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 .
Election/Restrictions
Applicant’s election with traverse of Group I, claims 1, 8, 10, 17, 22, 25, 27, 34, 35, 37, 40, 44, and 47-50, and species election of : IL-7 comprising SEQ ID NO:22, IL-21 comprising SEQ ID NO:20; polypeptide linker comprising SEQ ID NO:31; and fusion protein comprising SEQ ID NO:26 in the reply filed on 06/05/2026 is acknowledged.
It is noted that Applicant traverses the identification of groups noting that only claim 66 is drawn to a method of making a fusion protein, and claims 67-70 all directly or indirectly depend from claim 1 and are like the other claims in Group I - drawn to a fusion protein. Accordingly, Applicant requested that the office to join claims 67-70 with Group I. In response to this traverse, the office agrees with Applicant that claims 67-70 should be joined with Group I. Therefore, claims 1, 8, 10, 22, 25, 27, 34, 35, 37, 40, 44, 47-50, and 67-70 are currently under examination.
Claims 54-56, and 66 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 06/05/2026.
Claims 1, 8, 10, 22, 25, 27, 34, 35, 37, 40, 44, 47-50, and 67-70 are currently under examination.
Priority
Applicant’s claim for the benefit of a prior-filed application provisional application 63255635, filed on 10/14/2021 under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, or 365(c) is acknowledged.
Information Disclosure Statement
The information disclosure statement (IDS) was filed before the mailing date of the non-final first action on the merits. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, 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 text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
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 1, 8, 10, 34, 35, 37, 40, 44, 47-50, and 67-69 are rejected under 35 U.S.C. 103 as being unpatentable over Gu et al ( Scientific Reports, 2016) in view of Galipeau et al (CA 2355675C/PCT/US2012/064769), Charych et al ( US 2019/0290733 A1), and Weiner et al ( US 2017/0232100 A1).
Regarding claims 1,8, 34-35, 40, and 47, Gu et al teach genetically engineered whole cell cancer vaccines that co-express IL-7 and IL-21. Gu et al demonstrate that the simultaneous expression of IL-7 and IL-21 produces enhanced antitumor immunity compared with expression of either cytokine alone. Specifically, Gu et al disclose increased CD4 and CD8 T-cell responses, improved effector-memory T-cell generation, and superior tumor inhibition resulting from the co-expression of IL-7 and IL-21. Therefore, Gu et al teach the desirability of administering IL-7 and IL-21 together in order to obtain enhanced therapeutic efficacy. ( See abstract, Fig.2F, Fig.3.and Fig.5)
It is submitted that Gu et al teach the simultaneous but separate delivery of IL-7 and IL-21. This differs from the instant claims which recite the construction of a fusion protein comprising IL-7 and IL-21 linked via a polypeptide linker.
Galipeau et al supplement Gu by teaching a recombinant cytokine fusion proteins comprising IL-7 fused to another cytokine (GM-CSF) through a linker. Galipeau et al further teach nucleic acids encoding such fusion proteins, recombinant expression, a viral vector comprising the recited nucleic acid, a mammalian cell line expressing the nucleic acid, and therapeutic use of the resulting cytokine fusion protein. Galipeau, therefore, teaches that IL-7 may be incorporated into recombinant fusion protein using a peptide linker while retaining therapeutic utility.( See page 8 (lines 27-32), page 9 (lines 30-33).
Taken together, it would have prima facie obvious to one with ordinary skill in the art at the time the invention was filed to modify the construct of Galipeau et al by replacing GM-CSF with IL-21 in view of the teachings of Gu et al. Because Gu et al expressly identify IL-7 and IL-21 as a superior cytokine combination for stimulating antitumor immunity. Galipeau et al teach that IL-7 maybe fused to another cytokine by a linker to produce a single recombinant therapeutic molecule. Thus, one with ordinary skill in the art would have recognized that employing a fusion protein rather than separate expression of a cytokines provides known advantages, including coordinated delivery of both cytokines, simplified manufacturing, and ensuring the simultaneous exposure of immune cells to both cytokine. One would have had a reasonable expectation of success that replacing the GM-CSF in the construct of Galipeau et al with IL-21 would produce a fusion protein capable of co-delivering both cytokines.
It is also noted that Gu et al teach a whole cell cancer vaccine genetically modified to co-express murine IL-7 and murine IL-21, specifically stating that the coding sequences of murine IL-7/21 were amplified from C57BL/6 spleen cDNA. ( See Gu et al section “ Plasmid construction” on page 8). This differs from the selected species of instant claim which require nucleic acid encoding human IL-7 and human IL-21.
