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 .
Election/Restrictions
Applicant’s election without traverse of Group I (Claims 1, 4-7, 9, 11-15, 17, 19, and 48-54; drawn to a viral vector) in the reply filed on December 20, 2024, is acknowledged.
Applicant further elected the following species:
An epitope from 12 to 45 nucleotide base pairs in length
Furthermore, Applicant provisionally elected the species serotype 5 in a telephone interview with the Applicant’s representative, Nicholas Upright, on February 19, 2025.
In light of the Applicant’s elected species, claims 5 and 54 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.
DETAILED ACTION
The amended claims filed on August 5, 2025, have been acknowledged. Claims 2-3, 8, 10, 16, 18, and 20-47 were cancelled. Claim 7 was amended. Claims 55-60 are new. In light of the Applicant’s elected species, claims 5 and 54 is withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Claims 1, 4, 6-7, 9, 11-15, 17, 19, 48-53, and 55-60 are pending and examined on the merits.
Priority
Applicant’s claim for the priority of a prior-filed application under 35 U.S.C. 119(a)-(d) is acknowledged. Applicant has not complied with one or more conditions for receiving the benefit of an earlier filing date as follows:
The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of 35 U.S.C. 112(a) or the first paragraph of pre-AIA 35 U.S.C. 112, except for the best mode requirement. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994).
The disclosure of the prior-filed applications, Application No. GB19149848, filed October 16, 2019, and Application No. GB20094207, filed June 19, 2020, fail to provide adequate support or enablement in the manner provided by 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph for one or more claims of this application. These foreign priority applications do not provide information related to SEQ ID NOs: 13-15, 18-19, and 33. However, Application No. PCT/GB2020/052620, filed on October 16, 2020, did provide the above information.
Therefore, claims 1, 4, 6-7, 9, 11-15, 17, 19, 50-53, and 55-60 receive foreign priority from foreign priority application GB19149848, filed October 16, 2019, while claims 48-49 receive foreign priority from application No. PCT/GB2020/052620, filed on October 16, 2020.
Information Disclosure Statement
The information disclosure statement (IDS) filed on August 11, 2025, has been considered.
Withdrawn Claim Rejections - 35 USC § 112
The prior rejection of claims 51-52 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention is withdrawn in light of Applicant’s amendments to claims 51-52 to remove the “low” language.
New Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1, 4, 6-7, 9, 11-15, 17, 19, 48-53, and 55-58 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claim 1 recites the following claim language, “A viral vector comprising a nucleotide sequence encoding a single cancer specific CD8+ T cell epitope, …wherein the viral vector induces an inflating memory CD8+ T cell response when administered to a human subject, wherein the inflating memory CD8+ T cell response is characterized by the production of CD8+/CX3CR1+/KLRG-1+ T cells that have sustained expression of Tbx21 and/or E2f2, and wherein (i) the CD8+/CX3CR1+/KLRG-1+ T cells form 2 percent to 20 percent of total circulating CD8+ T cells in the subject, or (ii) the CD8+/CX3CR1+/KLRG-1+ T cells maintain a memory effector phenotype for at least 60 days post exposure to the viral vector.”
Claim 58 recites following claim language “A viral vector comprising a nucleotide sequence encoding a single cancer specific CD8+ T cell epitope, … wherein the viral vector induces an inflating memory CD8+ T cell response when administered to a subject, wherein the inflating memory CD8+ T cell response is characterized by the production of CD8+/CX3CR1+/KLRG-1+ T cells, and wherein … (ii) the CD8+/CX3CR1+/KLRG-1+ T cells maintain a memory effector phenotype for up to 60 days post exposure to the viral vector”.
Regarding the viral vector of claim 1 and claim 58, the broadest reasonable interpretation is that any single cancer specific CD8+ T cell epitope will generate an inflating memory CD8+ T cell response characterized by the production of CD8+/CX3CR1+/KLRG-1+ T cells that have sustained expression of Tbx21 and/or E2f2, and wherein (i) the CD8+/CX3CR1+/KLRG-1+ T cells form 2 percent to 20 percent of total circulating CD8+ T cells in the subject, and the CD8+/CX3CR1+/KLRG-1+ T cells maintain a memory effector phenotype for at least 60 days post exposure to the viral vector (claim 1) or just the CD8+/CX3CR1+/KLRG-1+ T cells maintain a memory effector phenotype for at least 60 days post exposure to the viral vector (claim 58). The specification does not disclose a single cancer specific CD8+ T cell epitope capable of generating the required response nor is it clear that any CD8+ T cell epitope would be capable of generating the required inflating memory CD8+ T cell response.
Under the written description guidelines (see MPEP 2163) the Examiner is directed to determine whether one skilled in the art would recognize that the Applicant was in possession of the claimed invention as a whole at the time of filing. The following considerations are critical to this determination.
