DETAILED ACTION
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
2. Amendment after Non-final office action filed on 4/7/2026 is acknowledged.
3. Please do NOT enter the amendment to the specification filed on 4/7/2026. In the instant case, certain page number and/or line numbers in the amended specification filed on 4/7/2026 are inconsistent with the clean copy of the specification filed on 8/14/2023. Therefore, the amendment to the specification filed on 4/7/2026 is not entered.
4. Claim filed on 4/7/2026 is acknowledged.
5. Claim 3 has been cancelled.
6. Claims 1, 2 and 4-13 are pending in this application.
7. Claims 5-13 remain withdrawn from consideration pursuant to 37 CFR 1.142(b), as being drawn to non-elected inventions, there being no allowable generic or linking claim.
8. Applicant elected without traverse of Group 1 (claims 1-4) and elected of (a) N-terminal in claim 1 and (b) SEQ ID NO: 3 in claim 3 as species of ferritin nanocage in the reply filed on 11/25/2025. Since the elected species of ferritin nanocage is not a species, the Examiner telephoned Applicant’s representative, Hyun Yong Lee, on 12/9/2025 for further species election. And Applicant’s representative elected on the phone that the ferritin nanocage formed by PpNF disclosed in instant Figure 1 as the elected species of ferritin nanocage.
Restriction requirement was deemed proper and made FINAL in the previous office action. Group 1 is drawn to a ferritin nanocage comprising a fusion polypeptide, wherein the fusion polypeptide is a programmed death-ligand 1 (PD-L1)-binding peptide consisting of the amino acid sequence of SEQ ID NO: 2 conjugated to a N-terminus of a human ferritin heavy chain fragment consisting of the amino acid sequence of SEQ ID NO: 1. A search was conducted on the elected species; and prior art was found. Claims 1, 2 and 4 are examined on the merits in this office action.
Please note: Due to Applicant’s amendment to the claim, the ferritin nanocage formed by PpNF disclosed in instant Figure 1 as the elected species of ferritin nanocage does not read on instant claims 1 and 4.
Priority
9. The application is a CIP of PCT/KR2021/014261 filed on 10/14/2021, which claims foreign priority to REPUBLIC OF KOREA application No. 10-2020-0138075 filed on 10/23/2020. The filing date of the priority document has been perfected; and REPUBLIC OF KOREA application No. 10-2020-0138075 provides support to instant claims 1, 2 and 4. Therefore, the effective filing date of instant claims 1, 2 and 4 is 10/23/2020.
Withdrawn Objections and Rejections
10. Objection to claims 3 and 4 is hereby withdrawn in view of Applicant’s amendment to the claim.
11. Rejection to claims 1-4 under 35 U.S.C. 102(a)(1) as being anticipated by Jeon et al (Biomaterials, 2021, 270, pages 1-15, available online on 1/22/2021), and as evidenced by the ferritin heavy chain [Homo sapiens] document (2025, from https://www.ncbi.nlm.nih.gov/protein/NP_002023.2?report=genbank&log$=prottop&blast_rank=3&RID=KKBA9RXC014, pages 1-3) and rejection to claims 1-4 on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 1-8 of US patent 11306119 B2 in view of Jeon et al above and as evidenced by the ferritin heavy chain [Homo sapiens] document above are hereby withdrawn in view of the filing date of the priority document has been perfected, which disqualifies Jeon et al as a prior art reference.
Maintained/Revised Objections
12. The specification remains objected to for the following minor informality: The specification recites “SEQ ID NO: 3 (GG)” on page 7, line 13 of instant specification. Based on the sequence listing filed on 8/14/2023, Applicant is suggested to amend this recitation as “GG”.
Please note: the specification has not been checked to the extent necessary to determine the presence of all possible error. Applicant's cooperation is required in correcting any errors of which applicant may become aware in the specification (see MPEP § 608.01).
13. The drawings remain objected to for the following minor informality:
Figures 1-13: The quality of these figures are extremely poor. Applicant is required to provide clear images of these figures.
