DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 06/20/2025 has been entered.
Applicant’s amendments to the claims and arguments filed on June 20, 2025 have been received and entered. Claims 1-3 have been amended, while claims 4-5, 9-12 have been canceled. Claims 14-16 are newly added. Claims 1-3, 6-8, 13-16 are pending in the instant application.
Priority
This application is a Divisional of US non-provisional application 15/559,080 09/18/2017, which is a 371 of PCT/FI16/50164 filed on 03/17/2016.
Claims 1-3, 6-8, 13-15 and 16 are under consideration.
Claim Objections
Claim 1 is objected for minor informalities as it contains syntax error. In the instant case, recitation of phrase “administering intravenously in an amount of 1x108-1x1014 virus particles to the subject an oncolytic adenoviral vector” should be replaced with phrase -- intravenously administering about 1x108 to 1x1014 virus particles of an oncolytic adenoviral vector to the subject -- Appropriate correction is required.
New-Claim Rejections - 35 USC § 112- necessitated by amendments
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 6 and 8 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. In the instant case, method of claims 6 and 8 limit the method 2, wherein adoptive cell therapeutic composition to a subject conducted simultaneously or consecutively or increases the efficacy of adoptive cell therapy, however method of claim 2 does not require administration of any adoptive cell therapeutic composition. Therefore, method of claims 6 and 8 do not further limit the method of claim 2. It is suggested that claims 6 and 8 should depend from claim 3. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Withdrawn-Claim Rejections - 35 USC § 103
Claims 1-12 and 13 were rejected under 35 U.S.C. 103 as being unpatentable over Song et al (WO/2014/138314, dated 09/12/2014, EFD03/05/2013, IDS) and Hemminki et al (WO2014/170389, 10/23/2014, IDS)/ Diaconu et al (WO/2012/038607, dated 3/29/2012, IDS). Upon further consideration and in view of applicant’s amendments to the claim introducing a dose range of the oncolytic virus against specific cancer type, previous rejection of claims are hereby withdrawn. Applicants’ arguments with respect to the withdrawn rejections are thereby rendered moot. The claims are however subject to new rejections over the prior art of record, as set forth below.
Claims 1-12 and 13 were rejected under 35 U.S.C. 103 as being unpatentable over Song et al (WO/2014/138314, dated 09/12/2014, EFD03/05/2013), Yu et al (Molecular Therapy, 2013, 1-10, IDS) and Diaconu et al (WO/2012/038607, dated 3/29/2012, IDS). The rejection is withdrawn for the reasons discussed above.
New-Claim Rejections - 35 USC § 103-in modified form
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.
Claims 1-3, 6-8, 13-15 and 16 are rejected under 35 U.S.C. 103 as being unpatentable over Hemminki et al (WO2014/170389, 10/23/2014, IDS), Song et al (WO/2014/138314, dated 09/12/2014, EFD03/05/2013, IDS) and Yoshida et al (Cancer Immunol Immunother (2003) 52: 97–106).
With respect to claim 1, 14-16, Hemminki teaches a method of treating cancer including lung, pancreatic or breast cancer in a subject (see page 25, lines 25-35) using an oncolytic adenoviral vector for increasing the efficacy of adoptive cell therapy or T cell therapy in the subject (see 4, lines 22-24) intravenously and intratumorally administering (see page 28, line 23) an adenoviral vector an effective amount of about 1x108-1x1014 vp (see page 28, lines 29-30) of a composition comprising : i) an adenovirus serotype 5 (Ad5) nucleic acid backbone comprising a 5/3 chimeric fiber knob; iil) |anE2F1 promoter for tumor specific expression of E1A; ill) a 24 bp deletion (D24) in the Rb binding constant region 2 of 10 adenoviral E1; iv) a nucleic acid sequence deletion of viral go79k and 6. 7k reading frames; and v) a nucleic acid encoding one cytokine in the place of the deleted go79k and 6.7k nucleic acid sequence in the 15 ES8region, 1) an adenovirus serotype 5 (Ad5) nucleic acid backbone comprising a 5/3 chimeric fiber knob: 2) E2F1 promoter for tumor specific expression of E1A; 3) a 24 bp deletion (D24) in the Rb binding constant region 2) of adenoviral E1; 4) a nucleic acid sequence deletion of viral gp19k and 6. 7k reading frames; and 5) a nucleic acid sequence encoding at least one cytokine transgene in the place of the deleted gp19k/6. 7K in the E3 region resulting in replication-associated control of transgene expression under the viral E3 promoter, wherein the cytokine is, IL-2, TNF alpha CD40L (see claims 12-13 of ‘389, page 5, lines 1-26). It is further disclosed that in another embodiment of the invention E3 gp19k/6.7k is kept in the vector but one or many other E3 areas have been deleted (e.g. E3 9-kDa, E3 10.2 kDa, E3 15.2 kDa and/or E3 15.3 kDa) (see page 19, lines 15-17) (limitation of claim 1).
