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 without traverse of Group I, claim 1-14, and 21-22 in the reply filed on 4/9/022 is acknowledged. The following species were also elected:
1-1) Immune check point molecule: PD-L1
1-2) Molecule configured to bind to said immune checkpoint molecule: PD1 (SEQ ID NO: 5)
2-1) Fusion site: C-terminus
2-2) Nature of relationship (i.e., stoichiometry): 24 ferritin monomers fused with the immune checkpoint molecule-binding molecule
3) Mutation: SEQ ID NO: 1 in which an amino acid of 81st and 83rd are substituted with alanine.
4) Type of cancer: Melanoma
5) Disease antigen epitope: gp100
Priority
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Information Disclosure Statement
The information disclosure statements (IDS) were submitted on 4/29/2022, 9/9/2022, 3/28/2023, 10/5/2023, and 11/27/2023 before the mailing of a first office action. The submissions are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Claim Status
Claims 1-2, 6-10, 12-14, and 21-22 are currently under examination. Claims 15-20 and 23-30 are withdrawn from examination. Claims 3-5 and 11 are canceled.
Specification
Previous Objections
The specification was previously objected to because of informalities located in paragraph [0165] of the specification. The recited text disclosed SEQ ID NOs did not match the SEQ ID NOs in Table 1.
Response to Arguments
Applicant’s arguments, see Applicant Reply, page 10, section I, filed 10/20/2025, with respect to the specification have been fully considered and are persuasive. The objection to the specification has been withdrawn.
Claim Interpretation
Previous Interpretation
The following is a quotation of 35 U.S.C. 112(f):
(f) Element in Claim for a Combination. – An element in a claim for a combination may be expressed as a means or step for performing a specified function without the recital of structure, material, or acts in support thereof, and such claim shall be construed to cover the corresponding structure, material, or acts described in the specification and equivalents thereof.
The following is a quotation of pre-AIA 35 U.S.C. 112, sixth paragraph:
An element in a claim for a combination may be expressed as a means or step for performing a specified function without the recital of structure, material, or acts in support thereof, and such claim shall be construed to cover the corresponding structure, material, or acts described in the specification and equivalents thereof.
The claims in this application are given their broadest reasonable interpretation using the plain meaning of the claim language in light of the specification as it would be understood by one of ordinary skill in the art. The broadest reasonable interpretation of a claim element (also commonly referred to as a claim limitation) is limited by the description in the specification when 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is invoked.
As explained in MPEP § 2181, subsection I, claim limitations that meet the following three-prong test will be interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph:
(A) the claim limitation uses the term “means” or “step” or a term used as a substitute for “means” that is a generic placeholder (also called a nonce term or a non-structural term having no specific structural meaning) for performing the claimed function;
(B) the term “means” or “step” or the generic placeholder is modified by functional language, typically, but not always linked by the transition word “for” (e.g., “means for”) or another linking word or phrase, such as “configured to” or “so that”; and
(C) the term “means” or “step” or the generic placeholder is not modified by sufficient structure, material, or acts for performing the claimed function.
Use of the word “means” (or “step”) in a claim with functional language creates a rebuttable presumption that the claim limitation is to be treated in accordance with 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph. The presumption that the claim limitation is interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is rebutted when the claim limitation recites sufficient structure, material, or acts to entirely perform the recited function.
Absence of the word “means” (or “step”) in a claim creates a rebuttable presumption that the claim limitation is not to be treated in accordance with 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph. The presumption that the claim limitation is not interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is rebutted when the claim limitation recites function without reciting sufficient structure, material or acts to entirely perform the recited function.
Claim limitations in this application that use the word “means” (or “step”) are being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, except as otherwise indicated in an Office action. Conversely, claim limitations in this application that do not use the word “means” (or “step”) are not being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, except as otherwise indicated in an Office action.
This application includes one or more claim limitations that do not use the word “means,” but are nonetheless being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, because the claim limitation(s) uses a generic placeholder that is coupled with functional language without reciting sufficient structure to perform the recited function and the generic placeholder is not preceded by a structural modifier. Such a claim limitation is: the generic placeholder is “molecule configured to” and the function is “bind to an immune checkpoint molecule.” in claim 1.
