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 5/21/2026 is acknowledged.
3. Claims 1-35 are pending in this application.
4. Claims 1-15 and 32 remain withdrawn from consideration pursuant to 37 CFR 1.142(b), as being drawn to non-elected inventions, there being no allowable generic or linking claim. Claims 20-22 and 24-31 remain withdrawn from consideration as being drawn to non-elected species.
5. Applicant elected without traverse of Group 2 (claims 16-31) and elected with traverse of nitrogen mustard-based drugs as species of additional anticancer treatment; and a fusion protein of SEQ ID NO: 1 as the "programmed cell death protein 1", SEQ ID NO: 3 as the "self-assembling protein", and SEQ ID NO: 14 as the "linker" as species of protein nanocage in the reply filed on 1/16/2024. After further careful reconsideration, the species election requirement for protein nanocage for the elected Group 2 is withdrawn.
Restriction requirement was deemed proper and made FINAL in the previous office actions. Group 2 is drawn to a method of treating cancer in an individual in need thereof, wherein the method comprises intratumorally administering to the individual a pharmaceutical composition comprising nanocages formed by self-assembly of a fusion protein comprising a programmed cell death protein 1 linked to the C-terminus of a ferritin heavy chain protein, wherein the nanocages induce anti-tumor immunity activation at two immune checkpoints of an effector phase and a cognitive phase, wherein the anti-tumor immunity activation at the effector phase occurs in the tumor microenvironment (TME), wherein the anti-tumor immunity activation at the cognitive phase occurs in the tumor-draining lymph node (TDLN), wherein the nanocage is a decorated with a programmed cell death protein 1 on the surface thereof, wherein a binding ability of the nanocage to programmed death-ligand 1 (PD-L1) and programmed death-ligand 2 (PD-L2) expressed cancer cells is increased as compared with a nanocage not decorated with a programmed cell death protein 1 on the surface, and wherein the programmed cell death protein 1 comprises the amino acid sequence that is at least 70% identical to the amino acid sequence of SEQ ID NO: 1. A search was conducted on the elected species; and prior art was found for nitrogen mustard-based drugs as the elected species of additional anticancer treatment. Claims 20-22 and 24-31 remain withdrawn from consideration as being drawn to non-elected species. Claims 16-19, 23 and 33-35 are examined on the merits in this office action.
Withdrawn Objections
6. Objection to claims 16 and 34 is hereby withdrawn in view of Applicant's amendment to the claim.
Claim Interpretations
7. With regards to the fusion protein recited in instant claims, as stated in the previous office actions, instant claim 16 recites “a fusion protein comprising a programmed cell death protein 1 linked to the C-terminus of a ferritin heavy chain protein”. First, the transitional phrase “comprising” is inclusive or open-ended and does not exclude additional, unrecited elements or method step (see MPEP § 2111.03). Second, the instant specification, in particular, instant Figure 2A, discloses the instant claimed fusion protein can have extra element between the programmed cell death protein 1 and the ferritin heavy chain protein. Therefore, in the instant case, in the broadest reasonable interpretation, the Examiner is interpretating the instant claimed fusion protein comprises a programmed cell death protein 1 directly or indirectly linked to the C-terminus of a ferritin heavy chain protein.
With regards to the term “individual” recited in instant claim 16, the instant specification fails to define it. In the instant case, based on the original filed claim and the disclosure of instant specification, in the broadest reasonable interpretation, the Examiner is interpretating the term “individual” recited in instant claimed is not limited to human only.
With regards to the term “an amino acid sequence of SEQ ID NO: 1” recited in instant claim 35, based on the disclosure of instant specification, in particular the fusion protein disclosed in instant Figure 2, the term “an amino acid sequence of SEQ ID NO: 1” recited in instant claim 35 broadly includes both fragments and full-length of instant SEQ ID NO: 1. And in view of instant claim 16, such fragments need to comprise the amino acid sequence that is at least 70% identical to the amino acid sequence of instant SEQ ID NO: 1.