Figures 5, 7 and 8: Each of these figures contains multiple figures. For example, Figure 5 contains 5A-5D; and each of Figures 5A-5D needs its individual description of the drawings. This also applies to Figures 7 and 8.
Figures 10 and 11 are described with respect to color. Reference to specific colors in the description of the drawings should be removed.
Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
14. (Revised due to Applicant’s amendment to the claim) Claim 1 remains objected to for the following minor informality: Applicant is suggested to amend claim 1 as “…a programmed death-ligand 1 (PD-L1)-binding peptide consisting of the amino acid sequence of SEQ ID NO: 2 conjugated to N-terminus of a human ferritin heavy chain fragment…”.
Response to Applicant's Arguments
15. With regards to the amendment to the specification filed on 4/7/2026, as stated in Section 3 above, the amendment to the specification filed on 4/7/2026 is not entered. Therefore, the objection to the specification is hereby maintained.
With regards to the amendment to the drawings filed on 4/7/2026, the quality of Figures 1-13 remain extremely poor. Furthermore, in view of the amendment to the specification filed on 4/7/2026 not being entered, the objection to the drawings is hereby maintained.
Furthermore, Applicant’s amendment to claim 1 introduces additional minor issues into claim 1. Therefore, the objection is hereby maintained.
Maintained/Revised Rejections
Claim Rejections - 35 U.S.C. § 103
16. The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102 of this title, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
17. The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
18. (Revised due to Applicant’s amendment to the claim) Claims 1 and 4 remain rejected under 35 U.S.C. 103 as being unpatentable over Nam et al (US 2019/0216947 A1, cited and enclosed in the previous office action) in view of Lee et al (WO 2019117690 A1, filed with IDS, a clear copy of the machine translation is used and enclosed in the previous office action, pages 1-42) and Kim et al (US 2018/0291072 A1, filed with IDS).
The instant claims 1 and 4 are drawn to a ferritin nanocage comprising a fusion polypeptide, wherein the fusion polypeptide is a programmed death-ligand 1 (PD-L1)-binding peptide consisting of the amino acid sequence of SEQ ID NO: 2 conjugated to a N-terminus of a human ferritin heavy chain fragment consisting of the amino acid sequence of SEQ ID NO: 1.
Nam et al, throughout the patent, teach ferritin nanocage formed by self-assembly of a fusion protein comprising a phagocytosis enhancing protein SIRPα or SIRPγ and a ferritin heavy chain protein and a second fusion protein comprising a ferritin heavy chain protein and a single chain-based antibody targeting PD-1/PD-L1 as an immunotherapeutic agent; wherein the single chain-based antibody targeting PD-1/PD-L1 is on the outer surface of the ferritin nanocage; and wherein the SIRPα or SIRPγ is linked to the N-terminal or C-terminal of the ferritin heavy chain protein, for example, Abstract; Figure 1B; page 1, paragraph [0014]; page 9, paragraph [0098]; and claim 18. It meets the limitation of instant claim 4.
The difference between the reference and instant claims 1 and 4 is that the reference does not teach the fusion polypeptide recited in instant claims.
However, Lee et al, throughout the patent, teach a peptide that binds to PD-L1 and its use in cancer immunotherapy; wherein such peptide blocks the interaction between PD-1 and its ligand PD-L1, and in comparison to antibodies that block the PD-1/PD-L1 pathway, it is a highly effective and low-cost inhibitor of PD-1 and PD-L1; and wherein such peptide can be PD-L1Pep-1 consisting of the amino acid sequence CLQKTPKQC (identical to the PD-L1-binding peptide of instant SEQ ID NO: 2), for example, pages 1-2, paragraphs [0001]; [0002] and [0004]; and page 25, paragraph [0085].