Because this/these claim limitation(s) is/are being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, it/they is/are being interpreted to cover the corresponding structure described in the specification as performing the claimed function, and equivalents thereof.
If applicant does not intend to have this/these limitation(s) interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, applicant may: (1) amend the claim limitation(s) to avoid it/them being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph (e.g., by reciting sufficient structure to perform the claimed function); or (2) present a sufficient showing that the claim limitation(s) recite(s) sufficient structure to perform the claimed function so as to avoid it/them being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph.
Response to Arguments
No argument was made in opposition to the invocation of 35 U.S.C. 112(f) in Applicant’s Reply, filed 10/20/2025. Consequently, claim 1 is interpreted under this statute. Based on the specification at Tables 1, 10, and 13, these molecules are interpreted to be peptides and polypeptides disclosed by these tables inserted at the locations designated by claim 1.
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.
Previous Rejections
Claims 1-14, and 21-22 were previously 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.
Response to Arguments
Applicant’s arguments, Applicant Reply, page 10, section IIB, filed 10/20/2025, with respect to the rejections of claims 1-2, 6-10, 12-14, and 21-22 under U.S.C. 112(a) have been fully considered and are persuasive. Therefore, the rejection has been withdrawn. The rejection of claims 3-4 and 11 have been rendered moot due to cancellation of said claims. However, upon further consideration, a new ground of rejection is made as described below.
New Rejections
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 1-2, 6-10, 12-14, and 21-22 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for the immune checkpoints Gp100, Ovalbumin, AH1, PD1, TPP1, PD-L1, SmPD1, RFP, TIGIT, CTLA4, LAG3, and TIM3, does not reasonably provide enablement for immune checkpoint inhibitors Her-2/neu, VISTA, 4-1BBL, Galectin-9, Adenosine A2a receptor, CD80, CD86, ICOS, ICOSL, BTLA, OX-40L, CD155, BCL2, MYC, PP2A, BRD1. BRD2, BRD3, BRD4, BRDT, CBP, E2F1, MDM2, MDMX, PPP2CA, PPM1D, STAT3, IDH1, PD-L2, BTLA, SLAMF7, 4-1BB, OX-40, ICOS, GITR, ICAM-1. BAFFR, HVEM, LFA-1, LIGHT, NKG2C, SLAMF7, NKp80, LAIR1, 2B4, CD2, CD3, CD 16, CD20, CD27, CD28, CD40L, CD48, CD52, EGFR family, AXL, CSF1R, DDR1, DDR2, EPH receptor family, FGFR family, VEGFR family, IGF1R, LTK, PDGFR family, RET, KIT, KRAS, NTRK1 and NTRK2. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
In order to determine compliance with the enablement requirement of 35 U.S.C. 112(a), the Federal Circuit developed a framework of factors in In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988), referred to as the Wands factors to assess whether any necessary experimentation required by the specification is "reasonable" or is "undue." Consistent with Amgen Inc. et al. v. Sanofi et al., 598 U.S. 594, 2023 USPQ2d 602 (2023), the Wands factors continue to provide a framework for assessing enablement in a utility application or patent, regardless of technology area. Guidelines for Assessing Enablement in Utility Applications and Patents in View of the Supreme Court Decision in Amgen Inc. et al. v. Sanofi et al., 89 FR 1563 (January 10, 2024). These factors include, but are not limited to:
(A) The breadth of the claims;
Claim 1 is broad as claimed because the sheer number of immune checkpoint molecules claimed. Some of these molecules include entire families.
(B) The nature of the invention;
The invention is a protein formed by self-assembly of 24 ferritin monomers, the protein having an outer surface on which a molecule configured to bind to an immune checkpoint molecule is fused to an N-terminus, a C-terminus or at least one of sites between adjacent a-helices of the ferritin monomer, including an A-B loop, B-C loop, C-D loop, or D-E loop, such that the ferritin protein is formed by self-assembly of 24 ferritin monomers.
(C) The state of the prior art;
These immune checkpoint molecules are known in the art, but each one has a separate pool of binding molecules. A few entries are families of molecules, each of which would potentially have their own binders.