Maintained/Revised Rejections
Claim Rejections - 35 U.S.C. § 103
8. 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.
9. 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.
10. (Revised due to Applicant’s amendment to the claim) Claims 16-19, 23 and 33-35 remain rejected under 35 U.S.C. 103 as being unpatentable over Nam et al (US 2019/0216947 A1, filed with IDS) in view of Lázár-Molnár et al (EBioMedicine, 2017, 17, pages 30-44, cited and enclosed in the previous office actions), and as evidenced by the programmed cell death 1 [Mus musculus] document (2016, pages 1-3, from https://www.ncbi.nlm.nih.gov/protein/EDL39922.1?report=genbank&log$=protalign&blast_rank=2&RID=NEE2R4YP013, cited and enclosed in the previous office actions).
The instant claims 16-19, 23 and 33-35 are drawn to a method of treating cancer in an individual in need thereof, wherein the method comprises intratumorally administering to the individual a pharmaceutical composition comprising nanocages formed by self-assembly of a fusion protein comprising a programmed cell death protein 1 linked to the C-terminus of a ferritin heavy chain protein, wherein the nanocages induce anti-tumor immunity activation at two immune checkpoints of an effector phase and a cognitive phase, wherein the anti-tumor immunity activation at the effector phase occurs in the tumor microenvironment (TME), wherein the anti-tumor immunity activation at the cognitive phase occurs in the tumor-draining lymph node (TDLN), wherein the nanocage is a decorated with a programmed cell death protein 1 on the surface thereof, wherein a binding ability of the nanocage to programmed death-ligand 1 (PD-L1) and programmed death-ligand 2 (PD-L2) expressed cancer cells is increased as compared with a nanocage not decorated with a programmed cell death protein 1 on the surface, and wherein the programmed cell death protein 1 comprises the amino acid sequence that is at least 70% identical to the amino acid sequence of SEQ ID NO: 1.
Nam et al, throughout the patent, teach nanocage formed by self-assembly of a fusion protein comprising a phagocytosis enhancing protein linked to the C-terminus of a self-assembling protein via a linker as an immunotherapeutic agent, wherein the self-assembling protein is a ferritin heavy chain protein, wherein the linker can be SEQ ID NO: 81 consisting of the amino acid sequence GSSGGSGSSGGSGGGDEADGSRGS QKAGVDE (identical to the linker of instant SEQ ID NO: 14), and wherein the nanocage is decorated with the phagocytosis enhancing protein on its surface; a protein nanocage complex in which an immunogenic cell death inducer, such as doxorubicin, is loaded in the nanocage; and a method of treating colon cancer in mice, wherein the method comprises intratumorally administering to the mice having colon cancer a pharmaceutical composition comprising such nanocage, for example, Abstract; Figures 1 and 2; page 1, paragraphs [0005], [0012] and [0014]; page 4, paragraph [0039]; page 5, paragraph [0048]; pages 11-12, Experimental Example 3; and claims 1-21 and 25-28. It meets the limitations of the patient population, the route of administration and the ferritin heavy chain protein recited in instant claim 16; and the limitations of instant claims 17-19 and 34. Nam et al further teach the immunogenic cell death inducer can be a cyclophosphamide anticancer agent (a nitrogen mustard-based drug), for example, page 4, paragraph [0040]; page 5, paragraph [0057]; and claims 8 and 27. It reads on nitrogen mustard-based drugs as the elected species of additional anticancer treatment; and meets the limitation of instant claim 23.
The difference between the reference and instant claims 16-19, 23 and 33-35 is that the reference does not teach the nanocage and the limitation “wherein the nanocages induce anti-tumor immunity activation at two immune checkpoints of an effector phase and a cognitive phase, wherein the anti-tumor immunity activation at the effector phase occurs in the tumor microenvironment (TME), wherein the anti-tumor immunity activation at the cognitive phase occurs in the tumor-draining lymph node (TDLN), wherein the nanocage is a decorated with a programmed cell death protein 1 on the surface thereof, wherein a binding ability of the nanocage to programmed death-ligand 1 (PD-L1) and programmed death-ligand 2 (PD-L2) expressed cancer cells is increased as compared with a nanocage not decorated with a programmed cell death protein 1 on the surface, and wherein the programmed cell death protein 1 comprises the amino acid sequence that is at least 70% identical to the amino acid sequence of SEQ ID NO: 1” recited in instant claim 16; and the limitations of instant claims 33 and 35.
