DETAILED ACTION
Status of claim rejections
The objections of record to the specification are withdrawn in view of Applicant’s submission of a substitute specification in the response filed 02/17/2026.
The objections to claim 9 are withdrawn in view of Applicant’s cancellation of the claim in the response filed 02/17/2026.
The rejections of the claims under 35 USC 112(a) are maintained in view of Applicant’s amendments/arguments in the response filed 02/17/2026.
The rejections of record under 35 U.S.C. 103 are withdrawn in view of Applicant’s arguments and amendments in the response filed 02/17/2025.
The double patenting rejections of record are maintained/modified in view of Applicant’s arguments and amendments in the response filed 02/17/2025.
This Action is FINAL, as necessitated by Applicant’s amendments.
New Claim Objections
Claim 39 objected to because of the following informalities: claim 39 recites “wherein the cell-penetrating peptide is selected from the group consisting of: penetratin, Tat-derived peptide, VP22, transportan, Pep- 1, Pep-7, FHV coat-35-49, oligoarginine (R9-R12), CCMV Gag-7-25, 5413-PV, VP22, BP16, DPV3, DPV6, FAH coat, protamine 1, human cJun, Engrailed-2, Islet-1, HoxA-13, TP10, Transportan 10, MPGa, MPG3,CADY, Pepfect6, Pepfectl4, Pepfectl5, NickFect, Hel, sC18, pVEC, ARF (1-22), YTA2, PAR1, F2Pal10, BprPp (1-30), hLF peptide (19-40), Buforin 2, Crotamine, Azurin p18, hCT peptide (18-32), 5413-PVrev, Kaposi's sarcoma fibroblast growth factor, Signal sequence of Ig light chain from Cailman crocodylus, integrin p3 fragment, Grb2- SH2 domain, HIV-1 gp41 (1-23), HBV translocation motif, sperm-egg fusion protein (89-111), human calcitonin (9-32), C1O5Y, K-FGF”. There is a conjunction missing at the end of the claim (an “and”) between “C1O5Y, K-FGF”. It is suggested to Applicant to amend the claim to include the word “and”.
Appropriate correction is required.
Maintained/Modified Claim Rejections - 35 USC § 112(a)
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, 9-10, 12, 29, 32-35, and 39-43 are 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.
The written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, reduction to drawings, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the inventor was in possession of the claimed genus. A "representative number of species" means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus. See AbbVie Deutschland GmbH & Co., KG v. Janssen Biotech, Inc., 759 F.3d 1285, 1300, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014). The issue is whether the skilled artisan would understand inventor to have invented, and been in possession of, the invention as claimed.
Claim interpretation: The independent claim (and thus the dependent claims) requires “a fusion polypeptide, which comprises a multimerization domain sequence, a cell-penetrating peptide, a pH-sensitive fusogenic peptide, and a protease recognition sequence: wherein the protease recognition sequence comprises a furin recognition sequence and a cathepsin L recognition sequence.” Claim 9 recites configurations of each component of the fusion protein. Claim 10 requires an optional peptide linker between the domains recited in claim 1. Claim 12 recites a multimer of the fusion polypeptide according to claim 1. Claim 29 requires a kit comprising, at least, the fusion protein of claim 1. Claim 32-35 and 39-43 further specifies species of the multimerization domains, cell-penetrating peptides, pH-sensitive fusogenic peptides, furin recognition sequence, cathepsin L recognition sequence, and protease recognition sequence.
The specification defines "multimerization domain" as “any polypeptide or protein capable of multimerizing (i.e., forming a biomolecular complex) several copies of the fusion polypeptide (see p. 3 of the specification), "pH-sensitive fusogenic peptide” as “a class of polypeptides that is capable of undergoing a conformational change under acidic conditions (e.g., pH<6.5), thereby promoting its fusion with an endocytic vesicle membrane (see p. 3), and "cell-penetrating peptide (CPP)" as “a polypeptide capable of promoting cellular uptake of various molecules” (see p. 4-5). As such, the claimed limitations required of the fusion protein are interpreted to include 1) any polypeptide or protein capable of multimerizing (i.e., forming a biomolecular complex) several copies of the fusion polypeptide, 2) any polypeptide that is capable of undergoing a conformational change under acidic conditions thereby promoting its fusion with an endocytic vesicle membrane, 3) polypeptide capable of promoting cellular uptake of various molecules, 4) any furin recognition sequence, and 5) any cathepsin L recognition sequence. As shown in the specification, the components of the fusion protein are defined by functional limitations. The question at issue is whether the skilled artisan would have understood Applicant to have been in possession of the massive genus of multimerization domains, fusogenic peptides, cell-penetrating peptides, and fusion proteins as encompassed by the instant claims.