For example, Kim et al. (Kim, et al. Cancer research 74.8: 2144-2151 (2014)) discloses STAT-3 binding molecules: “In summary, we screened and identified a specific STAT3-binding peptide (APTSTAT3) using aptide platform technology. With the addition of a cell-penetrating motif, the resulting APTSTAT3-9R aptide was able to suppress the viability and proliferation of cancer cells by blocking STAT3 phosphorylation, thereby inhibiting STAT3 downstream signaling.” (Kim et al., page 2149, col. 2, para. 2; page 2145, Figure 1).
For another example, Prochownik et al. (Prochownik, et al. Genes & cancer 1.6: 650-659. (2010)) discusses targeting MYC: “Improving the model by incorporating new and structurally diverse compounds as they become available will likely increase the rate at which more potent inhibitors are detected. Despite these shortcomings, there have been 2 dividends of this approach, particularly when considered in light of the random analog approach. The first is the simple demonstration that the overall pharmacophore model for identifying Myc compounds is viable and reasonably robust. The second is the surprising structural diversity of Myc inhibitors (Figure 2).”(Prochownik et al., page 654, col. 3, para. 2; page 655, Fig. 2).
This analysis can be repeated for each immune checkpoint molecule claimed for which no examples are provided.
(D) The level of one of ordinary skill;
A person of ordinary skill in the art would likely have at least a Master’s level education, and many would possess a Ph.D.
(E) The level of predictability in the art;
The predictability of protein-protein interactions is by default rather low. Access to large data sets of interactions can improve predictability through systems such as Alpha Fold.
Specifically for peptides, a single point mutation can change the biophysical properties of a peptide: “In summary, we have shown that the structural changes in the fibrillar state of the Aβ42 peptide that are observed to occur upon introduction of single point mutations can be accompanied by changes in the dominance of the microscopic processes by which these aggregates are themselves formed.” (Bolognesi et al. ACS Chem Bio 9:2 (2013) page 381 col. 2 para. 3) and “In summary, while ovispirin-1 and novispirin G-10 both had solution structures that were helical and amphipathic in the presence of TFE, a relatively simple change in their primary structure (a single glycine–isoleucine exchange) had profound effects on their respective toxicities for human erythrocytes and epithelial cells.” (Sawai et al. Protein Eng. 15:3 (2002) page 232 col. 1 para. 3).
Furthermore, many sequences allowed by the current scope of the claims, result in non-functional aggregates. Wang (Wang, et al. MAbs. Vol. 1. No. 3. Taylor & Francis, (2009)) discloses a variety of aggregation prone motifs that occur in commercial antibodies (Wang, page 262, Table 2). The scope of the claims currently may incorporate such motifs and result in non-functional aggregates.
(F) The amount of direction provided by the inventor and the existence of working examples;
Regarding claim 1, Applicants disclose working examples for Gp100, Ovalbumin, AH1, PD1, TPP1, PD-L1, SmPD1, RFP, TIGIT, CTLA4, LAG3, and TIM3. The data for these targets is thorough and enabling. However, the other recited targets differ in structure and function. When inserted between ferritin monomers in various locations, the wide range of the other claimed binding molecules will not necessarily still bind correctly. Consequently, a person of ordinary skill in the art would need to conduct undue experimentation to determine the best immune checkpoint binders for insertion into the ferritin monomers as well as determining the best location for said insertion. Claim 1 is rejected.
Regarding claim 2, claim 1 is rejected as described above. This claim does not provide any additional examples to resolve the enablement rejection of claim 1. Therefore, claim 2 is rejected.
Regarding claim 6, claim 1 is rejected as described above. This claim reduces the possible locations for insertion, but does not address the wide array of possible binding molecules to be tested to address the wide array of immune checkpoint molecules. Consequently, claim 6 is rejected.
Regarding claims 7-10, 12-14, and 21-22, claim 1 is rejected as described above. None of these claims provide any additional examples or reduce the number of immune checkpoint molecules claimed. Consequently, these claims do not remedy the issue of undue experimentation of claim 1 and are rejected.