Furthermore, Kim et al, throughout the patent, teach a human-derived ferritin monomer fragment and a fusion polypeptide in which a polypeptide or a protein is fused to the N- or a C-terminus of the ferritin monomer fragment; wherein the human-derived ferritin monomer fragment is short Ferritin H consisting of the amino acid sequence of SEQ ID NO: 2 (identical to the human ferritin heavy chain fragment of instant SEQ ID NO: 1); and wherein in comparison to the wild-type human ferritin heavy chain, the short Ferritin H has various advantages, including a steric hindrance is so alleviated that the limitation on the size of a peptide or a protein that can be fused to the C-terminus is eliminated, for example, Abstract; page 1, paragraphs [0001], [0009] and [0010]; and page 3, paragraphs [0041] and [0047].
Therefore, it would have been obvious to one of ordinary skilled in the art to combine the teachings of Nam et al, Lee et al and Kim et al to develop a ferritin nanocage comprising a fusion polypeptide, wherein the fusion polypeptide is PD-L1Pep-1 consisting of the amino acid sequence CLQKTPKQC (identical to the PD-L1-binding peptide of instant SEQ ID NO: 2) conjugated to the N-terminus of the short Ferritin H consisting of the amino acid sequence of SEQ ID NO: 2 in Kim et al (identical to the human ferritin heavy chain fragment of instant SEQ ID NO: 1), and wherein the PD-L1Pep-1 is on the outer surface of the ferritin nanocage.
One of ordinary skilled in the art would have been motivated to combine the teachings of Nam et al, Lee et al and Kim et al to develop a ferritin nanocage comprising a fusion polypeptide, wherein the fusion polypeptide is PD-L1Pep-1 consisting of the amino acid sequence CLQKTPKQC (identical to the PD-L1-binding peptide of instant SEQ ID NO: 2) conjugated to the N-terminus of the short Ferritin H consisting of the amino acid sequence of SEQ ID NO: 2 in Kim et al (identical to the human ferritin heavy chain fragment of instant SEQ ID NO: 1), and wherein the PD-L1Pep-1 is on the outer surface of the ferritin nanocage, because Lee et al, throughout the patent, teach a peptide that binds to PD-L1 and its use in cancer immunotherapy; wherein such peptide blocks the interaction between PD-1 and its ligand PD-L1, and in comparison to antibodies that block the PD-1/PD-L1 pathway, it is a highly effective and low-cost inhibitor of PD-1 and PD-L1; and wherein such peptide can be PD-L1Pep-1 consisting of the amino acid sequence CLQKTPKQC (identical to the PD-L1-binding peptide of instant SEQ ID NO: 2). Kim et al, throughout the patent, teach a human-derived ferritin monomer fragment and a fusion polypeptide in which a polypeptide or a protein is fused to the N- or a C-terminus of the ferritin monomer fragment optionally via a linker; wherein the human-derived ferritin monomer fragment is short Ferritin H consisting of the amino acid sequence of SEQ ID NO: 2 (identical to the human ferritin heavy chain fragment of instant SEQ ID NO: 1); and wherein in comparison to the wild-type human ferritin heavy chain, the short Ferritin H has various advantages.
A person of ordinary skilled in the art would have reasonable expectation of success in combining the teachings of Nam et al, Lee et al and Kim et al to develop a ferritin nanocage comprising a fusion polypeptide, wherein the fusion polypeptide is PD-L1Pep-1 consisting of the amino acid sequence CLQKTPKQC (identical to the PD-L1-binding peptide of instant SEQ ID NO: 2) conjugated to the N-terminus of the short Ferritin H consisting of the amino acid sequence of SEQ ID NO: 2 in Kim et al (identical to the human ferritin heavy chain fragment of instant SEQ ID NO: 1), and wherein the PD-L1Pep-1 is on the outer surface of the ferritin nanocage.
Response to Applicant's Arguments
19. Applicant argues about each of the cited prior art references individually. Applicant further argues that “There Is No Proper Motivation to Combine the Teachings of Nam, Lee, and Kim”. Applicant also argues that “The Claimed Invention Exhibits Unexpected Results”.
