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 .
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, 13 and 31 are currently under examination. Claims 3-5 and 11 are canceled. Claims 15-20 and 23-30 are currently withdrawn.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 4/27/2026. 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.
New Claim Objections
Claims 14, 21, and 22 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Claim Rejections - 35 USC § 112
Previous Rejections
Claims 1-2, 6-10, 12-14, and 21-22 were previously 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.
Response to Arguments
Applicant’s arguments, see Applicant Reply, page 9, section I, filed 4/27/2026, with respect to claims 1-2, 6-10, 12-14, and 21-22 have been fully considered and are persuasive. The rejection of claims 1-2, 6-10, 12-14, and 21-22 has been withdrawn.
Double Patenting
Previous Rejections
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, see page 11, section II, filed 4/27/2026, with respect to claims 1-7 and 9-13 have been fully considered and are persuasive. The rejection of claims 1-7 and 9-13 has been withdrawn.
Claims 1-2 and 12-13 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, see page 11, section II, filed 4/27/2026, with respect to claims 1-2 and 12-13 have been fully considered and are persuasive. The rejection of claims 1-2 and 12-13 has been withdrawn.
Claims 1-2, 6-7, 9-10, and 12-13 were previously rejected on the ground of non-statutory double patenting.
Response to Arguments
Applicant’s arguments, see page 11, section II, filed 4/27/2026, with respect to claims 1-2, 6-7, 9-10, and 12-13 have been fully considered and are persuasive. The double patenting rejections of claims 1-2, 6-7, 9-10, and 12-13 have been withdrawn.
New Double Patenting Rejection
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.
Claims 1, 2, 6, 7, 8, 9, 10, 12, 13, and 31 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 12-14 of copending Application No. 18/289,179 (reference application) in view of Zhang et al. (Zhang, et al. International journal of molecular sciences 12.8: 5406-5421(2011)). Although the claims at issue are not identical, they are not patentably distinct from each other.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
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 any one selected from the group consisting of Gp100, Ovalbumin, AH1, PD 1, TPP1, PD-L1, SmPD1, RFP, TIGIT, CTLA4, LAG3, and TIM3 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.”
Regarding ferritin monomers, claim 1 of the ‘179 application discloses: “A ferritin protein comprising a foreign peptide fused to an outer surface thereof, which wherein the ferritin protein is mutated so that a binding force to a human transferrin receptor is reduced, wherein the foreign peptide is a molecule capable of binding to an immune checkpoint molecule, wherein the immune checkpoint molecule is one or more selected from the group consisting of PD1, PD-L1, and TIGIT, wherein the foreign peptide is an antibody or a fragment thereof having binding affinity for the immune checkpoint molecule, wherein the mutated ferritin protein is characterized in that amino acid No. 15, 16, 23, 82, and 84 in the sequence of SEQ ID NO: 1 are each substituted with alanine, and wherein the foreign peptide is fused at one or more positions selected from the group consisting of the N-terminus of the ferritin monomer, between the N-terminus and an A-helix, between the A-helix and a B-helix (A-B loop), between the B-helix and a C-helix (B-C loop), between the C-helix and a D-helix (C-D loop), between the D-helix and an E-helix (D-E loop), between the E-helix and a C-terminus, the C-terminus, inside the A-helix, inside the B-helix, inside the C-helix, inside the D-helix, and inside the E-helix.
The ‘179 application does not disclose a self-assembly of 24 ferritin monomers.
However, Zhang discloses that ferritin monomers assemble in groups of 24 to form maxi-ferritins: “Maxi-ferritins are composed of twenty-four identical or homologous subunits (~20 kDa) that assemble into a large spherical cage (outer diameter ~120 Å) with a hollow cavity (inner diameter ~80 Å). Mammalian ferritins often consist of two types of similar subunits, heavy (H) and light (L) chain, with a molecular weight of ~21 and ~19 kDa respectively.” (Zhang et al., page 5407, para. 5).