Claim Rejections - 35 USC § 102
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 the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Previous Rejections
Claims 1, 2 ,4, and 12-13 were previously rejected under 35 U.S.C. 102(a)(1) as being anticipated by Nam et al. (WO2018012954, published 1/18/2018) as evidenced by Matlung et al. (Matlung et al., Immunol Rev. 276: 145–164 (2017).
Response to Arguments
Applicant’s arguments, page 14, section III, filed 10/20/2025, with respect to claims 1, 2, 4, and 12-13 have been fully considered and are persuasive. Claim 4 was canceled, rendering that rejection moot. The rejection of claims 1, 2, 4, and 12-13 has been withdrawn.
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.
Previous Rejections
Claims 1, 2, 4, and 11-13 were previously rejected under 35 U.S.C. 103 as being unpatentable over Nam et al. by Nam et al. (WO2018012954, published 1/18/2018) in view of Sunshine et al. Current Opinion in Pharmacology, 23, 32-38, (2015).
Response to Arguments
Applicant’s arguments, page 15, section IV, filed 10/20/2025, with respect to claims 1, 2, 4, and 11-13 have been fully considered and are persuasive. Claim 4 was canceled, rendering that rejection moot. The rejection of claims 1, 2, 4, and 11-13 has been withdrawn.
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 complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Previous Rejections
Claims 1-5 and 11-13 were provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1, 5, 6, 25 of copending Application No. 18/034,193 as evidenced by Sunshine et al. Current Opinion in Pharmacology, 23, 32-38, (2015) and Zhang et al. (Zhang et al. Chem. Int. Ed. 55, 16064 (2016)). Although the claims at issue are not identical, they are not patentably distinct from each other.
Response to Arguments
Applicant’s arguments, page 16, section V, filed 10/20/2025, with respect to the rejection of claims 1-5 and 11-13 under nonstatutory double patenting have been fully considered and are persuasive. Therefore, the rejection has been withdrawn. Claims 3-5 and 11 have been canceled, rendering those rejections moot. However, upon further consideration, a new ground of rejection is made as described below.
Claims 1-7, and 9-13 were provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-6, 9, 11-15 of copending Application No. 18/289,152 as evidenced by Zhang et al. (Zhang et al. Chem. Int. Ed. 55, 16064 (2016)). Although the claims at issue are not identical, they are not patentably distinct from each other.
Response to Arguments
Applicant’s arguments, page 16, section V, filed 10/20/2025, with respect to the rejection of claims 1-7 and 9-13 under nonstatutory double patenting have been fully considered and are persuasive. Therefore, the rejection has been withdrawn. Claims 3-5 and 11 have been canceled, rendering those rejections moot. However, upon further consideration, a new ground of rejection is made as described below.
New Rejections
Claims 1-2 and 12-13 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1, 5, 6, 25 of copending Application No. 18/034,193 as evidenced by Sunshine et al. Current Opinion in Pharmacology, 23, 32-38, (2015) and Zhang et al. (Zhang et al. Chem. Int. Ed. 55, 16064 (2016)). Although the claims at issue are not identical, they are not patentably distinct from each other.
Regarding claim 1, Applicant claim 1 recites A protein formed by self-assembly of 24_ferritin monomers, the protein having an outer surface on which a molecule configured to bind to an immune checkpoint molecule is fused to an N-terminus, a C-terminus or at least one of sites between adjacent a-helices of the ferritin monomer, including an A-B loop, B-C loop, C-D loop, or D-E loop, such that the ferritin protein is formed by self-assembly of 24 ferritin monomers, wherein the immune checkpoint molecule is any one selected from the group consisting of Her-2/neu, VISTA, 4-1BBL, Galectin-9, Adenosine A2a receptor, CD80, CD86, ICOS, ICOSL, BTLA, OX-40L, CD155, BCL2, MYC, PP2A, BRD1. BRD2, BRD3, BRD4, BRDT, CBP, E2F1, MDM2, MDMX, PPP2CA, PPM1D, STAT3, IDH1, PD1. CTLA4, PD-L1, PD-L2, LAG3, TIM3, TIGIT, BTLA, SLAMF7, 4-1BB, OX-40. ICOS, GITR, ICAM-1. BAFFR, HVEM, LFA-1, LIGHT, NKG2C, SLAMF7, NKp80, LAIR1, 2B4, CD2, CD3, CD 16, CD20, CD27, CD28, CD40L, CD48, CD52, EGFR family, AXL, CSF1R, DDR1, DDR2, EPH receptor family, FGFR family, VEGFR family, IGF1R, LTK, PDGFR family, RET, KIT, KRAS, NTRK1 and NTRK2.