To satisfy the written description requirement, a patent specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention. See, e.g., Moba, B.V. v. Diamond Automation, Inc., 325 F.3d 1306, 1319, 66 USPQ2d 1429, 1438 (Fed. Cir. 2003); Vas-Cath, Inc. v. Mahurkar, 935 F.2d at 1563, 19 USPQ2d at 1116. An original claim may lack written description support when (1) the claim defines the invention in functional language specifying a desired result but the disclosure fails to sufficiently identify how the function is performed or the result is achieved or (2) a broad genus claim is presented but the disclosure only describes a narrow species with no evidence that the genus is contemplated. See Ariad Pharms., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1349-50 (Fed. Cir. 2010) (en banc). The written description requirement is not necessarily met when the claim language appears in ipsis verbis in the specification. "Even if a claim is supported by the specification, the language of the specification, to the extent possible, must describe the claimed invention so that one skilled in the art can recognize what is claimed. The appearance of mere indistinct words in a specification or a claim, even an original claim, does not necessarily satisfy that requirement." Enzo Biochem, Inc. v. Gen-Probe, Inc., 323 F.3d 956, 968, 63 USPQ2d 1609, 1616 (Fed. Cir. 2002).
Accordingly, to satisfy the written description requirement, the specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention. Vas-Cath, Inc. v. Mahurkar, 935 F.2d 1555, 1562-63, 19 USPQ2d 1111 (Fed. Cir. 1991). See also MPEP 2163.
Actual Reduction to Practice
In regard to claims 1 and 58 encompassing a genus of viral vectors comprising a nucleotide sequence encoding a single cancer specific CD8+ T cell epitope, …wherein the viral vector induces an inflating memory CD8+ T cell response when administered to a human subject, wherein the inflating memory CD8+ T cell response is characterized by the production of CD8+/CX3CR1+/KLRG-1+ T cells that have sustained expression of Tbx21 and/or E2f2, and wherein (i) the CD8+/CX3CR1+/KLRG-1+ T cells form 2 percent to 20 percent of total circulating CD8+ T cells in the subject, and the CD8+/CX3CR1+/KLRG-1+ T cells maintain a memory effector phenotype for at least 60 days post exposure to the viral vector (claim 1) or just the CD8+/CX3CR1+/KLRG-1+ T cells maintain a memory effector phenotype for at least 60 days post exposure to the viral vector (claim 58), the specification provides no examples of a single epitope capable of generating the required responses when administered to a subject.
Accordingly, Applicant did not demonstrate a reduction to practice of a viral vector comprising a nucleotide sequence encoding a single cancer specific CD8+ T cell epitope capable of generating the required inflating memory T cell response, nor did Applicant adequately set forth in terms of distinguishing identifying characteristics as evidenced by other descriptions of the invention that are sufficiently detailed to show that Applicant was in possession of the claimed genus viral vectors comprising a nucleotide sequence encoding a single cancer specific CD8+ T cell epitope capable of generating the required inflating memory T cell response
Disclosure of structure
The Applicant has provided no viral vector comprising a nucleotide sequence encoding a single cancer specific CD8+ T cell epitope capable of generating the required inflating memory T cell responses.
Regarding the maintenance of CD8+/CX3CR1+/KLRG-1+ T cells for 60 days post exposure, Applicant has provided no examples of an antigen capable of maintaining these cell types. Applicant does disclose in Example 7 and Figure 7 that CD8+/CX3CR!+ cells are maintained for approximately 6 months after the viral vector encoding an AH1 epitope was administered in mice that cleared the tumors. However, Applicant does not identify whether these CD8+/CX3CR1+ cells are KLRG-1+ cells. Although Applicant does disclose in Example 3 and Figure 3 that AH1 encoding viral vectors led to CD8+/CX3CR1+/KLRG-1+ T cells (at least 20% of CD8+ cells are CX3CR1+ (79.3% of CD8+ cells are +) and KLRG1+ (41.1% of CD8+ cells are +) in the tumor, these are identified as having an exhausted phenotype and unlikely to remain long term. Regarding the spleen, it is not clear that the spleen has CD8+/CX3CR1+/KLRG-1+nor is it clear that if it did, that any CD8+/CX3CR1+/KLRG-1+ T cells would still be circulating at the 6 month mark. Therefore, the Applicant has provided no examples of an epitope capable of maintaining a population of CD8+/CX3CR1+/KLRG-1+ T cells for 60 days post exposure.
Regarding the 2-20% of circulating T cells and sustained expression of Tbx21, Applicant has provided examples of individual epitopes, NY-ESO-1157-165 and AH1, respectively, that are capable of generating these phenotypes but no single epitope that can generate the required inflating memory T cell responses.
Applicant discloses in Example 8 and Figure 8 that they immunized HHD mice with AdHu5-NY-ESO-1(157-165) and saw that HHD mice immunized with AdHu5- NY-ESO-1157-165 minigene construct develop a long-lived circulating population of NY-ESO-1157-165 Tet+ CD8 T cells with an inflating memory phenotype. As shown in Figure 8 of the instant specification, following immunization, ~100% were CX3CR1+ and ~65% were KLRG-1+ at day 40 (Figures 8C and D). As such, there were at least 65% of cells that were CD8+/CX3CR1+/KLRG-1+ at day 40. As shown in Figure 8A, these cell phenotypes at day 40 were only representative of ~12% of CD8+ T cells. Therefore, ~7% of CD8+ cells were CD8+/CX3CR1+/KLRG-1+ at day 40.