However, Lázár-Molnár et al, throughout the literature, teach programmed cell death-1 (PD-1) is an inhibitory immune receptor, which plays critical roles in T cell co-inhibition and exhaustion, and is a prominent target for cancer immunotherapy; and a method of treating lung carcinoma in mice, wherein the method comprises administering to the mice having lung carcinoma a pharmaceutical composition comprising a fusion protein, and wherein the fusion protein comprises a high-affinity mutant PD-1 (HA PD-1), for example, Abstract; page 30, the 1st paragraph in Section “1. Introduction”; page 31, right column, the 2nd paragraph; pages 32-33, Sections 2.9-2.13; and pages 39-40, Figures 4-6. Lázár-Molnár et al further teach that one significant advantage of PD-1 mediated immunotherapy is the reduced rate of undesirable side effects observed in clinical trials, which is likely due to the primary involvement of PD-1 in the regulation of peripheral effector responses within inflamed tissues and the tumor microenvironment, for example, page 42, right column, the 2nd paragraph. Lázár-Molnár et al also teach PD-L1 and PD-L2 are ligands of PD-1, and mouse PD1 binds to the ligands of both mouse and human PD1, for example, Abstract; and page 31, the paragraph bridging the left and right columns. And as evidenced by the programmed cell death 1 [Mus musculus] document, mouse PD1 comprises an amino acid sequence of instant SEQ ID NO: 1 (see the amino acid sequence on page 3) and comprises the amino acids 8-128 of instant SEQ ID NO: 1 (at least 70% identical to the amino acid sequence of instant SEQ ID NO: 1), as shown below with Query being instant SEQ ID NO: 1 and Sbjct being mouse PD1:
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Therefore, it would have been obvious to one of ordinary skilled in the art to combine the teachings of Nam et al and Lázár-Molnár et al to develop a method of treating cancer, such as colon cancer and/or lung carcinoma, in mice, wherein the method comprises intratumorally administering to the mice having cancer a pharmaceutical composition comprising nanocages formed by self-assembly of a fusion protein comprising mouse PD1 linked to the C-terminus of a ferritin heavy chain protein (as a self-assembling protein) via a linker consisting of the amino acid sequence GSSGGSGSSGGSGGGDEADGSRGSQKAGVDE (identical to the linker of instant SEQ ID NO: 14), wherein the nanocage is decorated with mouse PD1 on its surface, wherein the mouse PD1 comprise the amino acid sequence that is at least 70% identical to the amino acid sequence of instant SEQ ID NO: 1, and wherein an immunogenic cell death inducer, such as a cyclophosphamide anticancer agent (a nitrogen mustard-based drug), is loaded in the nanocages.
