cites Ex Parte Gerlach, Appeal 2011-007057, in which it was decided that “[t]he mere fact that the prior art could be modified as proposed by the Examiner is not sufficient to establish a prima facie case of obviousness”, and emphasized that the Examiner must explain why the prior art would have provided the reason or suggestion to select the particular groups. In response, the Examiner respectfully submits that the requirements for a prima facie case of obviousness are detailed in the MPEP, as defined by Graham v. Deere and KSR, and that the rejection of record articulated those requirements. Applicant appears to point to Gerlach in an attempt to show that the rejection of record has not made a proper prima facie case of obviousness. However, Applicant has not articulated how the fact pattern in Ex Parte Gerlach (which is non-precedential) is relevant to the facts of the instant rejection of record. Further, Applicant has failed to recognize the precedential KSR decision from 2007, wherein the Supreme Court articulated that the “teaching, suggestion, or motivation” test is not the only valid standard for a prima facie rejection. Accordingly, MPEP § 2143.01(III) states that “[t]he mere fact that references can be combined or modified does not render the resultant combination obvious unless the results would have been predictable to one of ordinary skill in the art. KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398, 417, 82 USPQ2d 1385, 1396 (2007) (emphasis added). As applied to the instant case (and stated in the rejection), the ordinary artisan would have recognized that the activation and differentiation culture mediums can comprise the listed B cell activation factors, as Scholz et al disclose that the B cells may be contacted with any of a variety of cytokines or growth factors known to activate and/or differentiate B cells (Paragraph [0030]), and each of IL-2, IL-4, IL-10, IL-15, IL-21, soluble CD40L and a corresponding cross-linking enhancer are known to activate and/or differentiate B cells (Scholz et al: Paragraphs [0030]-[0035]). The disclosure of Scholz et al also provides no indication that the combination of factors would impart any unpredictable results when in contact with the B cells. Therefore, the precedence set forth by MPEP § 2143.01(III) provides a prima facie case of obviousness.
Applicant has further traversed the rejection, asserting in Page 12 of the Remarks filed 04 December 2025 that the Office’s reasoning must solely depend on impermissible hindsight to find that the instantly claimed combination of factors is obvious. In response, the Examiner respectfully submits that it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971). In the instant case, Scholz et al disclose the isolation of B cells from a whole blood or PBMC sample, culturing the B cells in a culture medium comprising B cell activating factors, transducing the cultured B cells with a transgene, and differentiating the transduced B cells into a plasma cell that expresses the transgene, wherein the transduced B cells are comprised within a culture medium comprising B cell activating factors (Paragraphs [0011]-[0014], [0020], [0022]-[0023], [0027], [0073]). With that, Scholz et al disclose that the B cell activating factors include IL-2, IL-4, IL-10, IL-15, IL-21, soluble CD40L and a corresponding cross-linking enhancer (Paragraphs [0030]-[0035]). Therefore, it would have been within the skillset of the ordinary artisan to arrive at the instantly claimed combination of factors given the disclosure of Scholz et al.
Applicant has lastly traversed the rejection, asserting in Page 12 of the Remarks filed 04 December 2025 that the instantly claimed method results in B cells having an unexpectedly increased level of proliferation and migration. Applicant supports these assertions with Examples 8-9 and Figures 13-15 of the instant disclosure. In response, the Examiner respectfully reminds Applicant that, in submitting evidence asserted to establish unobvious results, there is a burden on Applicant to indicate how the examples asserted to represent the claimed invention are considered to relate to the examples intended to represent the prior art and, particularly, to indicate how those latter examples do represent the closest prior art. The evidence relied upon should also be reasonably commensurate in scope with the subject matter claimed and illustrate the claimed subject matter relative to the prior art subject matter. See MPEP § 2145. It should also be established that the differences in the results are in fact unexpected and unobvious and of both statistical and practical significance. See MPEP § 716.02(b). In the instant case, Applicant has failed to indicate how the alleged unexpected results differ from the closest prior art, and has instead referenced pan-B cells cultured in various cytokine combinations to support the purported “unexpected results”. It is also of note that the cited examples are not commensurate in scope with the instantly claimed methods, as they are solely directed to the expansion – or steps (a)-(b) of instant claim 1 – of pan-B cells and do not indicate that the results are transferrable to the other claimed B cell types, nor how the transfection and differentiation of the cells – or steps (c)-(d) of instant claim 1 – is affected.
Therefore, the rejection is maintained.