Reduction to practice and disclosure of drawings or structural chemical formulas: Applicant discloses in the specification preparation of the TINNEL multimerization delivery system (see Table 1). Applicant utilized the nucleic acid sequences encoding TAT48-60 (SEQ ID NO: 14), INF7 (SEQ ID NO: 12), leucine zipper multimerization domain (SEQ ID NO: 1), cathepsin L recognition sequence (SEQ ID NO: 10), furin recognition sequence (SEQ ID NO: 8), and a cargo molecule (eGFP or GFP beta-1-10, ZFP9, Ppm1b (see Example 2, table 4-6).
Sufficient, relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure: Applicant has not provided information as to the defining structural characteristics that would lead one of ordinary skill in the art to the identity of the massive genus of polypeptides or protein capable of multimerizing (i.e., forming a biomolecular complex) several copies of the fusion polypeptide, 2) any polypeptide that is capable of undergoing a conformational change under acidic conditions thereby promoting its fusion with an endocytic vesicle membrane, 3) polypeptide capable of promoting cellular uptake of various molecules, 4) any furin recognition sequence, and 5) any cathepsin L recognition sequence in a fusion protein as encompassed by the claimed invention. Applicant’s claims encompass. Applicants have not disclosed which structures recited by the claims (other than the specific ones reduced to practice in the specification) would be necessary for the creation of the functional components capable for use in the fusion protein. Even with knowledge in the art regarding creation of fusion proteins, one of ordinary skill would not know what structural features are required for the outcome of creating a fusion protein that retains functional ability of forming a biomolecular complex of several copies of the fusion polypeptide, undergoing a conformational change under acidic conditions thereby promoting fusion with an endocytic vesicle membrane, promoting cellular uptake of various molecules, etc. without a recognized correlation between structure and function. This is not sufficient to meet the written description requirement. The specification does not provide adequate disclosure for fusion protein components with that much variation for the claimed purpose.
Lack of support for massive genus of multimerization domain sequences, cell-penetrating peptides, pH-sensitive fusogenic peptides, and protease recognition sequences: The specification fails to teach and/or provide support for possession of the multimerization domain sequences, cell-penetrating peptides, pH-sensitive fusogenic peptides, and protease recognition sequences, etc. as there is no correlation or defining characteristic that would convey the identity of these components with the ability to perform the functions as broadly claimed.
In support of the claimed genus, Applicant has only demonstrated possession of: the fusion proteins of SEQ ID NO: 16-18, containing SEQ ID NO: 14 (TAT48-60), 12 (INF7), 8 (furin), 10 (cathepsin L), 1 (multimerization domain). There is no support in the specification for the use of any polypeptide or protein capable of multimerizing several copies of the fusion polypeptide, any polypeptide that is capable of undergoing a conformational change under acidic conditions thereby promoting its fusion with an endocytic vesicle membrane, polypeptide capable of promoting cellular uptake of various molecules, any furin recognition sequence, and any cathepsin L recognition sequence. Thus, the data generated for the creation and use of the specific fusion proteins disclosed in the specification cannot reasonably be extrapolated to and applied to support possession of the entire claimed genus of possible fusion polypeptides, polypeptides capable of multimerizing several copies of the fusion polypeptide, polypeptides capable of undergoing a conformational change under acidic conditions thereby promoting its fusion with an endocytic vesicle membrane, polypeptides capable of promoting cellular uptake of various molecules, furin recognition sequences, and cathepsin L recognition sequences as claimed, because no one species, combination, or variant accounts for the variability amongst the claimed genus. As in Ariad, merely drawing a fence around the outer limits of a purported genus is not an adequate substitute for describing a variety of materials constituting the genus and showing that one has invented a genus and not just a species. “A patent is not a hunting license. It is not a reward for the search, but compensation for its successful conclusion.” Brenner v. Manson, 383 U.S. 519, 536 (1966).