20. Applicant's arguments have been fully considered but have not been found persuasive.
In response to Applicant's arguments about instant rejection, the Examiner agrees that none of the cited references individually teaches or suggests the ferritin nanocage recited in instant claims 1 and 4; and none of the cited references anticipates the ferritin nanocage recited in instant claims 1 and 4. However, the Examiner would like to point out that instant claims 1 and 4 are rejected under 35 U.S.C. 103 (obviousness type), and the rejection is based on the combined teachings of Nam et al, Lee et al and Kim et al, it is not necessary for each of the cited references to teach all the limitations of instant claims. Furthermore, the Examiner would like to point out that the MPEP states "One cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references…" (see MPEP § 2145 IV).
In response to Applicant's arguments about instant rejection, the Examiner understands that Nam et al do not teach the ferritin nanocage recited in instant claims 1 and 4. However, in the instant case, as stated in Section 18 above, Nam et al explicitly teach ferritin nanocage formed by self-assembly of a fusion protein comprising a phagocytosis enhancing protein SIRPα or SIRPγ and a ferritin heavy chain protein and a second fusion protein comprising a ferritin heavy chain protein and a single chain-based antibody targeting PD-1/PD-L1 as an immunotherapeutic agent; wherein the single chain-based antibody targeting PD-1/PD-L1 is on the outer surface of the ferritin nanocage; and wherein the SIRPα or SIRPγ is linked to the N-terminal or C-terminal of the ferritin heavy chain protein. Furthermore, Lee et al explicilty teach peptide PD-L1Pep-1 that binds to PD-L1 (identical to the PD-L1-binding peptide of instant SEQ ID NO: 2) and its use in cancer immunotherapy; wherein such peptide blocks the interaction between PD-1 and its ligand PD-L1, and in comparison to antibodies that block the PD-1/PD-L1 pathway, it is a highly effective and low-cost inhibitor of PD-1 and PD-L1. Therefore, in view of the teachings of Lee et al, it would have been obvious to one of ordinary skilled in the art, and/or one of ordinary skilled in the art would have been motivated to replace the single chain-based antibody targeting PD-1/PD-L1 in the fusion protein in Nam et al with the peptide PD-L1Pep-1 in Lee et al. In addition, Kim et al explicitly teach a human-derived ferritin monomer fragment and a fusion polypeptide in which a polypeptide or a protein is fused to the N- or a C-terminus of the ferritin monomer fragment; wherein the human-derived ferritin monomer fragment is short Ferritin H consisting of the amino acid sequence of SEQ ID NO: 2 (identical to the human ferritin heavy chain fragment of instant SEQ ID NO: 1); and wherein in comparison to the wild-type human ferritin heavy chain, the short Ferritin H has various advantages, including a steric hindrance is so alleviated that the limitation on the size of a peptide or a protein that can be fused to the C-terminus is eliminated. Therefore, in view of the combined teachings of Nam et al, Lee et al and Kim et al as set forth in Section 18 above, it would have been obvious to one of ordinary skilled in the art, and/or one of ordinary skilled in the art would have been motivated to develop the ferritin nanocage recited in instant claims 1 and 4.
With regards to Applicant’s arguments about impermissible hindsight, in the instant case, Applicant fails to point to any facet of instant rejection that is not found in the cited prior art references. It is unclear to the Examiner which part of the instant rejection is not based on the combined teachings of the cited references. Merely pointing out the differences between each of the cited references and instant claimed invention is not proof of hindsight reasoning. Furthermore, the MPEP states “"[a]ny judgment on obviousness is in a sense necessarily a reconstruction based on hindsight reasoning, but so long as it takes into account only knowledge which was within the level of ordinary skill in the art at the time the claimed invention was made and does not include knowledge gleaned only from applicant’s disclosure, such a reconstruction is proper." In re McLaughlin, 443 F.2d 1392, 1395, 170 USPQ 209, 212 (CCPA 1971).” (see MPEP § 2145).
With regards to Applicant’s arguments that Nam would actually teach away from the claimed combination, the Examiner understands that the single chain-based antibody targeting PD-1/PD-L1 in Nam et al is not the same as the peptide PD-L1Pep-1 that binds to PD-L1 in Lee et al. However, in the instant case, it is unclear to the Examiner how and/or why this means and/or equals to Nam would actually teach away from the claimed combination. Further clarification is required.