Furthermore, with regards to the limitations “wherein the nanocages induce anti-tumor immunity activation at two immune checkpoints of an effector phase and a cognitive phase, wherein the anti-tumor immunity activation at the effector phase occurs in the tumor microenvironment (TME), and wherein the anti-tumor immunity activation at the cognitive phase occurs in the tumor-draining lymph node (TDLN)” and “wherein a binding ability of the nanocage to programmed death-ligand 1 (PD-L1) and programmed death-ligand 2 (PD-L2) expressed cancer cells is increased as compared with a nanocage not decorated with a programmed cell death protein 1 on the surface” recited in instant claim 16, first, these are result-oriented limitations. In the instant case, the method developed from the combined teachings of Nam et al and Lázár-Molnár et al comprises the same active method step, i.e., the same patient population, the same composition and the same route of administration, therefore, administering the same composition to the same patient population via the same route of administration would lead to the same effect, i.e., inducing anti-tumor immunity activation at two immune checkpoints of an effector phase and a cognitive phase, wherein the anti-tumor immunity activation at the effector phase occurs in the tumor microenvironment (TME), wherein the anti-tumor immunity activation at the cognitive phase occurs in the tumor-draining lymph node (TDLN), and wherein a binding affinity of the nanocage to PD-L1 and PD-L2 expressed cancer cells is increased as compared with a nanocage not decorated with a programmed cell death protein 1 on the surface. Therefore, the method developed from the combined teachings of Nam et al and Lázár-Molnár et al induces anti-tumor immunity activation at two immune checkpoints of an effector phase and a cognitive phase, wherein the anti-tumor immunity activation at the effector phase occurs in the tumor microenvironment (TME), wherein the anti-tumor immunity activation at the cognitive phase occurs in the tumor-draining lymph node (TDLN), and wherein a binding affinity of the nanocage to PD-L1 and PD-L2 expressed cancer cells is increased as compared with a nanocage not decorated with a programmed cell death protein 1 on the surface. Second, as stated above, Lázár-Molnár et al explicitly teach PD-L1 and PD-L2 are ligands of PD-1, and mouse PD1 binds to the ligands of both mouse and human PD1. Therefore, one of ordinary skilled in the art would understand and reasonably expect that for the nanocage used in the method developed from the combined teachings of Nam et al and Lázár-Molnár et al above, the binding affinity of such nanocage to PD-L1 and PD-L2 expressed cancer cells is increased as compared with a nanocage not decorated with a programmed cell death protein 1 on the surface. Third, since the nanocages in the method developed from the combined teachings of Nam et al and Lázár-Molnár et al above meet all the limitations of the nanocages recited in instant claim 16, the nanocages in the method developed from the combined teachings of Nam et al and Lázár-Molnár et al above would inherently have the same properties and functionality of the nanocages recited in instant claim 16. Therefore the nanocages in the method developed from the combined teachings of Nam et al and Lázár-Molnár et al above induce anti-tumor immunity activation at two immune checkpoints of an effector phase and a cognitive phase, wherein the anti-tumor immunity activation at the effector phase occurs in the tumor microenvironment (TME), wherein the anti-tumor immunity activation at the cognitive phase occurs in the tumor-draining lymph node (TDLN), and wherein a binding affinity of the nanocage to PD-L1 and PD-L2 expressed cancer cells is increased as compared with a nanocage not decorated with a programmed cell death protein 1 on the surface. And the MPEP states “Where the claimed and prior art products are identical or substantially identical in structure or composition, or are produced by identical or substantially identical processes, a prima facie case of either anticipation or obviousness has been established. In re Best, 562 F.2d 1252, 1255, 195 USPQ 430, 433 (CCPA 1977). "When the PTO shows a sound basis for believing that the products of the applicant and the prior art are the same, the applicant has the burden of showing that they are not." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). Therefore, the prima facie case can be rebutted by evidence showing that the prior art products do not necessarily possess the characteristics of the claimed product. In re Best, 562 F.2d at 1255, 195 USPQ at 433. See also Titanium Metals Corp. v. Banner, 778 F.2d 775, 227 USPQ 773 (Fed. Cir. 1985) (Claims were directed to a titanium alloy containing 0.2-0.4% Mo and 0.6-0.9% Ni having corrosion resistance. A Russian article disclosed a titanium alloy containing 0.25% Mo and 0.75% Ni but was silent as to corrosion resistance. The Federal Circuit held that the claim was anticipated because the percentages of Mo and Ni were squarely within the claimed ranges. The court went on to say that it was immaterial what properties the alloys had or who discovered the properties because the composition is the same and thus must necessarily exhibit the properties.).” (see MPEP § 2112.01 I). In addition, since the USPTO lacks the experimental facilities to make a further determination, the burden is on the Applicant to prove the otherwise.