Charych et al supplement Gu et al by disclosing a human IL-7 polypeptide, wherein the amino acid sequence disclosed as SEQ ID NO:1 shares 100% sequence identity to SEQ ID NO:22 of the instant application. Accordingly, Charych expressly teaches the claimed human IL-7 sequence.
Weiner et al further supplement Gu et al by disclosing a human IL-21 polypeptide, wherein the amino acid sequence disclosed as SEQ ID NO:4 shares 100% sequence identity to SEQ ID NO:20 of the instant application. Accordingly, Weiner expressly teaches the claimed human IL-21 sequence.
Taken together, it would have been prima facie obvious to one with ordinary skill in the art at the time the invention was filed to substitute the known human IL-7 and human IL-21 coding sequences taught by Charych and Weiner, respectively, for the corresponding murine cytokine sequences disclosed by Gu et al. Because Gu et al teach that co-expression of IL-7/21 in whole cell cancer vaccines produces enhanced antitumor immunity and expressly state that the results warrant future development of IL-21 and IL-7 co-expressing whole-cell cancer vaccines ( see abstract). In other words, Gu et al provide a proof-of principle studies using murine IL7/IL 21 in mouse tumor models. However, when preparing vaccines intended for human use, a person with ordinary skill in the art would have recognized that substitution of the human orthologs for the murine sequences would have yielded the expected expression of human IL-7 and human IL-21 while maintaining the immunostimulatory strategy taught by Gu et al, thereby providing a reasonable expectation of success.
Regarding claim 10, following the discussion above, Galipeau et al further state that “Where secretion of the fusion protein is desired, appropriate secretion signals are incorporated into the vector, and that the signal sequence can be endogenous to the fusion protein or heterologous to both entities involved in the fusion protein”. ( See Galipeau et al page 43 (lines 17-20). Accordingly, Galipeau et al teach the additional limitation that the fusion protein comprises a signal sequence, as recited in claim 10.
Regarding claim 37, following the discussion above, Galipeau et al further state that “In certain embodiments, the disclosure contemplates uses of conjugates disclosed herein in autologous immune enhancement therapy (AIET), in which immune or cancer cells, e.g., lymphokine-activated killer (LAK) cells, natural killer (NK) cells, cytotoxic T lymphocytes(CTLs ), dendritic cells(DCs ), which are taken out from the body of a subject, cultured and processed ,and then the cells are put back in the body”.( See page 24 (lines 6-11). Accordingly, Galipeau et al teach the additional limitation that the genetically modified cell maybe an immune cell as recited in the instant claim.
Regarding claims, 44, and 48-50, following the discussion of claim 1 and 34 above, Gu et al in view of Galipeau et al render obvious the claimed nucleic acid encoding the fusion protein comprising of human IL7 and IL-21 linked via a polypeptide linker. Galipeau et al further teach that the nucleic acid can be incorporated into a viral vector, including poxviral vectors such as vaccinia virus, this reads on claim 50. ( See Galipeau et al pages 25 (lines 5-15) and 39 (lines 4-5)). Galipeau et al further teach that the claimed viral particle may comprise one or more transgene (i.e. payload), and disclose that suitable payloads may include tumor associated antigen/cancer markers (e.g., PSA and PAP), and other antigenic payload, this reads on claims 47-48. (See page 5 (lines 4-25), and page 43 (lines 22-33). Accordingly, Galipeau et al teach a payload falling within the claimed group of a tumor antigen. As such, it would have been obvious to employ such therapeutic payload in the viral vector of instant claims because Galipeau et al teach that they enhance immune responses and provide antitumor therapeutic.
Regarding claims 67-69, following the discussion of claim 1 above, the combined teachings of Gu et al in view of the cited prior arts render obvious claim 1. Galipeau et al further teach a membrane-bound fusion protein comprising an anchoring peptide operably linked to the fusion protein, wherein the anchoring peptide comprises a GPI anchor peptide that directs membrane localization of the fusion protein. Specifically, Galipeau et al state that “ the disclosed conjugates maybe incorporated into the surfaces of membrane particles, including cells, liposomes, micelles, vesicles, bilayer structures, virosomes, and virus-like particles , and further teach that the conjugates may be linked to lipophilic moieties, e.g., fatty acids and GPI”. Galipeau et al further teach the incorporation of GPI-anchored conjugate comprising GPI, GM-CSF, IL-7, and teaches incorporation of GPI-anchored co-stimulatory molecules into cell membranes. Galipeau et al additionally explains that cancer cells may be modified by incorporating GPI-anchored co-stimulatory molecules into tumor cell membranes prior to administration, thereby demonstrating the use of GPI as a membrane-targeting anchor for membrane associated proteins. ( See page 5 (lines 5-12) and page 25 (lines 26-31). Accordingly, Galipeau et al teach a membrane-bound fusion protein comprising an anchoring peptide, wherein the anchoring peptide is GPI, which would direct the localization of the fusion protein to a membrane surface. As such, it would have been obvious to modify the fusion protein construct to include GPI as taught by Galipeau et al because Galipeau et al expressly teach that GPI serves as a membrane anchoring moiety for fusion protein and enables their incorporation into membrane structures, including cell membrane, vesicles, and virus-like particle. There is a reasonable expectation of success that incorporating the GPI into the fusion protein of instant claim would achieve the predictable benefit of membrane association for improved biological activity.