In response to Applicant’s arguments that “The Claimed Invention Exhibits Unexpected Results”:
First, the Examiner would like to bring Applicant’s attention to MPEP § 716.02, which provides guidance on allegations of unexpected results. As stated in MPEP: “An affidavit or declaration under 37 CFR 1.132 must compare the claimed subject matter with the closest prior art to be effective to rebut a prima facie case of obviousness.” (see MPEP § 716.02(e)). In the instant case, the closest prior art is the cited Nam et al reference. Therefore, the comparison for unexpected results should be made between the ferritin nanocage in the cited Nam et al reference and instant claimed ferritin nanocage (see MPEP § 716.02(e)). Furthermore, as stated in MPEP: “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." (see MPEP § 716.02(d)). In the instant case, PpNF disclosed in instant Application does not meet the limitations of the ferritin nanocage recited in instant claims 1 and 4; and PpCF disclosed in instant Application does not meet the limitations of the ferritin nanocage recited in instant claims 1, 2 and 4.
Second, in the instant case, in view of the teachings of both Nam et al and Kim et al, one of ordinary skilled in the art would understand that for a fusion protein comprising human ferritin heavy chain fragment, the human ferritin heavy chain fragment can be at either the N- or a C-terminus of the fusion protein. One of ordinary skilled in the art would understand and reasonably expect that a fusion protein comprising human ferritin heavy chain fragment at the N-terminus of the fusion protein would not behave the same as a fusion protein comprising human ferritin heavy chain fragment at the C-terminus of the fusion protein. Therefore, it is unclear to the Examiner why and/or how the results regarding PpNF and PpCF are unexpected.
Third, the Examiner would like to point out that the difference between PpNF and PpCF is more than just the position of the human ferritin heavy chain fragment in the fusion polypeptide. The linkers in PpNF and PpCF are not the same. Therefore, one of ordinary skilled in the art would not be able to reach the conclusion that the results regarding PpNF and PpCF are completely due to the position of the human ferritin heavy chain fragment in the fusion polypeptide; and such difference could be due to the linker in these fusion polypeptides.
Taken all these together, the rejection is deemed proper and is hereby maintained.
21. (Revised due to Applicant’s amendment to the claim) Claim 2 remains rejected under 35 U.S.C. 103 as being unpatentable over Nam et al (US 2019/0216947 A1, cited and enclosed in the previous office action) in view of Lee et al (WO 2019117690 A1, filed with IDS, a clear copy of the machine translation is used and enclosed in the previous office action, pages 1-42), Kim et al (US 2018/0291072 A1, filed with IDS) and Meyer (EP1884521 A1, cited and enclosed in the previous office action).
The instant claim 2 is drawn to a ferritin nanocage comprising a fusion polypeptide, wherein the fusion polypeptide is a programmed death-ligand 1 (PD-L1)-binding peptide consisting of the amino acid sequence of SEQ ID NO: 2 conjugated to a N-terminus of a human ferritin heavy chain fragment consisting of the amino acid sequence of SEQ ID NO: 1, and wherein the fusion polypeptide further comprises a linker consisting of the amino acid sequence GG between the human ferritin heavy chain fragment and the PD-L1-binding peptide.
Nam et al, throughout the patent, teach ferritin nanocage formed by self-assembly of a fusion protein comprising a phagocytosis enhancing protein SIRPα or SIRPγ and a ferritin heavy chain protein and a second fusion protein comprising a ferritin heavy chain protein and a single chain-based antibody targeting PD-1/PD-L1 as an immunotherapeutic agent; wherein the single chain-based antibody targeting PD-1/PD-L1 is on the outer surface of the ferritin nanocage; and wherein the SIRPα or SIRPγ is linked to the N-terminal or C-terminal of the ferritin heavy chain protein, for example, Abstract; Figure 1B; page 1, paragraph [0014]; page 9, paragraph [0098]; and claim 18. Nam et al further teach a linker is presented in the fusion proteins, wherein the linker is selected from the group consisting of (G4S)n, (GSSGGS)n and SEQ ID NOS: 65-81, for example, page 4, paragraph [0039]; and page 5, paragraph [0048].