One of ordinary skilled in the art would have been motivated to combine the teachings of Nam et al and Lázár-Molnár et al to develop a method of treating cancer, such as colon cancer and/or lung carcinoma, in mice, wherein the method comprises intratumorally administering to the mice having cancer a pharmaceutical composition comprising nanocages formed by self-assembly of a fusion protein comprising mouse PD1 linked to the C-terminus of a ferritin heavy chain protein (as a self-assembling protein) via a linker consisting of the amino acid sequence GSSGGSGSSGGSGGG DEADGSRGSQKAGVDE (identical to the linker of instant SEQ ID NO: 14), wherein the nanocage is decorated with mouse PD1 on its surface, wherein the mouse PD1 comprise the amino acid sequence that is at least 70% identical to the amino acid sequence of instant SEQ ID NO: 1, wherein an immunogenic cell death inducer, such as a cyclophosphamide anticancer agent (a nitrogen mustard-based drug), is loaded in the nanocages, wherein the nanocages induce anti-tumor immunity activation at two immune checkpoints of an effector phase and a cognitive phase, wherein the anti-tumor immunity activation at the effector phase occurs in the tumor microenvironment (TME), wherein the anti-tumor immunity activation at the cognitive phase occurs in the tumor-draining lymph node (TDLN), and wherein the binding affinity of such nanocage to PD-L1 and PD-L2 expressed cancer cells is increased as compared with a nanocage not decorated with a programmed cell death protein 1 on the surface, because Lázár-Molnár et al, throughout the literature, teach programmed cell death-1 (PD-1) is an inhibitory immune receptor, which plays critical roles in T cell co-inhibition and exhaustion, and is a prominent target for cancer immunotherapy; and a method of treating lung carcinoma in mice, wherein the method comprises administering to the mice having lung carcinoma a pharmaceutical composition comprising a fusion protein, and wherein the fusion protein comprises a high-affinity mutant PD-1 (HA PD-1). Lázár-Molnár et al further teach that one significant advantage of PD-1 mediated immunotherapy is the reduced rate of undesirable side effects observed in clinical trials, which is likely due to the primary involvement of PD-1 in the regulation of peripheral effector responses within inflamed tissues and the tumor microenvironment. Lázár-Molnár et al also teach PD-L1 and PD-L2 are ligands of PD-1, and mouse PD1 binds to the ligands of both mouse and human PD1. And as evidenced by the programmed cell death 1 [Mus musculus] document, mouse PD1 comprises an amino acid sequence of instant SEQ ID NO: 1 and comprises the amino acid sequence that is at least 70% identical to the amino acid sequence of instant SEQ ID NO: 1. And both Nam et al and Lázár-Molnár et al teach cancer immunotherapy.
A person of ordinary skilled in the art would have reasonable expectation of success in combining the teachings of Nam et al and Lázár-Molnár et al to develop a method of treating cancer, such as colon cancer and/or lung carcinoma, in mice, wherein the method comprises intratumorally administering to the mice having cancer a pharmaceutical composition comprising nanocages formed by self-assembly of a fusion protein comprising mouse PD1 linked to the C-terminus of a ferritin heavy chain protein (as a self-assembling protein) via a linker consisting of the amino acid sequence GSSGGSGSSGGSGGGDEADGSRGSQKAGVDE (identical to the linker of instant SEQ ID NO: 14), wherein the nanocage is decorated with mouse PD1 on its surface, wherein the mouse PD1 comprise the amino acid sequence that is at least 70% identical to the amino acid sequence of instant SEQ ID NO: 1, wherein an immunogenic cell death inducer, such as a cyclophosphamide anticancer agent (a nitrogen mustard-based drug), is loaded in the nanocages, wherein the nanocages induce anti-tumor immunity activation at two immune checkpoints of an effector phase and a cognitive phase, wherein the anti-tumor immunity activation at the effector phase occurs in the tumor microenvironment (TME), wherein the anti-tumor immunity activation at the cognitive phase occurs in the tumor-draining lymph node (TDLN), and wherein the binding affinity of such nanocage to PD-L1 and PD-L2 expressed cancer cells is increased as compared with a nanocage not decorated with a programmed cell death protein 1 on the surface.