‘193 claim 1 recites an antibody-like protein comprising self-assembly of a plurality of ferritin monomers, in which at least a CDR-ferritin fused with a complementarity determining region is included.
As shown by Sunshine, immune checkpoint molecules such as PD1 and PD-L1 may be targeted by antibodies (Sunshine, page 33, Table 1). Consequently, the CDR-ferritin fusions disclosed by ‘193 may be molecules configured to bind to an immune checkpoint molecule.
Claim 2 of ‘193 recites that: “the protein is a spherical protein formed by self-assembly of 24 ferritin monomers.” MPEP 2112.01(II) states: “A chemical composition and its properties are inseparable.” Zhang states: “All ferritins share the highly conserved architecture that comprises 24 subunits assembling into a spherical shell with octahedral symmetry.” (Zhang, page 16064, col. 2, para. 3). Consequently, the protein of claim 1 formed by self-assembly of ferritin monomers has 24 subunits has an inherent property that is inseparable from the sequence of ferritin. Therefore, claim 2 is anticipated by claim 1 of ‘193 and provisionally rejected.
Regarding the fusion locations, claim 6 of ‘193 discloses: “The antibody-like protein according to claim 1, wherein the complementarity determining region is fused to any one selected from the group consisting of the inside of a-helix, between adjacent a-helices, N-terminus, C-terminus, A-B loop, B-C loop, C-D loop, D-E loop, between N-terminus and A helix, and between E helix and C-terminus of the ferritin monomer.”
Applicant claim 1 also recites a Markush group that contains potential immune checkpoint molecules. Claim 25 of ‘193 discloses the antibody-like protein of claim 1, wherein the antibody is an antibody against one of a group of targets. Claim 25 of ‘193 recites all but 10 of the 60+ targets listed in Applicant claim 11.
Therefore, claims 1, 6, and 25 of ‘193 anticipate Applicant claim 1 as evidenced by Sunshine et al. and Zhang et al. and claim 1 is provisionally rejected.
Regarding claim 2, Applicant claim 1 is anticipated as described above. Claim 2 recites that: “the protein is a spherical protein.” MPEP 2112.01(II) states: “A chemical composition and its properties are inseparable.” Zhang states: “All ferritins share the highly conserved architecture that comprises 24 subunits assembling into a spherical shell with octahedral symmetry.” (Zhang, page 16064, col. 2, para. 3). Consequently, the protein of claim 1 formed by self-assembly of ferritin monomers has 24 subunits has an inherent property that is inseparable from the sequence of ferritin.
Therefore, claims 1, 6, and 25 of ‘193 anticipate Applicant claim 2 as evidenced by Sunshine et al. and Zhang et al. and claim 1 is provisionally rejected.
Regarding claim 12, Applicant claim 1 is anticipated as described above. Applicant claim 12 further recites that the molecule configured to bind to the immune checkpoint is a ligand or an antibody to the immune checkpoint molecule or a fragment thereof. Because claim 1 of ‘193 specifically describes using an antibody, claim 1 of ‘193 reads on this limitation and therefore Applicant claim 12 is anticipated by claims 1, 6, and 25 of ‘193.
Regarding claim 13, Applicant claim 1 is anticipated as described above. Applicant claim 13 further recites that the ferritin comprises a human ferritin heavy chain.
Claim 5 of ‘193 discloses: “The antibody-like protein according to claim 1, wherein the CDR-ferritin monomer is characterized in that the complementarity determining region is fused to a human ferritin heavy chain monomer.”
Consequently, claims 1, 5, 6, and 25 of ‘193 anticipates Applicant claim 13, and Applicant claim 13 is provisionally rejected.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1-2, 6-7, 9-10, and 12-13 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-6, 9, 11-15 of copending Application No. 18/289,152 as evidenced by Zhang et al. (Zhang et al. Chem. Int. Ed. 55, 16064 (2016)). Although the claims at issue are not identical, they are not patentably distinct from each other.