RE: Rejection of claims 1-4, 7, 14, 19-24, 26-28, and 34-38 under 35 USC 103 over Scholz et al in view of Aronovich et al
Applicant's arguments filed 04 December 2025 have been fully considered but they are not
persuasive.
Applicant has traversed the rejection, citing the same assertions presented within Pages 7-12 of
the Remarks filed 04 December 2025 in regards to the rejection over Scholz et al. In response, the Examiner respectfully directs Applicant to the discussion of the 35 USC 103 rejection over
Scholz et al.
Therefore, the rejection is maintained.
RE: Rejection of claims 1-4, 7, 14, 19-24, 26-28, and 34-40 under 35 USC 103 over Scholz et al in view of Aronovich et al and Naito et al
Applicant's arguments filed 04 December 2025 have been fully considered but they are not
persuasive.
Applicant has traversed the rejection, citing the same assertions presented within Pages 7-12 of
the Remarks filed 04 December 2025 in regards to the rejection over Scholz et al. In response, the Examiner respectfully directs Applicant to the discussion of the 35 USC 103 rejection over
Scholz et al.
Therefore, the rejection is maintained.
RE: Rejection of claims 1-4, 7, 14, 19-23, 25-28, and 36 under 35 USC 103 over Scholz et al in view of Mayrhofer et al
Applicant's arguments filed 04 December 2025 have been fully considered but they are not
persuasive.
Applicant has traversed the rejection, citing the same assertions presented within Pages 7-12 of
the Remarks filed 04 December 2025 in regards to the rejection over Scholz et al. In response, the Examiner respectfully directs Applicant to the discussion of the 35 USC 103 rejection over
Scholz et al.
Therefore, the rejection is maintained.
RE: Rejection of claims 1-4, 7, 14, 19-23, 26-28, 30, and 36 under 35 USC 103 over Scholz et al in view of Caraux et al
Applicant's arguments filed 04 December 2025 have been fully considered but they are not
persuasive.
Applicant has traversed the rejection, citing the same assertions presented within Pages 7-12 of
the Remarks filed 04 December 2025 in regards to the rejection over Scholz et al. In response, the Examiner respectfully directs Applicant to the discussion of the 35 USC 103 rejection over
Scholz et al.
Therefore, the rejection is maintained.
RE: Provisional rejection of claims 1-4, 7, 14, 19-28, 30, and 34-40 over claims 14-20 of copending Application No. 18/949,362 in view of Scholz et al, Mayrhofer et al, Caraux et al, Aronovich et al, and Naito et al
Applicant has not specially traversed the rejection, instead asserting in Page 14 of the Remarks filed 04 December 2025 that the provisional nonstatutory double patenting rejection should be withdrawn since the instant application has an earlier patent term filing date than the copending application and would be the last rejection remaining. In response, the Examiner respectfully submits that, given the unpersuasive arguments as discussed above, the nonstatutory rejection is not the last remaining rejection.
Therefore, the rejection is maintained.
Maintained Grounds of Rejection
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.
Claims 1-4, 7, 14, 19-23, 26-28, and 36 remain rejected under 35 U.S.C. 103 as being unpatentable over Scholz et al (US 2013/0143267 A1, of record on IDS filed 30 November 2022).
Scholz et al is considered prior art under 35 USC 102(a)(1) and 35 USC 102(a)(2), with a publication date of 06 June 2013.
Regarding claims 1, 4, and 7: Scholz et al disclose compositions and methods for transducing B cells, wherein the transduced B cells are differentiated and express a transgene of interest (Abstract).
As such, Scholz et al disclose the isolation of B cells from a whole blood or PBMC sample, culturing the B cells in a culture medium comprising B cell activating factors, transducing the cultured B cells with a transgene, and differentiating the transduced B cells into a plasma cell that expresses the transgene, wherein the transduced B cells are comprised within a culture medium comprising B cell activating factors (Paragraphs [0011]-[0014], [0020], [0022]-[0023], [0027], [0073]). With that, Scholz et al disclose that the differentiated plasma cells – which are differentiated from the isolated B cells – do not express pan-B cell markers (Paragraphs [0007], [0028], [0036]).
Scholz et al further disclose that the B cell activating factors include IL-2, IL-4, IL-10, IL-15, IL-21, soluble CD40L and a corresponding cross-linking enhancer (Paragraphs [0030]-[0035]).