Applicant discloses in Example 15 and Figure 15 that the AH1 minigene construct led to increased Tbx21 (also known as Tbet) expression 23 days after tumor implantation in the tumor and in the spleen. Applicant did not examine Tbx21 expression with any other construct.
Sufficient relevant identifying characteristics
The breadth of the claims encompass a genus of viral vectors comprising a nucleotide sequence encoding a single cancer specific CD8+ T cell epitope capable of generating the required inflating memory T cell responses, yet the present specification provides no guidance nor description which epitopes are capable of generating the required inflating memory T cell responses, therefore the skilled artisan would not know what rational approach to take to make the genus of viral vectors comprising a nucleotide sequence encoding a single cancer specific CD8+ T cell epitope capable of generating the required inflating memory T cell responses. Therefore, it is incumbent on the applicant to provide this nexus between structure and function, in order to be given credit for possession of the claimed genus of vectors.
An applicant may show that an invention is complete by disclosure of sufficiently detailed, relevant identifying characteristics which provide evidence that applicant was in possession of the claimed invention, i.e., complete or partial structure, other physical and/or chemical properties, functional characteristics when coupled with a known or disclosed correlation between function and structure, or some combination of such characteristics. Enzo Biochem, 323 F.3d at 964, 63 USPQ2d at 1613.
STATE OF THE ART & QUANTITY OF EXPERIMENTATION
The method of making the claimed invention is not well established. Although the making of the claimed viral vectors was known in the state of the art, one of skill in the art would neither expect nor predict the appropriate epitopes to use that would generate the required inflating memory T cell responses. The following describes the state of the art with respect to viral vectors encoding epitopes to generate an inflating memory T cell response. The prior art teaches adenoviruses, MCMV, and vaccinia viruses encoding single CD8+ T cell epitopes capable of generating CD8+ T cell responses, as identified by Bolinger et al. (Cell Reports 13: 1578-1588. 2015; referenced in IDS), Klyushnenkova et al. (J Immunother 35: 390-399. 2012), and Palmowski et al. (J Immunol 168: 4391-4398. 2002).
Bollinger teaches that they examined the inflationary memory T cell response ifrom adenoviral vectors encoding two different βgal epitopes, βgal96 and βgal497. Both epitopes were able to elicit a CD8 T cell response (Figure 2) but with distinct differences in sustained CD8 T cell responses and gene expression (Figures 2-3). Therefore, even epitopes from the same gene can have different CD8 T cell responses.
Klyushnenkova teaches a method of inducing an inflating memory CD8+ T cell response comprising administering a recombinant mCMV viral vector encoding a CD8 T cell epitope (PSA65-73; a cancer specific CD8+ T cell epitope) to a subject before challenging it with a tumor (i.e. prophylactic administration to minimize development of cancer). Their results show that immunization with mCMV based vectors encoding a single PSA-specific CD8 T-cell epitope (PSA65–73) induced PSA-specific CD8 T-cell responses, which increased in time after immunization (termed “memory inflation”) and reduced tumor growth (page 391, column 1, paragraph 2 and column 2, paragraph 2 and Figure 4). Klyushnenkova does not identify whether their viral vector causes an inflating memory T cell response as required by claims 1 and 58.
Palmowski teaches administering a vaccinia viral vector encoding the NY-ESO-1157-165- cancer epitope to a A2/Kb transgenic mouse. Their results show that immunization with vaccinia based vectors encoding a single NY-ESO-1157-165- cancer epitope induced an antigen-specific cytotoxic T lymphocyte [CTL] response including inducing CD8 T cell levels (page 4393, column 2, paragraph 3 and Figure 3). Palmowski does not identify whether their viral vector causes an inflating memory T cell response as required by claims 1 and 58.
Therefore, although the prior art provides examples of single cancer specific CD8+ T cell epitopes capable of generating a CD8+ T cell response, they do not teach that they generate the required inflating memory T cell responses as claimed. Furthermore, Bollinger identifies that there are differences in the CD8 T cell response between CD8+ T cell epitopes.
Applicant has claimed a genus of viral vectors comprising a nucleotide sequence encoding a single cancer specific CD8+ T cell epitope capable of generating the required inflating memory T cell responses, yet the specification has not disclosed viral vectors capable of generating the claimed inflating memory T cell response, has not set forth in terms of distinguishing identifying characteristics as evidenced by other descriptions of the invention that are sufficiently detailed to show that Applicant was in possession of the claimed genus of viral vectors. Furthermore, the state of the art indicated a limited number of potential epitopes that are capable of generating a CD8+ T cell response, but do not teach that they generate the required inflating memory T cell responses as claimed and shows that there are differences in the CD8 T cell response between CD8+ T cell epitopes. However, the claims are much broader to the epitopes identified in the specification and prior art and would require undue experimentation to identify vectors that fall within the limitations of claims 1 and 58, and one of skill in the art would neither expect nor predict which vectors encoding cancer specific CD8 T cell epitopes would generate a inflating memory T cell response as claimed.