Response to Applicant's Arguments
11. Applicant argues that the rejection fails to teach the newly added limitation “intratumorally administering”. Applicant further argues that “The dual targeting of the drug to both the TME and TDLN, resulting in immune activation, is not a mere result-oriented limitation. Rather, it is induced through intratumoral administration in addition to the unique configuration of the nanocage of the claimed invention, and achieves unexpected results that could not be predicted from the cited references.”
12. Applicant's arguments have been fully considered but have not been found persuasive.
In response to Applicant’s arguments about instant rejection:
First, the Examiner would like to point out that as stated in Section 10 above, in the instant case, the combined teachings of Nam et al and Lázár-Molnár et al teach a method of treating cancer, such as colon cancer and/or lung carcinoma, in mice, wherein the method comprises intratumorally administering to the mice having cancer a pharmaceutical composition comprising nanocages formed by self-assembly of a fusion protein comprising mouse PD1 linked to the C-terminus of a ferritin heavy chain protein (as a self-assembling protein) via a linker consisting of the amino acid sequence GSSGGSGSSGGSGGGDEADGSRGSQKAGVDE (identical to the linker of instant SEQ ID NO: 14), wherein the nanocage is decorated with mouse PD1 on its surface, wherein the mouse PD1 comprise the amino acid sequence that is at least 70% identical to the amino acid sequence of instant SEQ ID NO: 1, and wherein an immunogenic cell death inducer, such as a cyclophosphamide anticancer agent (a nitrogen mustard-based drug), is loaded in the nanocages.
Second, as stated in Section 10 above, with regards to the limitations “wherein the nanocages induce anti-tumor immunity activation at two immune checkpoints of an effector phase and a cognitive phase, wherein the anti-tumor immunity activation at the effector phase occurs in the tumor microenvironment (TME), and wherein the anti-tumor immunity activation at the cognitive phase occurs in the tumor-draining lymph node (TDLN)” and “wherein a binding ability of the nanocage to programmed death-ligand 1 (PD-L1) and programmed death-ligand 2 (PD-L2) expressed cancer cells is increased as compared with a nanocage not decorated with a programmed cell death protein 1 on the surface” recited in instant claim 16, first, these are result-oriented limitations. In the instant case, the method developed from the combined teachings of Nam et al and Lázár-Molnár et al comprises the same active method step, i.e., the same patient population, the same composition and the same route of administration, therefore, administering the same composition to the same patient population via the same route of administration would lead to the same effect, i.e., inducing anti-tumor immunity activation at two immune checkpoints of an effector phase and a cognitive phase, wherein the anti-tumor immunity activation at the effector phase occurs in the tumor microenvironment (TME), wherein the anti-tumor immunity activation at the cognitive phase occurs in the tumor-draining lymph node (TDLN), and wherein a binding affinity of the nanocage to PD-L1 and PD-L2 expressed cancer cells is increased as compared with a nanocage not decorated with a programmed cell death protein 1 on the surface. Therefore, the method developed from the combined teachings of Nam et al and Lázár-Molnár et al induces anti-tumor immunity activation at two immune checkpoints of an effector phase and a cognitive phase, wherein the anti-tumor immunity activation at the effector phase occurs in the tumor microenvironment (TME), wherein the anti-tumor immunity activation at the cognitive phase occurs in the tumor-draining lymph node (TDLN), and wherein a binding affinity of the nanocage to PD-L1 and PD-L2 expressed cancer cells is increased as compared with a nanocage not decorated with a programmed cell death protein 1 on the surface. Second, as stated above, Lázár-Molnár et al explicitly teach PD-L1 and PD-L2 are ligands of PD-1, and mouse PD1 binds to the ligands of both mouse and human PD1. Therefore, one of ordinary skilled in the art would understand and reasonably expect that for the nanocage used in the method developed from the combined teachings of Nam et al and Lázár-Molnár et al above, the binding affinity of such nanocage to PD-L1 and PD-L2 expressed cancer cells is