PNG
media_image1.png
200
400
media_image1.png
Greyscale
Regarding claim 3, Hemminki teaches a method of treating cancer in a subject, wherein the method comprises separate administration of adoptive cell therapeutic composition and oncolytic adenoviral vectors coding for at least one cytokine to a subject as set forth above. (see claim 1 of ‘389), wherein the cell type selected from a group consisting of a tumor infiltrating lymphocyte (TIL), T-cell receptor modified lymphocytes and chimeric antigen receptor modified lymphocytes (see claim 3 of ‘389). It is further disclosed that the adoptive cell therapeutic composition comprises a cell type selected from a group consisting of T-cells, CD8+ cells, CD4+ cells, NK-cells, delta-gamma T-cells, regulatory T- cells, and peripheral blood mononuclear cells (see claim 4 of ‘389). Hemminki further teaches that the adoptive cell therapeutic composition comprises T-cells (see claim 5 of ‘389).
Regarding claim 6, Hemminki teaches that the administration(s) of adoptive cell therapeutic composition and oncolytic viral vectors to a subject is(are) conducted simultaneously or consecutively, in any order (see clam 8 of ‘389).
With respect to claim 7, Song teaches that method may include the step of delivering to the individual an additional, radiation, chemotherapy (see page 15, line 25).
With respect to claim 8, Hemminki teaches that method of delivering oncolytic adenoviral vector is used in increasing the efficacy of adoptive cell therapy or T-cell therapy in a subject (see page 4, lines 22-24).
Hemminki differs from claimed invention by not disclosing that the (1) oncolytic adeno virus is comprising: v) a nucleic acid sequence encoding a bispecific monoclonal antibody in the place of the deleted gp19k and 6.7k nucleic acid sequence in the E3 region (limitation of claim 1).
Regarding claim 1, Song teaches a method of treating an individual with cancer that includes lung cancer, comprising the step of intravenously or intratumorally (para. 5) delivering to the individual a therapeutically effective amount of an oncolytic adenovirus or vaccinia virus that encodes a bipartite molecule comprising a single chain variable fragment (scFv) specific for a cell surface molecule and a scFv specific for a tumor antigen (claim 1 of ‘314), preferably wherein the cell surface molecule is on T lymphocytes (claim 3 of ‘314) or is a CD3 (claim 6 of ‘314), and wherein the tumor antigen is selected from the group consisting of or Muc1 (para. 6, 8, 16, claim 4-5 of ‘314) (limitation of claims 1, 10-11). Song teaches that T cell engager-armed oncolytic virus, facilitates T cell infiltration in tumors and, through the virally-expressed T cell engager, induces bystander killing of tumor cells that are not infected by the virus, leading to an enhanced antitumor effect (see para. 7). The use of combination of bispecific antibodies (BsAb), i.e. anti-MUC1·anti-CD3 is known to enhance tumor growth inhibition by T-LAK cells against MUC1-expressing tumor cells as evident from the teaching of Yoshida (see page 97, col. 2, para. 1).
With respect to claim 12-13, Song continues to teach engager additionally comprises one or more of cytokine, a costimulatory domain, a domain that inhibits negative regulatory molecules of T-cell activation, or a combination thereof. In specific embodiments, wherein the cytokine is IL-2, and/or IL-7 (para. 49) (limitation of claims 12-13).