The difference between the reference and instant claim 2 is that the reference does not teach the ferritin nanocage formed by PpNF disclosed in instant Figure 1 as the elected species of ferritin nanocage and the limitation of instant claim 2.
However, Lee et al, throughout the patent, teach a peptide that binds to PD-L1 and its use in cancer immunotherapy; wherein such peptide blocks the interaction between PD-1 and its ligand PD-L1, and in comparison to antibodies that block the PD-1/PD-L1 pathway, it is a highly effective and low-cost inhibitor of PD-1 and PD-L1; and wherein such peptide can be PD-L1Pep-1 consisting of the amino acid sequence CLQKTPKQC (identical to the PD-L1-binding peptide of instant SEQ ID NO: 2), for example, pages 1-2, paragraphs [0001]; [0002] and [0004]; and page 25, paragraph [0085].
Furthermore, Kim et al, throughout the patent, teach a human-derived ferritin monomer fragment and a fusion polypeptide in which a polypeptide or a protein is fused to the N- or a C-terminus of the ferritin monomer fragment optionally via a linker; wherein the human-derived ferritin monomer fragment is short Ferritin H consisting of the amino acid sequence of SEQ ID NO: 2 (identical to the human ferritin heavy chain fragment of instant SEQ ID NO: 1); and wherein in comparison to the wild-type human ferritin heavy chain, the short Ferritin H has various advantages, including a steric hindrance is so alleviated that the limitation on the size of a peptide or a protein that can be fused to the C-terminus is eliminated, for example, Abstract; page 1, paragraphs [0001], [0009] and [0010]; and page 3, paragraphs [0041] and [0047].
In addition, Meyer teaches GG as a peptide linker that can be used in fusion protein/polypeptide, for example, page 6, paragraph [0022].
Therefore, it would have been obvious to one of ordinary skilled in the art to combine the teachings of Nam et al, Lee et al, Kim et al and Meyer to develop a ferritin nanocage comprising a fusion polypeptide, wherein the fusion polypeptide is PD-L1Pep-1 consisting of the amino acid sequence CLQKTPKQC (identical to the PD-L1-binding peptide of instant SEQ ID NO: 2) conjugated to the N-terminus of the short Ferritin H consisting of the amino acid sequence of SEQ ID NO: 2 in Kim et al (identical to the human ferritin heavy chain fragment of instant SEQ ID NO: 1) via a linker consisting of the amino acid sequence GG, and wherein the PD-L1Pep-1 is on the outer surface of the ferritin nanocage. It reads on the ferritin nanocage formed by PpNF disclosed in instant Figure 1 as the elected species of ferritin nanocage.
One of ordinary skilled in the art would have been motivated to combine the teachings of Nam et al, Lee et al, Kim et al and Meyer to develop a ferritin nanocage comprising a fusion polypeptide, wherein the fusion polypeptide is PD-L1Pep-1 consisting of the amino acid sequence CLQKTPKQC (identical to the PD-L1-binding peptide of instant SEQ ID NO: 2) conjugated to the N-terminus of the short Ferritin H consisting of the amino acid sequence of SEQ ID NO: 2 in Kim et al (identical to the human ferritin heavy chain fragment of instant SEQ ID NO: 1) via a linker consisting of the amino acid sequence GG, and wherein the PD-L1Pep-1 is on the outer surface of the ferritin nanocage, because Lee et al, throughout the patent, teach a peptide that binds to PD-L1 and its use in cancer immunotherapy; wherein such peptide blocks the interaction between PD-1 and its ligand PD-L1, and in comparison to antibodies that block the PD-1/PD-L1 pathway, it is a highly effective and low-cost inhibitor of PD-1 and PD-L1; and wherein such peptide can be PD-L1Pep-1 consisting of the amino acid sequence CLQKTPKQC (identical to the PD-L1-binding peptide of instant SEQ ID NO: 2). Kim et al, throughout the patent, teach a human-derived ferritin monomer fragment and a fusion polypeptide in which a polypeptide or a protein is fused to the N- or a C-terminus of the ferritin monomer fragment optionally via a linker; wherein the human-derived ferritin monomer fragment is short Ferritin H consisting of the amino acid sequence of SEQ ID NO: 2 (identical to the human ferritin heavy chain fragment of instant SEQ ID NO: 1); and wherein in comparison to the wild-type human ferritin heavy chain, the short Ferritin H has various advantages. And Meyer teaches GG as a peptide linker that can be used in fusion protein/polypeptide.