However, Scholz et al do not exemplify or reduce to practice a method of culturing and differentiating the B cells in culture medium comprising IL-2, IL-4, IL-10, IL-15, IL-21, soluble CD40L and a corresponding cross-linking enhancer, as required by instant claim 1.
Therefore, it would have been prima facie obvious to have modified the method of Scholz et al such that the culture medium comprised the B cell activating factors of IL-2, IL-4, IL-10, IL-15, IL-21, soluble CD40L and a corresponding cross-linking enhancer. One of ordinary skill in the art before the effective filing date of the invention would have recognized that the activation and differentiation culture medium can comprise the listed B cell activation factors, as Scholz et al disclose that the B cells may be contacted with any of a variety of cytokines or growth factors known to activate and/or differentiate B cells (Paragraph [0030]). Furthermore, the ordinary artisan would have had a reasonable expectation of success given that Scholz et al disclose protocols comprising the activation and differentiation culture mediums, and all the B cell activation factors. See MPEP § 2143(I)(G).
Consequently, Scholz et al render obvious a method of producing a modified B cell composition wherein B cells are isolated from a sample of whole blood or PBMCs (claim 7), cultured in a medium comprising IL-2, IL-4, IL-10, IL-15, IL-21, soluble CD40L and a corresponding cross-linking enhancer, transduced with a transgene, and differentiated into a plasma cell that expresses the transgene, wherein the differentiation culture medium comprises IL-2, IL-4, IL-10, IL-15, IL-21, soluble CD40L and a corresponding cross-linking enhancer. As Scholz et al disclose that differentiated plasma cells do not express pan-B cell markers, absent evidence to the contrary, the disclosure of Scholz et al reasonably suggests that the starting population of isolated B cells comprises pan-B cells. This therefore renders obvious the method of instant claims 1 and 4.
Regarding claims 2-3: Following the discussion of claim 1, Scholz et al further disclose that a gene encoding a marker protein may be placed before or after the transgene to allow for identification of cells that are expressing the desired protein (claim 2), wherein the marker proteins include a fluorescent marker protein and a drug resistance factors (claim 3) (Paragraphs [0052]-[0053], [0065]). This therefore reads on the method of the instant claims.
Regarding claim 14: Following the discussion of claim 1, Scholz et al further disclose that, in some embodiments, the transduced B cells may be cultured on feeder cells (Paragraphs [0030]-[0031]). As this indicates that there are embodiments of the invention wherein the transduced cells are not cultured on feeder cells, this therefore reads on the method of the instant claim.
Regarding claims 19-21: Following the discussion of claim 1, Scholz et al further disclose that the B cells are transduced with a lentiviral vector (claims 19-21) (Paragraphs [0011], [0014], [0044]-[0046], [0068]). This therefore reads on the method of the instant claims.
Regarding claims 22-23: Following the discussion of claim 19, Scholz et al further disclose that the viral vector is typically cloned into a plasmid (claims 22-23) (Paragraphs [0047], [0053], [0070], [0072], [0094]-[0096]). This therefore reads on the method of the instant claims.
Regarding claims 26-28: Following the discussion of claim 1, Scholz et al further disclose that the transgene encodes an antigen-specific antibody or antigen-binding fragment thereof (claim 26) – wherein the antibody is an anti-HIV antibody (claim 28) – or a cell surface receptor, a secreted protein, or an adhesion molecule (claim 27) (Paragraphs [0011], [0075]-[0076], [0081]-[0082]). This therefore reads on the methods of the instant claims.
Regarding claim 36: Following the discussion of claim 1, Scholz et al further disclose that a therapeutically effective amount of the differentiated B cells are administered to a subject in need thereof (Paragraphs [0017], [0106]-[0108]). This therefore reads on the method of the instant claim.
Claims 1-4, 7, 14, 19-24, 26-28, 34-38, and 40 remain rejected under 35 U.S.C. 103 as being unpatentable over Scholz et al (US 2013/0143267 A1, of record on IDS filed 30 November 2022) in view of Aronovich et al (Human Molecular Genetics, 2011, of record).
The discussion of Scholz et al in regards to claims 1, 19, 22-23, and 36 can be observed above and is relied upon herein, the content of which is incorporated in its entirety. Scholz et al render obvious claims 1-4, 7, 14, 19-23, 26-28, and 36. Aronovich et al is considered prior art under 35 USC 102(a)(1).