Therefore, it would have been prima facie obvious for a person of ordinary skill to combine the teachings of prior art to modify the method of treating cancer in a subject by substituting cytokine transgene on the oncolytic adenoviral vector in the place of a deletion in the E3 region as suggested in the oncolytic virus disclosed in Hemminki with another transgene encoding a bispecific antibody comprising a single chain variable region fragment directed against a cell surface molecule and an scFv specific against a tumor antigen as disclosed in Song, with a reasonable expectation of success, before the effective filing date of the instant invention.. Said modification amounting to combining prior art elements according to known methods to yield predictable results. One of ordinary skill in the art would be motivated to do so because (i) the cDNA coding for transgene placed into a gp19k/6. 7k deleted E3 region, under the E3 promoter restricts transgene expression to tumor cells that allow replication of the virus (see page 15, lines 25-28) and (ii) bispecific antibodies (BsAb) expression of anti-MUC1·anti-CD3 is known to enhance tumor growth inhibition by T-LAK cells against MUC1-expressing tumor cells (see above). One of skill in the art would have been expected to have a reasonable expectation of success because prior art successfully reported insertion of a heterologous coding sequence in the deleted E3 region of an Ad5/3 vector as evident from the teaching of Hemminki and prior art has successfully reported incorporated bipartite molecule comprising a single chain variable fragment (scFv) specific for a cell surface molecule and a scFv specific for a tumor antigen in an oncolytic virus. It should be noted that the KSR case forecloses the argument that a specific teaching, suggestion, or motivation is required to support a finding of obviousness See the recent Board decision Ex parte Smith, --USPQ2d--, slip op. at 20, (Bd. Pat. App. & Interf. June 25, 2007) (citing KSR, 82 USPQ2d at 1396) (available at http: www. uspto.gov/web/offices/dcom/bpai/prec/fd071925.pdf).
Claims 1-3, 6-8, 13-15 and 16 are rejected under 35 U.S.C. 103 as being unpatentable over Diaconu et al (WO/2012/038607, dated 3/29/2012, IDS), Song et al (WO/2014/138314, dated 09/12/2014, EFD03/05/2013, IDS) and Yoshida et al (Cancer Immunol Immunother (2003) 52: 97–106) and Yu et al (Molecular Therapy, 2013, 1-10, IDS).
Regarding 1, 14-16, Diaconu teaches a method treating cancer including lung, pancreatic or breast cancer (see page 19, lines 19-page 20, line 1-5), said method comprising intravenously administering about 108 to 1014 viral particle (see page 21, line 1) of an oncolytic adenoviral vector comprising 1) an adenovirus serotype 5 (Ad5) nucleic acid backbone comprising a 5/3 chimeric fiber knob: 2) a promoter for tumor specific expression of E1A; 3) a 24 bp deletion (D24) in the Rb binding constant region 2) of adenoviral E1; 4) a nucleic acid sequence deletion of viral gp19k and 6. 7k reading frames; and 5) a nucleic acid sequence encoding at least one hCDl40 in the place of the deleted gp19k/6. 7K in the E3 region resulting in replication-associated control of transgene expression under the viral E3 promoter, wherein the cytokine is, IL-2, TNF alpha CD40L. It is further disclosed that method may further comprise administration of oncolytic virus intratumorally (see page 21, line 26, claims 1-2 and figure 1A of ‘607, example 8).
With respect to claim 7, Diaconu teaches that method may include the step of delivering to the individual an additional cancer therapy, such as surgery, radiation, chemotherapy, immunotherapy, hormone therapy, or a combination thereof (see page 22, line 25).
Diaconu differs from claimed invention by not disclosing 1) v) a nucleic acid sequence encoding a bispecific monoclonal antibody in the place of the deleted gp19k and 6.7k nucleic acid sequence in the E3 region (limitation of claim 1) and method further comprising administration of adoptive T- cell therapeutic composition to the subject (limitation of claim 3).
Song cure the deficiency by teaching a method of treating an individual with cancer, comprising the step of intravenously or intratumorally (para. 5) delivering to the individual a therapeutically effective amount of an oncolytic adenovirus or vaccinia virus that encodes a bipartite molecule comprising a single chain variable fragment (scFv) specific for a cell surface molecule and a scFv specific for a tumor antigen (claim 1 of ‘314), preferably wherein the cell surface molecule is on T lymphocytes (claim 3 of ‘314) or is a CD3 (claim 6 of ‘314), and wherein the tumor antigen is selected from the group consisting of or Muc1 (para. 6, 8, 16, claim 4-5 of ‘314) (limitation of claims 1, 10-11). Song teaches that T cell engager-armed oncolytic virus, facilitates T cell infiltration in tumors and, through the virally-expressed T cell engager, induces bystander killing of tumor cells that are not infected by the virus, leading to an enhanced antitumor effect (see para. 7). The use of combination of bispecific antibodies (BsAb), i.e. anti-MUC1·anti-CD3 is known to enhance tumor growth inhibition by T-LAK cells against MUC1-expressing tumor cells as evident from the teaching of Yoshida (see page 97, col. 2, para. 1).