increased as compared with a nanocage not decorated with a programmed cell death protein 1 on the surface. Third, since the nanocages in the method developed from the combined teachings of Nam et al and Lázár-Molnár et al above meet all the limitations of the nanocages recited in instant claim 16, the nanocages in the method developed from the combined teachings of Nam et al and Lázár-Molnár et al above would inherently have the same properties and functionality of the nanocages recited in instant claim 16. Therefore the nanocages in the method developed from the combined teachings of Nam et al and Lázár-Molnár et al above induce anti-tumor immunity activation at two immune checkpoints of an effector phase and a cognitive phase, wherein the anti-tumor immunity activation at the effector phase occurs in the tumor microenvironment (TME), wherein the anti-tumor immunity activation at the cognitive phase occurs in the tumor-draining lymph node (TDLN), and wherein a binding affinity of the nanocage to PD-L1 and PD-L2 expressed cancer cells is increased as compared with a nanocage not decorated with a programmed cell death protein 1 on the surface. And the MPEP states “Where the claimed and prior art products are identical or substantially identical in structure or composition, or are produced by identical or substantially identical processes, a prima facie case of either anticipation or obviousness has been established. In re Best, 562 F.2d 1252, 1255, 195 USPQ 430, 433 (CCPA 1977). "When the PTO shows a sound basis for believing that the products of the applicant and the prior art are the same, the applicant has the burden of showing that they are not." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). Therefore, the prima facie case can be rebutted by evidence showing that the prior art products do not necessarily possess the characteristics of the claimed product. In re Best, 562 F.2d at 1255, 195 USPQ at 433. See also Titanium Metals Corp. v. Banner, 778 F.2d 775, 227 USPQ 773 (Fed. Cir. 1985) (Claims were directed to a titanium alloy containing 0.2-0.4% Mo and 0.6-0.9% Ni having corrosion resistance. A Russian article disclosed a titanium alloy containing 0.25% Mo and 0.75% Ni but was silent as to corrosion resistance. The Federal Circuit held that the claim was anticipated because the percentages of Mo and Ni were squarely within the claimed ranges. The court went on to say that it was immaterial what properties the alloys had or who discovered the properties because the composition is the same and thus must necessarily exhibit the properties.).” (see MPEP § 2112.01 I). In addition, since the USPTO lacks the experimental facilities to make a further determination, the burden is on the Applicant to prove the otherwise. And in the instant case, other than statements/arguments, Applicant fails to provide any evidence to prove others.
Third, in the instant case, it appears to the Examiner that Applicant has identified latent properties of the instant claimed nanocages. And the MPEP states: “Mere recognition of latent properties in the prior art does not render nonobvious an otherwise known invention.” (see MPEP § 2145 II).
Fourth, with regards to Applicant’s arguments about unexpected results, the Examiner would like bring Applicant’s attention to MPEP § 716.02, which sets up the requirements and/or guidelines for 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))”; “Unexpected Results Commensurate in Scope With Claimed Invention [R-08.2012] 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)); and "The evidence relied upon should establish "that the differences in results are in fact unexpected and unobvious and of both statistical and practical significance." (see MPEP § 716.02(b)). And in the instant case, sPD-1 tested in instant Figures 3, 5, 7 and 8 is not disclosed in any of the cited prior art references.
Taken all these together, the method developed from the combined teachings of Nam et al and Lázár-Molnár et al meets each and every limitation recited in instant claims 16-19, 23 and 33-35. Therefore, the rejection is deemed proper and is hereby maintained.
Conclusion
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to LI N KOMATSU whose telephone number is (571)270-3534. The examiner can normally be reached Mon-Fri 8am-4pm EST.
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/LI N KOMATSU/Primary Examiner, Art Unit 1658
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