Regarding claim 24: As aforementioned in the discussion of claim 23 above, Scholz et al disclose that the B cells are transduced with a lentiviral vector that has been cloned into a plasmid.
Scholz et al further disclose that the B cells may be transduced using any known technique in the art, including electroporation (Paragraph [0105]).
Scholz et al do not disclose that the B cells are transduced via electroporation with a transposon that comprises the transgene, as required by instant claim 24.
Aronovich et al, however, disclose that the Sleeping Beauty (SB) transposon system is the leading nonviral vector for gene therapy (Abstract). Aronovich further disclose that the SB transposon system is delivered into a cell via electroporation (Page R17, Column 1; Figure 2).
Therefore, it would have been prima facie obvious to substitute the lentiviral vector and plasmid system of Scholz et al with the SB transposon system of Aronovich et al, as doing so would be a simple substitution of one vector system for another. See MPEP § 2143(I)(B). One of ordinary skill in the art before the effective filing date of the invention would have recognized that the two vector systems are functionally comparable, as the SB transposon system yielded similar results to viral vectors (Aronovich et al: Page R16, Delivery in vivo to the liver…), and would have thereby been able to substitute the vector systems with predictable results.
Consequently, Scholz et al as modified by Aronovich et al render obvious a method of producing a modified B cell composition, wherein the B cells are electroporated with the SB transposon system. This therefore renders obvious the method of the instant claim.
Regarding claims 34-35, 37-38, and 40: Following the discussion of claims 1, 24 and 36, Scholz et al further disclose that the transduced B cells can be used in the treatment or prevention of various infectious diseases, cancers, degenerative diseases, and immunological disorders (Paragraph [0116]).
Scholz et al do not disclose the treatment of mucopolysaccharidosis type I, wherein the B cells are electroporated with a transposon system that comprises the transgene of iduronidase, as required by claims 34 and 38.
Aronovich et al, however, disclose that the SB transposon system is utilized in the treatment of mucopolysaccharidosis type I (MPS I), wherein iduronidase (IDUA) is delivered to the subject in need thereof (Pages R16-R17, Delivery in vivo to the liver…).
Therefore, it would have been prima facie obvious to modify the method of Scholz et al such that the B cells are electroporated with a SB transposon system comprising a IDUA transgene for the treatment of MPS 1, as suggested in Aronovich et al. One of ordinary skill in the art before the effective filing date of the invention would have been motivated to treat MPS I utilizing a cell therapy technique that is well-known in the art, and would have had a reasonable expectation of success given the transduction and treatment protocols outlined in Scholz et al (Paragraphs [0017], [0105]-[0108]) coupled with the disclosure of Aronovich et al detailing the SB transposon system (Pages R15-R17). See MPEP § 2143(I)(G).
Consequently, Scholz et al as modified by Aronovich et al render obvious a method of producing a modified B cell composition, wherein pan-B cells are isolated from a sample, cultured in a medium comprising IL-2, IL-4, IL-10, IL-15, IL-21, soluble CD40L and a corresponding cross-linking enhancer, electroporated with a sleeping beauty transposon system (claim 35) comprising an iduronidase transgene (claim 34), differentiated into a plasma cell within culture medium comprising IL-2, IL-4, IL-10, IL-15, IL-21, soluble CD40L and a corresponding cross-linking enhancer, and administered in a therapeutically effective amount to a subject suffering from MPS I (claims 37 and 40). This therefore renders obvious the method of instant claim 38.
Claims 1-4, 7, 14, 19-24, 26-28, and 34-40 remain rejected under 35 U.S.C. 103 as being unpatentable over Scholz et al (US 2013/0143267 A1, of record on IDS filed 30 November 2022) in view of Aronovich et al (Human Molecular Genetics, 2011, of record) and Naito et al (Cancer Immunol Immunother, 2013, of record).
The discussion of Scholz et al regarding claims 1, 19, 22-23, and 36 can be observed above and is relied upon herein, the content of which is incorporated in its entirety. In addition, the discussion of Scholz et al in view of Aronovich et al regarding claim 38 can be observed above and is relied upon in its entirety. Scholz et al render obvious claims 1-4, 7, 14, 19-23, 26-28, and 36. Scholz et al in view of Aronovich et al render obvious claims 1-4, 7, 14, 19-24, 26-28, 34-38, and 40. Naito et al is considered prior art under 35 USC 102(a)(1).