With respect to claim 12-13, Song continues to teach engager additionally comprises one or more of cytokine, a costimulatory domain, a domain that inhibits negative regulatory molecules of T-cell activation, or a combination thereof. In specific embodiments, wherein the cytokine is IL-2, and/or IL-7 (para. 49) (limitation of claims 12-13).
The combination of reference differs from claimed invention by not disclosing method further comprising administration of adoptive T- cell therapeutic composition to the subject (limitation of claim 3).
Yu cures the deficiency by disclosing a method of treating cancer by intravenous injection of viral vector encoding tumor antigen (EphA2)-scFv-CD3-scFv (see figure 1) in combination of PBMC (adoptive cells), wherein said combination significantly decrease in tumor growth compared to subject receiving only the oncolytic virus or PBMC alone (see fig. 7) (limitation of claim 2-4). Yu teaches EphA2-TEA-VVs induced significant T-cell proliferation if the cell culture medium was supplemented with 100 U/ml human IL-2. It is further disclosed that additional genetic modification of TEA-virus vector with transgenes that encode costimulatory molecules or cytokine should result in TEA-VVs that not only activate T cells but also induce robust T-cell proliferation (see Fig. 4 and 5) (limitation of claims 1-2, 4-6, 8-9). Yu teaches r EphA2-TEA-VVs activated human PBMCs and enhanced antitumor activity in preclinical models. Yu further contemplated disclosed T-cell engager arming strategy with other oncolytic viruses including oncolytic adenoviral vector (see page 109, col. 1, para. 3).
Therefore, it would have been prima facie obvious for a person of ordinary skill to combine the teachings of prior art to modify the method of Diaconu by substituting the transgene insertion with another transgene encoding a bispecific antibody comprising a single chain variable region fragment directed against a cell surface molecule and an scFv specific against a tumor antigen in the oncolytic adenoviral vector as disclosed in Song, with a reasonable expectation of success, before the effective filing date of the instant invention. Said modification amounting to combining prior art elements according to known methods to yield predictable results. It would be further obvious to one of ordinary skill in the art to modify the method of Diaconu and Song by further including intravenous injection of PBMC (adoptive cells) in combination with administration of oncolytic vector encoding tumor antigen (EphA2)-scFv-CD3-scFv (see figure 1) as suggested in Yu, with reasonable expectation of success. One of ordinary skill in the art would be motivated to do so because (i) the cDNA coding for transgene placed into a gp19k/6. 7k deleted E3 region, under the E3 promoter restricts transgene expression to tumor cells that allow replication of the virus (see page 15, lines 25-28) and (ii) bispecific antibodies (BsAb) expression of anti-MUC1·anti-CD3 is known to enhance tumor growth inhibition by cells against MUC1-expressing tumor cells (see above) and (iii) T-cell engager-armed oncolytic virus encoding secretory bispecific T-cell engagers (TEs) that bind both to human CD3 and a tumor cell surface antigen following infection activated T cells and induced T-cell killing that in presence of T cells administration had greater antitumor activity than that of unarmed oncolytic virus in presence of s T cells in a lung cancer as disclosed in Yu. One of skill in the art would have been expected to have a reasonable expectation of success because prior art successfully reported (i) insertion of a heterologous coding sequence in a deletion in the E3 region of an Ad5/3 vector as evident from the teaching of Diaconu and (ii) co administration of T-cell engager-armed oncolytic virus vector and T cell exhibited enhanced antitumor activity (see figure 7 of Yu). It should be noted that the KSR case forecloses the argument that a specific teaching, suggestion, or motivation is required to support a finding of obviousness See the recent Board decision Ex parte Smith, --USPQ2d--, slip op. at 20, (Bd. Pat. App. & Interf. June 25, 2007) (citing KSR, 82 USPQ2d at 1396) (available at http: www. uspto.gov/web/offices/dcom/bpai/prec/fd071925.pdf).
Response to arguments
To the extent that Applicants’ arguments are pertinent to the new rejections, they are addressed as follows:
Applicant disagree with the rejection arguing there is no teaching or suggestion in any of the cited references that would have provided a motivation to the skilled artisan to switch the cytokine transgene for a bispecific antibody as recited in claim 1 here, and the Examiner has not provided any reasons why a skilled artisan might have read this into the disclosures and made the change given what is contained in these references. Therefore, there would have been no reasonable expectation of success if one had done this, without motivation, to produce what is claimed. Applicants’ arguments have been fully considered, but are not found persuasive.