A person of ordinary skilled in the art would have reasonable expectation of success in combining the teachings of Nam et al, Lee et al, Kim et al and Meyer to develop a ferritin nanocage comprising a fusion polypeptide, wherein the fusion polypeptide is PD-L1Pep-1 consisting of the amino acid sequence CLQKTPKQC (identical to the PD-L1-binding peptide of instant SEQ ID NO: 2) conjugated to the N-terminus of the short Ferritin H consisting of the amino acid sequence of SEQ ID NO: 2 in Kim et al (identical to the human ferritin heavy chain fragment of instant SEQ ID NO: 1) via a linker consisting of the amino acid sequence GG, and wherein the PD-L1Pep-1 is on the outer surface of the ferritin nanocage.
Response to Applicant's Arguments
22. Applicant presents the same arguments about the recited Nam et al, Lee et al, Kim et al references. Applicant further argues that Meyer is non-analogous art and there is no motivation to select GG in the linkers disclosed in Meyer.
23. Applicant's arguments have been fully considered but have not been found persuasive.
Applicant’s arguments about the recited Nam et al, Lee et al, Kim et al references have been addressed in Section 20 above.
In response to Applicant's arguments about the cited Meyer reference, the Examiner understands that Meyer does not teach ferritin nanocage. However, in the instant case, both Meyer and instant application are in the same field of applying fusion protein comprising the active peptide for drug delivery. Therefore, the teachings of Meyer are reasonably pertinent to the problem faced by the inventor; and Meyer is an analogous art. With regards to Applicant’s arguments that there is no motivation to select GG in the linkers disclosed in Meyer, in the instant case, the Examiner understands that Meyer teaches the linker is an all-glycine sequence, e.g. GG, GGG, GGGG, GGGGG, etc. However, the Examiner would like to point out that the fact that there is more than one options for the linker disclosed in Meyer does not render any of these option unobvious. And in the instant case, considering Meyer explicitly teaches GG as a peptide linker that can be used in a fusion protein/polypeptide, it would have been obvious to one of ordinary skilled in the art, and/or one of ordinary skilled in the art would have been motivated to apply such linker in the fusion polypeptide developed from the combined teachings of Nam et al, Lee et al and Kim et al and develop the ferritin nanocage recited in instant claim 2.
Taken all these together, the rejection is deemed proper and is hereby maintained.
Obviousness Double Patenting
24. 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 claims at issue are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); and In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on a nonstatutory double patenting ground provided the reference application or patent either is shown to be commonly owned with this application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
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25. (Revised due to Applicant’s amendment to the claim) Claims 1 and 4 remain rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 1-8 of US patent 11306119 B2 in view of Nam et al (US 2019/0216947 A1, cited and enclosed in the previous office action), Lee et al (WO 2019117690 A1, filed with IDS, a clear copy of the machine translation is used and enclosed in the previous office action, pages 1-42) and Kim et al (US 2018/0291072 A1, filed with IDS).
26. Instant claims 1 and 4 are drawn to a ferritin nanocage comprising a fusion polypeptide, wherein the fusion polypeptide is a programmed death-ligand 1 (PD-L1)-binding peptide consisting of the amino acid sequence of SEQ ID NO: 2 conjugated to a N-terminus of a human ferritin heavy chain fragment consisting of the amino acid sequence of SEQ ID NO: 1.
27. Claims 1-8 of US patent 11306119 B2 are drawn to a peptide that specifically binds to PD-L1, consisting of the amino acid sequence of SEQ ID NO: 1 or SEQ ID NO:
2; and methods of using such peptide for diagnosing, preventing or treating cancer .