Regarding claim 39: As aforementioned in the discussion of claim 38, Scholz et al as modified by Aronovich et al render obvious a method of producing a modified B cell composition, wherein pan-B cells are isolated from a sample, cultured in a medium comprising IL-2, IL-4, IL-10, IL-15, IL-21, soluble CD40L and a corresponding cross-linking enhancer, electroporated with a sleeping beauty transposon system comprising an iduronidase transgene, and differentiated into a plasma cell within culture medium comprising IL-2, IL-4, IL-10, IL-15, IL-21, soluble CD40L and a corresponding cross-linking enhancer.
Neither the disclosure of Scholz et al nor Aronovich et al teach that the soluble CD40L is soluble CD40L that is histidine-tagged and the corresponding cross-linking enhancer is an anti-poly-histidine monoclonal antibody, as required by instant claim 39.
Naito et al, however, disclose that soluble human recombinant histidine-tagged CD40L cross-linked with monoclonal antibodies against the amino-terminal epitope tags (HexaHis) are well-known B cell activation factors (Page 349, Other CD40L formulations; Page 351, Stimulation of B cells…).
Therefore, it would have been prima facie obvious to substitute the soluble CD40L and corresponding cross-linking enhancer of Scholz et al with the soluble CD40L-his cross-linked with an anti-HexaHis monoclonal antibody of Naito et al, as doing so would be a simple substitution of one soluble CD40L and cross-linking enhancer for another. See MPEP § 2143(I)(B). One of ordinary skill in the art before the effective filing date of the invention would have recognized that the two B cell activation factors are functionally comparable, and would have thereby been able to substitute the factors with predictable results.
Consequently, Scholz et al as modified by Aronovich et al and Naito et al render obvious a method of producing a modified B cell composition, wherein the B cells are cultured in mediums comprising IL-2, IL-4, IL-10, IL-15, IL-21, and soluble CD40L-his cross-linked with an anti-HexaHis monoclonal antibody. This therefore renders obvious the method of the instant claim.
Claims 1-4, 7, 14, 19-23, 25-28, and 36 remain rejected under 35 U.S.C. 103 as being unpatentable over Scholz et al (US 2013/0143267 A1, of record on IDS filed 30 November 2022) in view of Mayrhofer et al (Humana Press, 2009, of record).
The discussion of Scholz et al in regards to claims 1, 19, and 22-23 can be observed above and is relied upon herein, the content of which is incorporated in its entirety. Scholz et al render obvious
claims 1-4, 7, 14, 19-23, 26-28, and 36. Mayrhofer et al is considered prior art under 35 USC 102(a)(1).
Regarding claim 25: As aforementioned in the discussion of claim 23 above, Scholz et al disclose that the B cells are transduced with a lentiviral vector that has been cloned into a plasmid.
Scholz et al further disclose that the B cells may be transduced using any known technique in the art (Paragraph [0105]).
Scholz et al do not disclose that the B cells are transduced with a minicircle, a mini-intronic plasmid, or a nanoplasmid, as required by instant claim 25.
Mayrhofer et al, however, disclose the transfection of cells in vitro with minicircle vectors, wherein the transfection results in an improved expression of the transgenes within the cell (Pages 95, 98-101).
Therefore, it would have been prima facie obvious to modify the method of Scholz et al such that the transgene is comprised within a minicircle vector, as detailed in Mayrhofer et al. One of ordinary skill in the art before the effective filing date of the invention would have been motivated to utilize a vector system that requires less plasmid DNA and transfection reagent while having an enhanced transgene expression, and would have had a reasonable expectation of success based on the disclosure of Mayrhofer et al. See MPEP § 2143(I)(G).
Consequently, Scholz et al as modified by Mayrhofer et al render obvious a method of producing a modified B cell composition, wherein the B cells are transduced with a minicircle vector comprising the transgene. This therefore renders obvious the method of the instant claim.
Claims 1-4, 7, 14, 19-23, 26-28, 30, and 36 remain rejected under 35 U.S.C. 103 as being unpatentable over Scholz et al (US 2013/0143267 A1, of record on IDS filed 30 November 2022) in view of Caraux et al (Hematologica, 2010, of record).
The discussion of Scholz et al regarding claim 1 can be observed above and is relied upon herein, the content of which is incorporated in its entirety. Scholz et al render obvious claims 1-4, 7, 14, 19-23,
26-28, and 36. Caraux et al is considered prior art under 35 USC 102(a)(1).