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention that the ferritin protein of the ‘179 application would form the self-assembly of 24 ferritin monomers as disclosed by Zhang.
A person of ordinary skill in the art would be motivated to create this assembly to achieve the outer diameter disclosed by Zhang or the self-assembly event could happen spontaneously. A person of ordinary skill in the art would have a reasonable expectation of success because Zhang discloses that ferritin monomer form structures of 24 monomers.
Consequently, claim 1 is obvious over the ‘179 application over Zhang et al. and provisionally rejected.
Regarding claim 2, claim 1 is obvious as described above. Claim 2 further recites the case wherein the protein is a spherical protein.
Zhang discloses that the self-assembling protein forms a spherical shape: “Self-assembling protein systems form a variety of supramolecular structures with a wide diversity of biological functions or designed properties. These complexes include filaments [3–6], protein lattices [7,8] and symmetric cages [8–11]. Cage architectures have been observed through the self-assembly of viruses capsid [9,10,12], vault [13], heat shock [14–16], DNA binding [17–21] and ferritin proteins [22–24]. These roughly spherical and hollow structures often possess internal icosahedral, octahedral or tetrahedral symmetry which plays an essential role in controlling subunit association. Protein cages have been developed as platforms for nano-structured material synthesis [25], drug delivery [26], cell specific targeting [27] and catalysis [28,29].” (Zhang et al., page 5407, para. 2).
Consequently, claim 2 is obvious over the ‘179 application over Zhang et al. and provisionally rejected.
Regarding claim 6, claim 1 is obvious as described above. Claim 6 further recites the case wherein the molecule is fused between an N-terminus and an A helix of the ferritin monomers or between an E helix and a C-terminus of the ferritin monomers.
Claim 1 of the ‘179 application discloses: “…wherein the foreign peptide is fused at one or more positions selected from the group consisting of the N-terminus of the ferritin monomer, between the N-terminus and an A-helix, between the A-helix and a B-helix (A-B loop), between the B-helix and a C-helix (B-C loop), between the C-helix and a D-helix (C-D loop), between the D-helix and an E-helix (D-E loop), between the E-helix and a C-terminus, the C-terminus, inside the A-helix, inside the B-helix, inside the C-helix, inside the D-helix, and inside the E-helix.”
Consequently, claim 6 is obvious over the ‘179 application over Zhang et al. and provisionally rejected.
Regarding claim 7, claim 1 is obvious as described above. Claim 7 further recites the case wherein the protein is mutated to reduce a binding force to a human transferrin receptor.
Claim 1 of the ‘179 application discloses: “A ferritin protein comprising a foreign peptide fused to an outer surface thereof, which is mutated so that a binding force to a human transferrin receptor is reduced,…”
Consequently, claim 7 is obvious over the ‘179 application over Zhang et al. and provisionally rejected.
Regarding claim 8, claim 1 is obvious as described above. Claim 1 of the ‘179 patent discloses the case wherein the 15th amino acid is substituted to alanine. This reads on Applicant claim 8.
Consequently, claim 8 is obvious over the ‘179 application over Zhang et al. and provisionally rejected.
Regarding claim 9, claim 1 is obvious 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 K< 100 nM [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 12 of the ‘179 application discloses: “The ferritin protein according to claim 1, wherein the binding force (K) to the transferrin receptor satisfies Equation 1 below: [Equation K> 10 nM (in 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 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).”
Substantial overlap exists between K > 10 nM and K < 100 nM. 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 1575, 16 USPQ2d 1934 (Fed. Cir. 1990).”
Consequently, claim 9 is obvious over the ‘179 application over Zhang et al. and provisionally rejected.
Regarding claim 10, claim 9 is obvious as described above. Claim 13 of the ‘179 application discloses: “The ferritin protein according to claim 12, wherein the transferrin receptor is a human transferrin receptor.
Consequently, claim 10 is obvious over the ‘179 application over Zhang et al. and provisionally rejected.