CONCLUSION
Therefore, the Examiner concludes that there is insufficient written description of the instantly claimed genus of viral vectors comprising a nucleotide sequence encoding a single cancer specific CD8+ T cell epitope capable of generating the required inflating memory T cell responses. Specifically, there is limited description of the structure-function relationship between the claimed genus of vectors and their ability to produce the required inflating memory T cell responses, and the Examiner further concludes a skilled artisan would find the specification inadequately describes the claimed genus of vectors.
Withdrawn Claim Rejections - 35 USC § 103
The prior rejections of claims 1, 4, 6-7, 9, 11-12, 14-15, 19, 50, and 52-53 under 35 U.S.C. 103 as being unpatentable over Palmowski et al. (J Immunol 168: 4391-4398. 2002) and further in view of Weiser et al. (Journal of Immunotherapy 24: 151-161. 2001), and Geiben-Lynn et al. (Clinical and Vaccine Immunology: 691–696. 2008) is withdrawn in light of Applicant’s amendments to claim 1 to recite new functional limitations for the inflating memory CD8+ T cell response.
The prior rejections of claims 1 and 17 under 35 U.S.C. 103 as being unpatentable over Palmowski et al. (J Immunol 168: 4391-4398. 2002), Weiser et al. (Journal of Immunotherapy 24: 151-161. 2001), and Geiben-Lynn et al. (Clinical and Vaccine Immunology: 691–696. 2008), as applied to claim 1 above, and further in view of Klyushnenkova et al. (J Immunother 35: 390-399. 2012) is withdrawn in light of Applicant’s amendments to claim 1 to recite new functional limitations for the inflating memory CD8+ T cell response.
The prior rejections of claims 1 and 48 under 35 U.S.C. 103 as being unpatentable over Palmowski et al. (J Immunol 168: 4391-4398. 2002), Weiser et al. (Journal of Immunotherapy 24: 151-161. 2001), Geiben-Lynn et al. (Clinical and Vaccine Immunology: 691–696. 2008), as applied to claim 1 above, and further in view of United States Patent No. 9981033 (Mebatsion), as evidenced by Genbank (Human adenovirus 5, complete genome) is withdrawn in light of Applicant’s amendments to claim 1 to recite new functional limitations for the inflating memory CD8+ T cell response.
The prior rejections of claims 1 and 48-49 under 35 U.S.C. 103 as being unpatentable over Palmowski et al. (J Immunol 168: 4391-4398. 2002), Weiser et al. (Journal of Immunotherapy 24: 151-161. 2001), Geiben-Lynn et al. (Clinical and Vaccine Immunology: 691–696. 2008), and United States Patent No. 9981033 (Mebatsion), as applied to claims 1 and 48 above, and further in view of World Intellectual Property Organization Patent Application No. 2019034887 (Dorrell) is withdrawn in light of Applicant’s amendments to claim 1 to recite new functional limitations for the inflating memory CD8+ T cell response.
The prior rejections of claims 1, 4, 6-7, 9, 11-12, 14-15, 19, and 50-51 under 35 U.S.C. 103 as being unpatentable over Kershaw et al. (Cancer Res. 61: 7920–7924. 2001) and further in view of Geiben-Lynn et al. (Clinical and Vaccine Immunology: 691–696. 2008) is withdrawn in light of Applicant’s amendments to claim 1 to recite new functional limitations for the inflating memory CD8+ T cell response.
The prior rejections of claims 1 and 13 under 35 U.S.C. 103 as being unpatentable over Kershaw et al. (Cancer Res. 61: 7920–7924. 2001) and further in view of Geiben-Lynn et al. (Clinical and Vaccine Immunology: 691–696. 2008), as applied to claim 1 above and further in view of Sorensen et al. (Eur. J. Immunol. 39: 2725–2736. 2009) is withdrawn in light of Applicant’s amendments to claim 1 to recite new functional limitations for the inflating memory CD8+ T cell response.
The prior rejections of claims 1 and 48 under 35 U.S.C. 103 as being unpatentable over Kershaw et al. (Cancer Res. 61: 7920–7924. 2001) and Geiben-Lynn et al. (Clinical and Vaccine Immunology: 691–696. 2008), as applied to claim 1 above, and further in view of United States Patent No. 9981033 (Mebatsion), as evidenced by Genbank (Human adenovirus 5, complete genome) is withdrawn in light of Applicant’s amendments to claim 1 to recite new functional limitations for the inflating memory CD8+ T cell response.
The prior rejections of claims 1 and 48-49 under 35 U.S.C. 103 as being unpatentable over Kershaw et al. (Cancer Res. 61: 7920–7924. 2001), Geiben-Lynn et al. (Clinical and Vaccine Immunology: 691–696. 2008), and United States Patent No. 9981033 (Mebatsion), as applied to claims 1 and 48 above, and further in view of World Intellectual Property Organization Patent Application No. 2019034887 (Dorrell) is withdrawn in light of Applicant’s amendments to claim 1 to recite new functional limitations for the inflating memory CD8+ T cell response.