Regarding claim 1, Applicant claim 1 recites a protein formed by self-assembly of 24_ferritin monomers, the protein having an outer surface on which a molecule configured to bind to an immune checkpoint molecule is fused to an N-terminus, a C-terminus or at least one of sites between adjacent a-helices of the ferritin monomer, including an A-B loop, B-C loop, C-D loop, or D-E loop, such that the ferritin protein is formed by self-assembly of 24 ferritin monomers,wherein the immune checkpoint molecule is any one selected from the group consisting of Her-2/neu, VISTA, 4-1BBL, Galectin-9, Adenosine A2a receptor, CD80, CD86, ICOS, ICOSL, BTLA, OX-40L, CD155, BCL2, MYC, PP2A, BRD1. BRD2, BRD3, BRD4, BRDT, CBP, E2F1, MDM2, MDMX, PPP2CA, PPM1D, STAT3, IDH1, PD1. CTLA4, PD-L1, PD-L2, LAG3, TIM3, TIGIT, BTLA, SLAMF7, 4-1BB, OX-40. ICOS, GITR, ICAM-1. BAFFR, HVEM, LFA-1, LIGHT, NKG2C, SLAMF7, NKp80, LAIR1, 2B4, CD2, CD3, CD 16, CD20, CD27, CD28, CD40L, CD48, CD52, EGFR family, AXL, CSF1R, DDR1, DDR2, EPH receptor family, FGFR family, VEGFR family, IGF1R, LTK, PDGFR family, RET, KIT, KRAS, NTRK1 and NTRK2.
Claim 2 of ‘152 discloses: “The pharmaceutical composition according to claim 1, wherein the protein is a spherical protein formed by self-assembly of 24 ferritin monomers to which the molecule capable of binding to an immune checkpoint molecule is fused.
Claim 3 of ‘152 discloses: “The composition according to claim 1, wherein the molecule capable of binding to an immune checkpoint molecule is fused to at least one between adjacent a-helices of the ferritin monomer.”
p Claim 4 of ‘152 discloses: “The composition according to claim 1, wherein the molecule capable of binding to an immune checkpoint molecule is fused to N-terminus or C-terminus of the ferritin monomer.”
p Claim 5 of ‘152 discloses: “The composition according to claim 1, wherein the molecule capable of binding to an immune checkpoint molecule is fused to A-B loop, B-C loop, C-D loop or D-E loop of the ferritin monomer.”
Claim 13 of ‘152 discloses: “The pharmaceutical composition according to claim 1, wherein the immune checkpoint molecule is any one selected from the group consisting of Her-2/neu, VISTA, 4- 1BBL, Galectin-9, Adenosine A2a receptor, CD80, CD86, ICOS, ICOSL, BTLA, OX-40L, CD155, BCL2, MYC, PP2A, BRD1, BRD2, BRD3, BRD4, BRDT, CBP, E2F1, MDM2, MDMX, PPP2CA, PPM1D, STAT3, IDH1, PD1, CTLA4, PD-L1, PD-L2, LAG3, TIM3, TIGIT, 48 BTLA, SLAMF7, 4-1BB, OX -40, ICOS, GITR, ICAM-1, BAFFR, HVEM, LFA-1, LIGHT, NKG2C, SLAMF7, NKp80, LAIR1, 2B4, CD2, CD3, CD16, CD20, CD27, CD28, CD40L, CD48, CD52, EGFR family, AXL, CSF1R, DDR1, DDR2, EPH receptor family, FGFR family, VEGFR family, IGF1R, LTK, PDGFR family, RET, KIT, KRAS, NTRK1 and NTRK2.”
Consequently, claim 1 is anticipated by claims 2-5 and 13 of the ‘152 application and rejected.
Regarding claim 2, claim 1 is anticipated as described above. Claim 2 further recites the case wherein the protein is spherical. Claim 2 of ‘152 discloses: “The pharmaceutical composition according to claim 1, wherein the protein is a spherical protein formed by self-assembly of 24 ferritin monomers to which the molecule capable of binding to an immune checkpoint molecule is fused.