Claim(s) 22, 25, 27, and 70 is/are rejected under 35 U.S.C. 103 as being unpatentable over Gu et in view of Galipeau et al, Charych et al, and Weiner et al as applied to claim 1,8,10, 34-35,37, 40,44, 47-50, and 67-69 above, and further in view of Guo et al ( US 2020/0000862 A1) .
Regarding claim 22, following the discussion of claim 1 above Gu et al in view of Galipeau et al, Charych et al, and Weiner render obvious claim 1. However, none of the cited prior art disclose the claimed polypeptide linker sequence comprising of ID NO:31. Guo et al supplement Gu by teaching the specific rigid peptide linker A(EA3K)4AAA) ( Guo et al SEQ ID NO: 36), which is identical to the amino acid sequence recited in Applicant’s SEQ ID NO:31. Guo et al teach utilizing that linker in fusion protein to join functional protein domains. ( See Guo et al [0130]). Therefore, it would have been prima facie obvious to one with ordinary skill in the art to employ the known rigid linker of Guo et al in the fusion protein of Gu and Galipeau because Guo et al teach that the linker is suitable for connecting functional protein domains in fusion constructs while maintaining their intended function. Thus selecting a known linker for that purpose would have been a routine design choice with a reasonable expectation of success.
Regarding claims 25 and 27, following the discussion of claims 1 and 22 above. Gu in view of Galipeau, Charych, Weiner, and Guo et al render obvious the claimed fusion protein. It should be noted that Applicant elected SEQ ID NO:26 as a representing species for the claimed fusion protein. However, it is noted that SEQ ID 26 comprises the known native IL-21 signal peptide at its N-terminus, followed by the known human IL-21 amino acid sequence taught by Weiner et al ( i.e. Applicants SEQ ID 20- as discussed above); the known rigid linker sequence taught by Guo et al ( i.e. Applicant’s SEQ ID 31) ; and the known human IL-7 amino acid sequence taught by Charych et al ( i.e. Applicants SEQ ID 22), arranged in the obvious fusion protein discussed above. It should also be noted that Galipeau et al expressly teach that cytokine fusion proteins typically comprises an N-terminal signal peptide and specifically teach that the endogenous signal peptide naturally present in the cytokine located at the N-terminus of the fusion protein maybe used to promote secretion. (See Galipeau et al page 12, lines 26-31). Accordingly, it would have been prima facie obvious to one with ordinary skill in the art at the time the invention was filed to employ the native IL-21 signal peptide as the N-terminal signal peptide of the obvious IL21/IL7 fusion protein discussed above, because Galipeau et al expressly teach using endogenous signal peptide of the N-terminal cytokine to facilitate secretion of recombinant cytokine fusion protein. Accordingly, in view of Gu et al, Galipeau et al, Charych et al, Weiner et al, and Guo et al, selection and assembly of these known amino acid sequences ( i.e. the known native IL-21 signal peptide, the known human IL-21 amino acid sequence, the known rigid linker sequence, and the known human IL-7) to produce the recombinant fusion protein would have been a routine exercise of recombinant protein design and with a reasonable expectation of success. Therefore, the recitation of SEQ ID NO:26 does not patentably distinguish the claimed fusion protein from the obvious fusion protein rendered by the cited references.
Regarding claim 70, following the discussion of claims 22 and 68 above, Gu et al in view of Galipeau render obvious a fusion protein further comprising GPI. However, neither Gu nor Galipeau teach GPI with a sequence identical to SEQ IF NO. 51 recited in instant claim. Guo et al supplement Gu and Galipeau by teaching a GPI peptide having an amino sequence of SEQ ID NO.11. ( See Guo et al paragraphs [0117], [0125], and [0138]) . It should be noted that SEQ ID NO.11 shares 100% sequence identity to SEQ ID NO:51 of the instant application. Accordingly, Guo et al expressly teach the claimed GPI sequence, and claim 70 would have been obvious over the combination of Gu, Galipeau, and Guo et al.
Conclusion
No claim is allowed.
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/FATIMAH KHALAF MATALKAH/Examiner, Art Unit 1638
/Tracy Vivlemore/Supervisory Primary Examiner, Art Unit 1638
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