In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). Applicants have further engaged in selective reading of the teachings of Song to formulate the grounds for not teaching the invention. In the instant case, Hemminki et al. in describing the oncolytic adenoviral vector states “the invention is based on surprising effects, i.e. the following improvements in adoptive T-cell therapy: recruitment of transferred cells to the tumor, ii) propagation of transferred cells at the tumor, iii) enhanced reactivity of transferred cells at the tumor (Figure 20). It is further disclosed that the said combination of viral vectors and cytokines with adoptive cell therapeutics provides more effective results on wider targets than could have been assumed. Effects of the said combination of viral vectors comprising cytokine transgene with adoptive cell transfer are synergistic compared to the effects of only viral vectors comprising cytokine transgene or only adoptive cell transfers” (see page 3, lines 27-34 and page 4 , lines 1-2). A variety of engager molecule having an activation domain that recognizes a cell molecule, such as CD3, for example, on T cells and an antigen recognition domain that recognizes a tumor antigen (eg Muc1) for this purpose delivery to a subject using oncolytic viruses were well-known in the art, including (CD3 and Muc1) as evident from the teaching of Song. One of ordinary skill in the art would be motivated to use engager molecule in order to facilitates T cell infiltration in tumors as suggested in Song (see para. 7).
To the extent that Song describe oncolytic virus could encode an engager molecule having an activation domain that recognizes a cell molecule, such as CD3, for example, on T cells and an antigen recognition domain that recognizes a tumor antigen such as Muc 1 (see abstract and para. 8), the rejection is applicable to the instant case. Applicants' selective reading of Song. ignores the teachings of the primary reference of Hemminki. There is no requirement for Song to teach that which is clearly taught by Hemminki.
Applicant continue to argue that even if adenovirus alone is able to produce danger signals at the tumor, this is not sufficient to recruit T-cells to the tumor (Figure 4). For optimal enhancement of adoptive cell therapy, arming of oncolytic adenovirus with BiTE is also required (Figure 1). The claimed invention is directed to a vector which provides for counteracting tumor immunosuppression and enables recruitment of T cells to the tumor site through the claimed oncolytic adenovirus vector armed with BiTE. None of the cited references, individually or collectively, provides any guidance as to how to select a viral vector (as in the claimed invention) which will both counteract tumor immunosuppression and recruit T cells to a tumor site. Applicants’ arguments have been fully considered, but are not found persuasive.
In response it should be noted that claim require only one active step of administering via any intravenous and/or intratumorally am oncolytic adenoviral vector of the invention to treat a genus of cancer using a scFV specific only for MUC1 and cell surface maker is CD3. The wherein clause is simply reciting vector capable of performing a function (counteracting tumor immunosuppression and promoting the recruitment of T cells to the tumor cells) that is expected to be implicit to the active method step. Further, before the effective filing date of instant application, the prior art explicitly teaches that cell engager armed oncolytic virus, molecule having an activation domain that recognizes a cell molecule, such as CD3, for example, on T cells and an antigen recognition domain that recognizes a tumor antigen such as Muc1 results in infiltration of T cells in tumors and induces bystander killing of tumor cells that are not infected by the virus, leading to an enhanced antitumor effect.
Applicant continue to argue that results of Figures 12 and 13A-B of the Specification demonstrated that an unarmed adenoviral vector alone provided barely any or a weak killing effect towards tumor cells. When the unarmed vector was given with PBMCs (that included T-cells) (Figure 13A- B), the effect against tumor cells improved slightly, but with additional BiTEs, there was a significantly improved effect. In view of the above, the combination of an oncolytic adenovirus and BiTE had a clear synergistic effect with peripheral blood mononuclear cells (PBMCs), serving as effector cells, that would not have been reasonably predicted from the disclosures of Song, Yu, Hemminki, and Diaconu. Applicant in part rely on Figures 3 and 6 of Basnet 2022 demonstrate that the oncolytic adenoviral vector as recited in claim showed remarkable effects against breast cancer (T47D) and ovarian cancer, respectively. Figure 5 of Basnet 2024 shows surprising effects that intravenous administration had the same enhanced anti-tumoral effect as intratumorally administration. Concerning pancreatic cancer, Basnet 2022 teaches that breast cancer and pancreatic cancer cells are among the cancer types that possess higher MUCI1 expression than other cancer types. Applicants’ arguments have been fully considered, but are not found persuasive.