New 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.
Claims 58 and 60 are rejected under 35 U.S.C. 103 as being unpatentable over Palmowski et al. (J Immunol 168: 4391-4398. 2002) and further in view of Weiser et al. (Journal of Immunotherapy 24: 151-161. 2001), Geiben-Lynn et al. (Clinical and Vaccine Immunology: 691–696. 2008), and Le Gallo et al. (J Gene Med 10: 628–636. 2008).
Regarding claim 58, Palmowski teaches administering a vaccinia viral vector encoding the NY-ESO-1157-165- cancer epitope to a A2/Kb transgenic mouse. Their results show that immunization with vaccinia based vectors encoding a single NY-ESO-1157-165- cancer epitope induced an antigen-specific cytotoxic T lymphocyte [CTL] response including inducing CD8 T cell levels (page 4393, column 2, paragraph 3 and Figure 3).
Palmowski does not teach wherein the viral vector is an adenovirus.
Weiser teaches that lung cancer cells (H-1355) were transduced with an adenovirus expressing full length NY-ESO-1. Although high levels of NY-ESO-1 were expressed following transduction, cancer cell death did not occur likely due to deficient antigen processing which is commonly observed in lung cancer (page 156, column 1, paragraph 1 and Table 2).
Geiben-Lynn teaches that mice vaccinated with vaccinia viruses (replication competent or replication incompetent) led to early animal death (replication competent) or short term expression (~48 hours for immunocompetent and immunocompromised mice; replication incompetent) while the adenovirus vaccine (recombinant adenovirus 5 with E1 and E3 deleted maintained for ~10 days in immunocompetent mice and at least 100 days in immunocompromised mice (page 691, column 2, paragraph 3 and page 692, column 2, paragraph and Figures 1-3).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have substituted the vaccinia viral vector backbone of Palmowski with the adenoviral vector backbone of Weiser and Geiben-Lynn to arrive at the instantly claimed invention. One of ordinary skill in the art would have a reason to substitute with a reasonable expectation of success because Geiben-Lynn teaches that mice vaccinated with vaccinia viruses (replication competent or replication incompetent) led to early animal death (replication competent) or short term expression (~48 hours for immunocompetent and immunocompromised mice; replication incompetent) while the adenovirus vaccine maintained for ~10 days in immunocompetent mice and at least 100 days in immunocompromised mice. As such, the adenovirus backbone would have been an obvious substitute for expressing the epitope. Because the prior art teaches all of the elements of the claimed invention, there is a reasonable expectation of success.
The combined teachings of Palmowski, Weiser, and Geiben-Lynn do not teach wherein the promoter is a CMV promoter.
However, Le Gallo teaches that they transfected dendritic cells with a plasmid encoding the full length NY-ESO-1 cDNA under the control of a CMV promoter and found that the CMV promoter was able to drive expression of NY-ESO-1 in the dendritic cell and lead to presentation of the class I restricted epitope NY-ESO-1157-165 (abstract and page 629, column 2, paragraph 2-page 635, column 1, paragraph 3). CMV is known to possess a TATA box to start transcription of the gene of interest.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have used a CMV promoter. One of ordinary skill in the art would have a reason to use a CMV promoter with a reasonable expectation of success because Le Gallo has successfully reduced to practice that CMV reporters can be used to express the NY-ESO-1 full length gene which encompasses the NY-ESO-1-157-165 immunodominant epitope. Furthermore, CMV promoters are known to be constitutively active ensuring continued expression of the epitope over time and have been used extensively within the field. Because the prior art teaches all of the elements of the claimed invention, there is a reasonable expectation of success.
Regarding the limitation wherein the viral vector induces an inflating memory CD8+ T cell response when administered to a subject, as stated supra, Palmowski teaches the vector encodes NY-ESO-1157-165, Geiben-Lynn teaches that the adenoviral vector is a recombinant adenovirus 5 with E1 and E3 deleted, and Palmowski teaches that the vaccination can occur in HHD mice. Examples 8-9 of the instant specification discloses that they immunized HHD mice with AdHu5-NY-ESO-1(157-165) (an adenovirus 5 with E1 and E3 deleted) and saw that HHD mice immunized with AdHu5- NY-ESO-1157-165 minigene construct develop a long-lived circulating population of NY-ESO-1157-165 Tet+ CD8 T cells with an inflating memory phenotype. As shown in Figure 8 of the instant specification, following immunization, ~100% were CX3CR1+ and ~65% were KLRG-1+ at day 40 (Figures 8C and D). As such, there were at least 65% of cells that were CD8+/CX3CR1+/KLRG-1+ at day 40. As shown in Figure 8A, these cell phenotypes at day 40 were only representative of ~12% of CD8+ T cells. As such, ~7% of CD8+ cells were CD8+/CX3CR1+/KLRG-1+ at day 40. As the combined vector of Palmowski, Weiser, and Geiben-Lynn is the same as the example of the instant specification, it naturally flows that their combined vector would also have the same properties. It is noted that the MPEP states that,”.. in apparatus, article, and composition claims, intended use must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art.” In re Casey, 152 USPQ 235 (CCPA 1967); In re Otto , 136 USPQ 458, 459 (CCPA 1963)(MPEP 2111.02). Since the prior art structure is capable of performing the intended use, then it meets the claim. As the combined vector of Palmowski, Weiser, and Geiben-Lynn is the same as the example of the instant specification, it naturally flows that their vector would also have the same property.