Consequently, claim 2 is anticipated by claims 2-5 and 13 of the ‘152 application and rejected.
Regarding claim 6, Applicant claim 1 is anticipated as described above. Applicant claim 6 further recites that the molecule configured to bind to the immune checkpoint molecule is fused between the N-terminus and the A helix or the C-terminus and the E helix of the ferritin monomers.
Claim 6 of ‘152 discloses: “The composition according to claim 1, wherein the molecule capable of binding to an immune checkpoint molecule is fused between N- terminus and A helix or between E helix and C-terminus of the ferritin monomer.”
Consequently, claim 6 is anticipated by claims 2-6 and 13 of the ‘152 application and rejected.
Regarding claim 7, Applicant claim 1 is anticipated as described above. Applicant claim 7 recites the case wherein the protein is mutated to reduce binding force to a human transferrin receptor. ‘152 claim 9 recites: “The composition according to claim 1, wherein the protein is mutated so that a binding force to a human transferrin receptor is reduced.”
Consequently, claim 7 is anticipated by claims 2-5, 9, and 13 of the ‘152 application and rejected.
Regarding claim 9, Applicant claim 1 is anticipated as described above. Applicant claim 9 recites:” The protein according to claim 1, wherein a binding force (K) of the protein to a transferrin receptor satisfies the following Equation 1:
K <= 100nM [Equation 1]
in Equation 1,wherein K = [P][T]/[PT], wherein [P] represents a concentration of the protein in an equilibrium state of a binding reaction between the protein and the transferrin receptor, [T] represents a concentration of the transferrin receptor in the equilibrium state, and [PT] represents a concentration of a complex of the protein and the transferrin receptor in the equilibrium state.
Claim 11 of ‘152 discloses: “The pharmaceutical composition according to claim 1, wherein the binding force (K) to the transferrin receptor satisfies Equation 1 below:
[Equation 1]
K > 10 nM
wherein Equation 1, K is [P][T]/[PT], wherein [P] represents a concentration of ferritin protein in an equilibrium state of a binding reaction between the ferritin protein and the transferrin receptor, [T] represents a concentration of the transferrin receptor in the equilibrium state, and [PT] represents a concentration of a complex of the ferritin protein and the transferrin receptor in the equilibrium state.
The K values of these two claims overlap substantially over the range of 10nM-100nM. MPEP 2144.05(I) states: “In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990).
Therefore, Applicant claim 9 is obvious over claims 2-5, 9, and 13 of the ‘152 application and rejected.
Regarding claim 10, Applicant claim 9 is obvious as described above. Applicant claim 10 further recites that the transferrin receptor is a human transferrin receptor.
Claim 12 of ‘152 discloses: “The composition according to claim 10, wherein the transferrin receptor is a human transferrin receptor.”
Therefore, Applicant claim 10 is obvious over claims 2-5, 9, 12, and 13 of the ‘152 application and rejected.
Regarding claim 12, Applicant claim 1 is anticipated as described above. Applicant claim 12 further recites that the molecule configured to bind to the immune checkpoint is a ligand or an antibody to the immune checkpoint molecule or a fragment thereof.
Claim 14 of ‘152 discloses: “The composition according to claim 1, wherein the molecule capable of binding to an immune checkpoint molecule is a ligand or a fragment thereof, a receptor or a fragment thereof, an antibody or a fragment thereof including an antigen binding region (CDR), which have a binding force to the immune checkpoint molecule.”
Therefore, Applicant claim 12 is anticipated by claims 2-5, 13, and 14 of the ‘152 application and rejected.
Regarding claim 13, Applicant claim 1 is anticipated as described above. Applicant claim 13 further recites that the ferritin comprises a human ferritin heavy chain.
Claim 15 of ‘152 discloses: “The composition according to claim 1, wherein the ferritin is a human ferritin heavy chain.”
Therefore, Applicant claim 13 is anticipated by claims 2-5, 13, and 15 of the ‘152 application and rejected.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
No claim is allowed.
Claims 1-2, 6-10, 12-14, and 21-22 are rejected.
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/DAVID PAUL BOWLES/ Examiner, Art Unit 1654
/LIANKO G GARYU/ Supervisory Patent Examiner, Art Unit 1654