The PD-L1 binding peptide of SEQ ID NO: 1 recited in claims 1-8 of US patent 11306119 B2 is identical to the PD-L1 binding peptide of instant SEQ ID NO: 2.
28. The difference between claims 1-8 of US patent 11306119 B2 and the ferritin nanocage recited in instant claims 1 and 4 is that they do not teach fusing such PD-L1 binding peptide to the N-terminus of a human ferritin heavy chain fragment consisting of the amino acid sequence of instant SEQ ID NO: 1.
However, in view of the combined teachings of Nam et al, Lee et al and Kim et al as set forth in Section 18 above, it would have been obvious to one of ordinary skilled in the art to modify the PD-L1 binding peptide of SEQ ID NO: 1 recited in claims 1-8 of US patent 11306119 B2 and develop the ferritin nanocage recited in instant claims 1 and 4.
29. (Revised due to Applicant’s amendment to the claim) For the same and/or similar reasonings/rational as the rejection set forth in Sections 25-28 above, instant claim 2 remains rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 1-8 of US patent 11306119 B2 and in view of the combined teachings of Nam et al (US 2019/0216947 A1, cited and enclosed in the previous office action), Lee et al (WO 2019117690 A1, filed with IDS, a clear copy of the machine translation is used and enclosed in the previous office action, pages 1-42), Kim et al (US 2018/0291072 A1, filed with IDS) and Meyer (EP1884521 A1, cited and enclosed in the previous office action) as set forth in Section 21 above.
Response to Applicant's Arguments
30. Applicant argues that the instant claims are patently distinct from the claims of the ‘119 patent. Applicant further presents the same arguments about the cited references and unexpected results as presented in Section 19 above.
31. Applicant's arguments have been fully considered but have not been found persuasive.
Applicant’s arguments about the cited references and unexpected results have been addressed in Section 20 above.
In response to Applicant’s arguments that the instant claims are patently distinct from the claims of the ‘119 patent, the Examiner understands that claims of US patent 11306119 B2 are drawn to a peptide that specifically binds to PD-L1, not a ferritin nanocage recited in instant claims. However, the Examiner would like to point out that the ODP rejections are based on further in view of either the combined teachings of Nam et al, Lee et al and Kim et al as set forth in Section 18 above or the combined teachings of Nam et al, Lee et al, Kim et al and Meyer as set forth in Section 21 above.
Taken all these together, these double patenting rejections are deemed proper. And until a proper terminal disclaimer is filed and approved by the Office, these double patenting rejections are hereby maintained.
New Rejections
Claim Rejections - 35 U.S.C. § 112 paragraph (d)
32. 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 35 U.S.C. 112 (pre-AIA ), fourth paragraph:
Subject to the [fifth paragraph of 35 U.S.C. 112 (pre-AIA )], 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.
33. Claim 2 is rejected under 35 U.S.C. 112(d) or 35 U.S.C. 112 (pre-AIA ), 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. 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.
34. Claim 2 depends on claim 1; and claim 2 recites “The ferritin nanocage of claim 1, wherein the fusion polypeptide further comprises a linker consisting of the amino acid sequence GG between the human ferritin heavy chain fragment and the PD-L1-binding peptide “. However, the fusion polypeptide recited in instant claim 1 is a programmed death-ligand 1 (PD-L1)-binding peptide consisting of the amino acid sequence of SEQ ID NO: 2 conjugated to a N-terminus of a human ferritin heavy chain fragment consisting of the amino acid sequence of SEQ ID NO: 1. Therefore, the scope of the fusion polypeptide recited in instant claim 2 is broader than that of the fusion polypeptide recited in instant claim 1. Thus, claim 2 does not further limit the scope of the fusion polypeptide recited in instant claim 1; and claim 2 is improper dependent forms for failing to further limit the subject matter of claim 1.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any extension fee pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the date of this final action.
No claim is allowed.
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/LI N KOMATSU/Primary Examiner, Art Unit 1658
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