Regarding claim 60, the instant specification discloses that by using a vector of the present invention, which encodes a single epitope of interest, the antigen processing requirements are bypassed thereby resulting in an inflating memory response (page 12, lines 1-16). As the composition of the Palmowski, Weiser, and Geiben-Lynn is the same as the vector of examples 8-9 of the instant application, it naturally flows that the NY-ESO-1157-165 epitope of the combined teachings would also not be processed by APC cells of the subject, thus bypassing normal antigen processing requirements for presentation on an MHC molecule.
Response to Arguments
Applicant's arguments filed August 5, 2025, are acknowledged.
Applicant argues that new claim 58 recites the limitations of previous claims 1 and 13 and claim 13 was not rejected over the teachings of Palmowski, Weiser, and Geiben-Lynn. Therefore, claim 58 is non-obvious over Palmowski, Weiser, and Geiben-Lynn (page 10, paragraphs 3-4).
Applicant's arguments have been fully considered but they are not persuasive.
Claim 58 has been rejected over the combined teachings of Palmowski, Weiser, Geiben-Lynn, and Le Gallo which teach all of the limitations of claim 58. Therefore, Applicant’s arguments are considered moot.
Applicant argues that new claim 60 recites limitations that are not taught by the combined teachings of Palmowski, Weiser, and Geiben-Lynn. Therefore, claim 60 is non-obvious over Palmowski, Weiser, and Geiben-Lynn (page 11, paragraphs 3-4).
Applicant's arguments have been fully considered but they are not persuasive.
Although Applicant argues that “wherein the viral vector is capable of inducing the inflating memory CD8+ T cell response to the single cancer specific CD8+ T cell epitope when administered to a subject that has not previously been administered a polypeptide comprising the single cancer specific CD8+ T cell epitope or nucleic acid comprising a sequence encoding the single cancer specific CD8+ T cell epitope” is not taught by the combined teachings of Palmowski, Weiser, and Geiben-Lynn, Applicant does not provide any arguments as to why they believe this limitation is not taught.
As stated supra, Palmowski teaches administering a vaccinia viral vector encoding the NY-ESO-1157-165¬ cancer epitope to a A2/Kb transgenic mouse. Their results show that immunization with vaccinia based vectors encoding a single NY-ESO-1157-165¬ cancer epitope induced an antigen-specific cytotoxic T lymphocyte [CTL] response including inducing CD8 T cell levels (page 4393, column 2, paragraph 3 and Figure 3). Palmowski teaches the vector encodes NY-ESO-1157-165, Geiben-Lynn teaches that the adenoviral vector is a recombinant adenovirus 5 with E1 and E3 deleted, and Palmowski teaches that the vaccination can occur in HHD mice. Examples 8-9 of the instant specification discloses that they immunized HHD mice with AdHu5-NY-ESO-1(157-165) (an adenovirus 5 with E1 and E3 deleted) and saw that HHD mice immunized with AdHu5- NY-ESO-1157-165 minigene construct develop a long-lived circulating population of NY-ESO-1157-165 Tet+ CD8 T cells with an inflating memory phenotype. As shown in Figure 8 of the instant specification, following immunization, ~100% were CX3CR1+ and ~65% were KLRG-1+ at day 40 (Figures 8C and D). As such, there were at least 65% of cells that were CD8+/CX3CR1+/KLRG-1+ at day 40. As shown in Figure 8A, these cell phenotypes at day 40 were only representative of ~12% of CD8+ T cells. As such, ~7% of CD8+ cells were CD8+/CX3CR1+/KLRG-1+ at day 40. As the combined vector of Palmowski, Weiser, and Geiben-Lynn is the same as the example of the instant specification, it naturally flows that their combined vector would also have the same properties. It is noted that the MPEP states that,”.. in apparatus, article, and composition claims, intended use must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art.” In re Casey, 152 USPQ 235 (CCPA 1967); In re Otto , 136 USPQ 458, 459 (CCPA 1963)(MPEP 2111.02). Since the prior art structure is capable of performing the intended use, then it meets the claim. As the combined vector of Palmowski, Weiser, and Geiben-Lynn is the same as the example of the instant specification, it naturally flows that their vector would also have the same property.
Therefore, the viral vector of the combined teachings of Palmowski, Weiser, Geiben-Lynn, and Le Gallo would fall within the limitations of claim 60.
As the Applicant has not cited any reasoning as to why they believe the combined teachings do not teach the bolded limitation, their arguments are considered unpersuasive.