In response to unexpected superior results, it should be noted that any differences between the claimed invention and the prior art may be expected to result in some differences in properties. The issue is whether the properties differ to such an extent that the difference is really unexpected. In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). In the instant case, Hemminki’s declaration points to Figures 5 and 6 of the application showing effect of insertion of the antibody coding sequence in a deletion in the E3 region of an Ad5/3 vector. However, prior art summarized by the reference of Hemminki describes transgene insertion in a deletion in the E3 region of an Ad5/3 vector. Further, the art teaches greater antitumor activity of a combination of an armed virus vector with T cells over the combination of an unarmed virus vector with T cells similar to the effect disclosed in example 12 and 17 of the instant application (see Yu et al see page 102(1) col.2 para.2), thus the relevance of Applicants' arguments and declaration with respect to a greater antitumor activity is not apparent.
Further, the increasing the efficacy of adoptive cell therapy or T-cell therapy in a subject by administering an oncolytic adenoviral vector are described by Hemminki et al. The methodology for incorporating coding sequence within a deleted E3 region of an Ad5/3 vector was also known and considered routine in the prior art (see page 5). Therefore, the fact that coding sequence of a gene or BiTE disclosed in prior art may be incorporated in a deleted E3 region of an Ad5/3 vector of prior art to exert a greater antitumor activity is an expected result, and is the goal behind incorporation of antibody coding sequence in the oncolytic adenoviral 5 vector of Hemminki. In view of foregoing, it is apparent that Song et al suggest viral vector for the expression of genes for bipartite molecule with enhanced effect in adoptive cell therapy. It is relevant to point out that advantage of using an oncolytic adenovirus vector were known in art as evident from the teaching of Hemminki. “Expected beneficial results are evidence of obviousness of a claimed invention, just as unexpected results are evidence of unobviousness thereof.” In re Gershon, 372 F.2d 535, 538, 152 USPQ 602, 604 (CCPA 1967). Additionally, unexpected results have to be commensurate with the scope of the invention. "Whether the unexpected results are the result of unexpectedly improved results or a property not taught by the prior art, the "objective evidence of nonobviousness must be commensurate in scope with the claims which the evidence is offered to support." In other words, the showing of unexpected results must be reviewed to see if the results occur over the entire claimed range. In re Clemens, 622 F.2d 1029, 1036, 206 USPQ 289, 296 (CCPA 1980)." It is relevant to note that treatment regimen disclosed in Basnet 2022 and Basnet 2024 (both cited by applicant) is not same as one disclosed in the instant specification. For instance, Basnet (Molecular Therapy: Vol. 28 March 2023, 59-53, IDS) teaches animal were intratumorally injected 1x1010 vp of the oncolytic virus of the invention every 3 days for a total of 12 rounds or 8 rounds of injection (see page 70, col. 1, para. 4 and 5). Likewise, Basnet (Molecular Therapy: 2024, Vol. 32, 3114-3127, IDS) ) teaches a administering virus (1 x 1010 VP/tumor) or PBS intratumorally every until day 27. In the instant case, claims are not so limited. Further, the treatment regimen is also not supported by the specification. MPEP 2164.05(a) states “While a later dated publication cannot supplement an insufficient disclosure in a prior dated application to make it enabling, an applicant can offer the testimony of an expert based on the publication as evidence of the level of skill in the art at the time the application was filed. Gould v. Quigg, 822 F.2d 1074, 1077, 3 USPQ2d 1302, 1304 (Fed. Cir. 1987). There is no evidence on record the claimed unexpected benefit could be extended to the method as claimed.
Therefore, in view of the fact patterns of the instant case, and the ground of rejection outlined by the examiner, applicants’ arguments are not compelling and do not overcome the rejection of record.
Conclusion
No claims allowed.
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure. Katayose et al (Cancer Res. 1996, 56, 4205-4212) teach MUC1 x CD3 bispecific antibody could antigen-specifically enhance the cytotoxicity of LAK cells.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ANOOP K. SINGH whose telephone number is (571)272-3306. The examiner can normally be reached Monday-Friday, 8AM-5PM.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Peter Paras can be reached at (571)272-4517. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/ANOOP K SINGH/ Primary Examiner, Art Unit 1632