Regarding claim 12, claim 1 is obvious as described above. Claim 12 further recites the case wherein the molecule is a ligand or an antibody, to any one selected from the group consisting of Gp 100, Ovalbumin, AH1, PD1, TPP1, PD-L1, SmPD1, RFP, TIGIT, CTLA4, LAG3, and TIM3,or a fragment thereof.
Claim 1 of the ‘179 application discloses: “…wherein the immune checkpoint molecule is one or more selected from the group consisting of PD1, PD-L1, and TIGIT…”
Consequently, claim 12 is obvious over the ‘179 application over Zhang et al. and provisionally rejected.
Regarding claim 13, claim 1 is obvious as described above. Claim 13 further recites the case wherein the ferritin monomers comprise a human ferritin heavy chain.
Claim 14 of the ‘179 application discloses: “The ferritin protein according to claim 1, wherein the ferritin is a human ferritin heavy chain.”
Consequently, claim 13 is obvious over the ‘179 application over Zhang et al. and provisionally rejected.
Regarding claim 31, claim 1 is obvious as described above. Claim 1 of the ‘179 application discloses PD-L1 as an immune checkpoint molecule with two other possibilities. MPEP 2143(I)(E) states: “"Obvious to try" – choosing from a finite number of identified, predictable solutions, with a reasonable expectation of success;”
A reasonable expectation of success exists because this application is directed to an identical molecule as described above and is also target immune checkpoints.
Consequently, claim 31 is obvious over the ‘179 application over Zhang et al. and provisionally rejected.
Free of the Prior Art
Claims 1, 2, 6, 7, 8, 9, 10, 12, 13, 14, 21, 22, and 31 are free of the prior art, but some of these are claims are subject to new non-statutory double patenting rejections. Because the withdrawn claims would be subject to additional rejections, these rejections cannot be dropped under MPEP 1490(VI)(D)(2)(a).
Claims 14, 21, and 22, are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Regarding the prior art, claim 1 was amended to incorporate fusion sites for the immune checkpoint molecules at sites on the ferritin monomers that are not taught or suggested by the prior art.
The closest available prior art is Nam et al. (WO2018012954, published 1/18/2018) which discloses a general form of the claimed invention:
“nanocage produced by self-assembly of a fusion-protein consisting of ferritin heavy chain protein and SIRPα, according to an embodiment of the present invention, and FIG. 1B is a schematic diagram illustrating a schematic form of an anti-cancer complex hybrid nanocage including a fusion-protein in which a single chain-based antibody targeting PD -1/PD-L1 SCF as an immune checkpoint inhibitor is bound to the fusion-protein and ferritin heavy chain proteins” (Nam et al., para [0014], [0102], Fig. 1B).
However, the fusion sites at the A-B loop, B-C loop, C-D loop, and D-E loop are not taught or suggested in the prior art. Consequently, the protein of claim 1 and all dependent claims are novel and nonobvious.
Regarding claim 14 of the non-statutory double patenting, the limitation of claim 14 is not found in the claims of the ‘179 application and cannot be made obvious through prior art, because the other publications that disclose this limitation are not prior art.
Regarding claim 21 of the non-statutory double patenting, the limitation of claim 14 is not found in the claims of the ‘179 application and cannot be made obvious through prior art, because the other publications that disclose this limitation are not prior art.
Regarding claim 22 of the non-statutory double patenting, claim 22 depends from clam 21 and therefore is nonobvious.
Conclusion
Claims 1, 2, 6, 7, 8, 9, 10, 12, 13, and 31 are rejected.
Claims 14, 21, and 22 are objected to.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to David Paul Bowles whose telephone number is (571)272-0919. The examiner can normally be reached Monday-Friday 8:30-5:00.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Lianko Garyu can be reached on (571) 270-7367. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/DAVID PAUL BOWLES/ Examiner, Art Unit 1654
/LIANKO G GARYU/ Supervisory Patent Examiner, Art Unit 1654
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