Claims 59-60 are rejected under 35 U.S.C. 103 as being unpatentable over Kershaw et al. (Cancer Res. 61: 7920–7924. 2001), Sugiyarto et al. (BioRxiv: Protective low avidity anti-tumour CD8+ T cells are selectively attenuated by regulatory T cells. 1-37. 2018), Palmowski et al. (J Immunol 168: 4391-4398. 2002), Colston et al. (J Immunol 196: 3354–3363. 2016; referenced in IDS), Klyushnenkova et al. (J Immunother 35: 390-399. 2012), and Geiben-Lynn et al. (Clinical and Vaccine Immunology: 691–696. 2008).
Regarding claim 59, Kershaw teaches a vaccinia virus encoding the gp70 immunodominant epitope (SPSYVYHQF; also known as AH1) to immunize mice against a CT26 tumor challenge (page 2, paragraph 5 and abstract).
Kershaw does not teach wherein the vector encoding the gp70 immunodominant epitope is combined with another vector encoding a different cancer specific CD8+ T cell epitope.
Sugiyarto teaches that the CT26-immune mice developed memory CTL responses and were able to reject a second challenge with CT26 as well as tumour lines of different histological origin following recovery of Tregs to normal levels. Anti-tumour responses in these mice are focused on two epitopes derived from gp90; AH1 (SPSYVYHQF) and GSW11 (GGPESFYCASW). Sugiyato teaches that anti-GSW11 CD8+ T cells deliver the most potent anti-tumour response characterised by their ability to reject tumours expressing very low levels of antigen (lines 80-89).
Palmowksi teaches a polyvirus boosting protocol for treating melanoma wherein a mixture of 108 mel3-SFV, 106 NY-ESO-1 vaccinia, and 106 tyrosinase vaccinia in a total volume of 300. Palmowski found that the combined vaccination produced higher levels of CD8+ cells specific to NY-ESO-1 and Tyrosinase than when they were used separately (page 4392, column 2, paragraph 1 and Figure 6). Palmowski is using the full length protein of NY-ESO-1 and tyrosinase in the polyvirus composition.
Colston teaches that they tested whether a single host could accommodate multiple inflationary responses from minigene constructs and observed that inflation occurred using this combined minigene vaccination when the vectors were given at the same site. These data indicate that coinduction of memory inflation is possible using the minigene approach, and that competition for presentation or for T cell expansion does not impact on the pathway of memory development (page 3359, column 1, paragraph 2-column 2, paragraph 1 and Figure 5).
Klyushnenkova teaches that animals receiving mCMV/PSA65–73 (single epitope) demonstrated a substantial level of PSA-specific CD8 T cells, whereas animals receiving mCMV/PSA Full Length did not generate an increased CTL [cytotoxic T lymphocyte] response to PSA (page 397, column 2, paragraph 2).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have combined the vaccinia virus encoding the AH1 epitope with a second vaccinia virus encoding the GSW11 epitope to arrive at the instantly claimed invention. One of ordinary skill in the art would have a reason to combine with a reasonable expectation of success because Palmowski teaches that a multi vaccinia virus boosting protocol can be used to treat a cancer wherein a mixture of vaccinia viruses encoding polyepitopes (NY-ESO-1 and tyrosinase) can be delivered to a mouse to improve their CD8 T cell response compared to when the polyepitope viruses are delivered alone. Sugiyarto teaches that anti-tumour responses against CT26 tumors are focused on two epitopes derived from gp90; AH1 (SPSYVYHQF) and GSW11 (GGPESFYCASW) and that anti-GSW11 CD8+ T cells deliver the most potent anti-tumour response characterised by their ability to reject tumours expressing very low levels of antigen. Colston teaches that they tested whether a single host could accommodate multiple inflationary responses from minigene constructs and observed that inflation occurred using this combined minigene vaccination when the vectors were given at the same site. Furthermore, Klyushnenkova teaches that animals receiving mCMV/PSA65–73 (single epitope) demonstrated a substantial level of PSA-specific CD8 T cells, whereas animals receiving mCMV/PSA Full Length did not generate an increased CTL [cytotoxic T lymphocyte] response to PSA. As such, it would have been obvious to combine vaccinia viruses encoding AH1 or GSW11 single epitopes into a single composition for administering to a subject with a CT26 tumor to generate a better CD8 and anti-tumor response. Because the prior art teaches all of the elements of the claimed invention, there is a reasonable expectation of success.
The combined teachings of Kershaw, Sugiyarto, Palmowski, Colston, and Klyushnenkova do not teach wherein the viral vectors are adenoviruses.
Geiben-Lynn teaches that mice vaccinated with vaccinia viruses (replication competent or replication incompetent) led to early animal death (replication competent) or short term expression (~48 hours for immunocompetent and immunocompromised mice; replication incompetent) while the adenovirus vaccine (recombinant adenovirus 5 with E1 and E3 deleted maintained for ~10 days in immunocompetent mice and at least 100 days in immunocompromised mice (page 691, column 2, paragraph 3 and page 692, column 2, paragraph and Figures 1-3).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have substituted the vaccinia viral vector backbone of vectors of the combined teachings of Kershaw, Sugiyarto, Palmowski, Colston, and Klyushnenkova with the adenoviral vector backbone of Geiben-Lynn to arrive at the instantly claimed invention. One of ordinary skill in the art would have a reason to substitute with a reasonable expectation of success because Geiben-Lynn teaches that mice vaccinated with vaccinia viruses (replication competent or replication incompetent) led to early animal death (replication competent) or short term expression (~48 hours for immunocompetent and immunocompromised mice; replication incompetent) while the adenovirus vaccine maintained for ~10 days in immunocompetent mice and at least 100 days in immunocompromised mice. As such, the adenovirus backbone would have been an obvious substitute for expressing the epitopes. Because the prior art teaches all of the elements of the claimed invention, there is a reasonable expectation of success.