Regarding claim 30: Following the discussion of claim 1, Scholz et al further disclose that the differentiated plasma cells express CD38 and CD138 but lack expression of CD20 (Paragraphs [0007], [0013], [0028], [0036]).
Scholz et al do not disclose that at least 20% of the plasma cells are CD20-, CD38+, and CD138-, as required by instant claim 30.
Caraux et al, however, disclose circulating plasma cells can be either CD138+ or CD138-, wherein about 57% of the circulating plasma cells are CD138- and the remaining 43% are CD138+ (Abstract; Pages 1019-1020 ; Figure 1).
Therefore, it would have been prima facie obvious to have modified the method of Schultz such that at least 20% of the plasma cells are instead CD138-, as the ordinary artisan would have been motivated to differentiate the B cells into plasma cells having the more prevalent phenotype within the human body. One of ordinary skill in the art before the effective filing date of the invention would have had a reasonable expectation of success due to the differentiation protocols outlined in Scholz et al coupled with the CD138- plasma cell features and expression profiles outlined in Caraux et al. See MPEP § 2143(I)(G).
Consequently, Scholz et al as modified by Caraux et al render obvious a method of producing a modified B cell composition, wherein at least 20% of the differentiated plasma cells are CD20-, CD38+, and CD138-. This therefore renders obvious the method of the instant claim.
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 1-4, 7, 14, 19-28, 30, and 34-40 remain provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 14-20 of copending Application No. 18/949,362 in view of Scholz et al (US 2013/0143267 A1, of record on IDS filed 30 November 2022), Mayrhofer et al (Humana Press, 2009, of record), Caraux et al (Hematologica, 2010, of record), Aronovich et al (Human Molecular Genetics, 2011, of record), and Naito et al (Cancer Immunol Immunother, 2013, of record).
Although the claims at issue are not identical, they are not patentably distinct from each other because the copending claims render obvious the instant claims. More specifically, the copending claims are not identical because no single copending claim discloses all of the limitations of any of the instant claims; however, each of the limitations of the instant claims are rendered obvious by the accompanying prior art.
Copending claim 14 is directed to a method of producing a population of modified differentiated B cells, the method comprising:
(a) isolating pan-B cells, memory B cells, switch memory B cells, plasmablasts, or plasma cells from a sample, thereby obtaining an isolated B cell population;
(b) culturing the isolated B cell population in vitro with one or more B cell activating factors, thereby obtaining an expanded B cell population;
(c) transfecting or transducing the expanded B cell population with a gene encoding an scFv; and
(d) differentiating the expanded B cell population in vitro with one or more B cell activating factors, thereby obtaining a modified differentiated B cell composition.
Copending claim 14 does not disclose the specific B cell activating factors.
Scholz et al, however, disclose that the B cell activating factors include IL-2, IL-4, IL-10, IL-15, IL-21, soluble CD40L and a corresponding cross-linking enhancer (Paragraphs [0030]-[0035]).
It therefore would have been prima facie obvious to have modified the method of copending claim 14 such that the B cell activating factors include IL-2, IL-4, IL-10, IL-15, IL-21, soluble CD40L and a corresponding cross-linking enhancer, as a person of ordinary skill in the art before the effective filing date of the invention would have been motivated to activate the B cells with known activation factors. This therefore renders obvious the method of instant claims 1, 4, and 26-27, as an scFv is considered an antigen-binding fragment and antigenic fragment.
Copending claims 15-16 are exactly or substantially identical to instant claims 2-3, respectively.
Copending claim 17 is substantially identical to instant claim 19.
Copending claims 18-19 are exactly or substantially identical to instant claims 22-24.
Furthermore, although the copending application does not disclose the limitations from instant claims 7, 14, 20-21, 25, 28, 30, and 34-40, the subject matter is known from the prior art and can be further incorporated into the method rendered obvious by copending claim 14 and Scholz et al:
Scholz et al teach the limitations of instant claims 7, 14, 20-21, 28, and 36.
Mayrhofer et al teach the limitation of instant claim 25.
Caraux et al teach the limitation of instant claim 30.
Copending claim 20 coupled with Aronovich et al teach the limitations of instant claims 34-35, 37-38, and 40.
Naito et al teach the limitation of instant claim 39.
This is a provisional nonstatutory double patenting rejection.
Conclusion
THIS ACTION IS MADE FINAL. 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.
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/ALYSSA G WESTON/Examiner, Art Unit 1633
/CHRISTOPHER M BABIC/Supervisory Patent Examiner, Art Unit 1633