Regarding the limitation wherein the viral vector induces an inflating memory CD8+ T cell response when administered to a subject, as stated supra, Kershaw teaches the vector encodes the AH1 epitope and Geiben-Lynn teaches that the adenoviral vector is a recombinant adenovirus 5 with E1 and E3 deleted. Kershaw teaches the vector encodes AH1 and Geiben-Lynn teaches that the adenoviral vector is a recombinant adenovirus 5 with E1 and E3 deleted. Example 3 and Figure 3 shows that at least 20% of tumor CD8 cells express Cx3CR1 and KLRG1. Example 15 and corresponding Figure 15 of the instant specification disclose that AH1 expressing vectors cause sustained Tbet (or Tbx21) expression when the Ah1 minigene is administered. Therefore, combined administration of AH1 adenoviral vectors and GSW11 adenoviral vectors would also cause the same response.
As the combined vector of Kershaw, Sugiyarto, Palmowski, Colston, Klyushnenkova, and Geiben-Lynn is the same as the example of the instant specification, it naturally flows that their vector method would also have the same property.
Regarding claim 60, the instant specification discloses that by using a vector of the present invention, which encodes a single epitope of interest, the antigen processing requirements are bypassed thereby resulting in an inflating memory response (page 12, lines 1-16). As the composition of the Kershaw, Sugiyarto, Palmowski, Colston, Klyushnenkova, and Geiben-Lynn comprises a vector that is the same as the vector of examples 1-7 and 15 of the instant application, it naturally flows that the it naturally flows that the AH1 epitope of the combined teachings would also not be processed by APC cells of the subject, thus bypassing normal antigen processing requirements for presentation on an MHC molecule.
Response to Arguments
Applicant's arguments filed August 5, 2025, are acknowledged.
Applicant argues that new claim 59 recites the limitations of previous claims 1 and 17 and claim 17 was not rejected over the teachings of Kershaw and Geiben-Lynn. Therefore, claim 59 is non-obvious over Kershaw and Geiben-Lynn (page 14, paragraphs 3-4).
Applicant's arguments have been fully considered but they are not persuasive.
Claim 59 has been rejected over the combined teachings of Kershaw, Sugiyarto, Palmowski, Colston, Klyushnenkova, and Geiben-Lynn which teach all of the limitations of claim 59. Therefore, Applicant’s arguments are considered moot.
Applicant argues that new claim 60 recites limitations that are not taught by the combined teachings of Kershaw and Geiben-Lynn. Therefore, claim 60 is non-obvious over Palmowski, Weiser, and Geiben-Lynn (page 11, paragraphs 3-4).
Applicant's arguments have been fully considered but they are not persuasive.
Although Applicant argues that “wherein the single cancer specific CD8+ T cell epitope encoded by the adenoviral vector is configured to circumvent the normal antigen processing requirements for presentation on an MHC molecule” is not taught by the combined teachings of Kershaw and Geiben-Lynn nor wherein there would be a reasonable expectation of success and no motivation to make the modification, Applicant does not provide any arguments as to why they believe this limitation is not taught, why there is no reasonable expectation of success, and why there would be no motivation.
As stated supra, the instant specification discloses that by using a vector of the present invention, which encodes a single epitope of interest, the antigen processing requirements are bypassed thereby resulting in an inflating memory response (page 12, lines 1-16). As the composition of the Kershaw, Sugiyarto, Palmowski, Colston, Klyushnenkova, and Geiben-Lynn comprises a vector that is the same as the vector of examples 1-7 and 15 of the instant application, it naturally flows that the it naturally flows that the AH1 epitope of the combined teachings would also not be processed by APC cells of the subject, thus bypassing normal antigen processing requirements for presentation on an MHC molecule.
Therefore, the viral vector of the combined teachings of Kershaw, Sugiyarto, Palmowski, Colston, Klyushnenkova, and Geiben-Lynn would fall within the limitations of claim 60.
As the Applicant has not cited any reasoning as to why they believe the combined teachings do not teach the claimed limitations, why there is no reasonable expectation of success, and why there would be no motivation, their arguments are considered unpersuasive.
Withdrawn Double Patenting
The prior rejection of claims 1, 4, 6-7, 11-15, 19, and 48-53 on the ground of nonstatutory double patenting as being unpatentable over claims 1, 4-6, 8-20, 23, and 28 of copending Application No. 18/418,855 (reference application) is withdrawn in light of Applicant’s amendments to claim 1 to recite new functional limitations for the inflating memory CD8+ T cell response.
New 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 comple