The specification, then, is considered devoid of sufficiently detailed, relevant, identifying characteristics demonstrating that Applicant was in possession of the claimed genus of subject(s) in need thereof, i.e., additional complete or partial structures, other physical and/or chemical properties, functional characteristics coupled with a known or disclosed correlation between function and structure, or some combination thereof demonstrating possession of the claimed genus. Therefore, the claims are rejected under 35 U.S.C. 112(a) for lack of written description.
Response to Arguments
Applicant's arguments filed 02/17/2026 have been fully considered but they are not persuasive.
On pg. 10-15 of the remarks, Applicant argues Example 1 and the Li Declaration (given its fullest consideration) provide one of ordinary skill the capability to select specific sequences of CPPs, pH-sensitive peptides, furin sequences, cathepsin L, and multimerization domains. Applicant also points to Fig. 3-4 Section 4 of the declaration and Fig. 7 of the specification to that the selection of different multimerization domains all impart enhanced endocytosis efficiency to the delivery system. Applicant then points to Example 2 and Fig. 9-11 to show that incorporation of the peptide, CTSL and furin cleavage sites into the delivery system improved endocytisus efficiency, endosomal escape, and high serum tolerance. Applicant argues that the CTSL and furin cleavage sites added together into a delivery system provides superior performance and while CPP and fusogenic peptides are known in the art for intracellular delivery generally, the application discloses a representative number of species such that a PHOSITA can readily obtain CPPs other than Tat and other fusogenic peptides other than INF7 and would still reasonably expect a similar technical effect of the resulting fusion protein. Applicant argues the definition of multimerization domain, cathepsin L recognition sequence, and furin protease recognition sequence clearly defined and generally known in the art, the working example efficacy, sections 16-18, and 21-23 of the data in the Li declaration and urges that a PHOSITA can use the ample guidance in the application to select suitable CPPs, fusogenic peptides, multimerization domains, cathepsin L and furin protease sequences and reasonably expect it to function and have the properties disclosed.
In response, the examiner disagrees. As discussed above, the specification defines the components of the fusion protein by functional limitations. While the examiner appreciates the data provided in the declaration, Applicant has not provided information as to the defining structural characteristics that would lead one of ordinary skill in the art to the identity of the massive genus of polypeptides or protein capable of multimerizing (i.e., forming a biomolecular complex) several copies of the fusion polypeptide, 2) any polypeptide that is capable of undergoing a conformational change under acidic conditions thereby promoting its fusion with an endocytic vesicle membrane, 3) using any polypeptide capable of promoting cellular uptake of various molecules, 4) using any furin recognition sequence, and 5) any cathepsin L recognition sequence in a fusion protein which Applicant’s claims broadly encompass. Applicants have not disclosed which structures recited by the claims (other than the specific ones reduced to practice in the specification) would be necessary for the creation of the functional components capable for use in the fusion protein. The specification does not provide adequate disclosure for fusion protein components with that much variation for the claimed purpose. The invention being claimed must be sufficiently concrete so that it can be describe sufficiently to set it apart from what came before it. The invention must be described with enough clarity such that it is assured that the inventor actually has possession and knowledge of the nique composition that makes it worthy of patent protection. Disclosing the specific results of the combined structures that were actually reduced to practice cannot be reasonably extrapolated to include a massive genus of a combination of fusion protein components for the same desired results (i.e., improved endocytosis efficiency, endosomal escape, and high serum tolerance). The various components as set forth broadly in the instant claims are not adequate to support the assertion that Applicant was indeed in possession of the invention at the time of filing. Thus, the rejection is maintained as set forth above.
New Claim Rejections - 35 USC § 112(b)
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claim 39 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 39 recites “wherein the cell-penetrating peptide is selected from the group consisting of: penetratin, Tat-derived peptide, VP22, transportan, Pep- 1, Pep-7, FHV coat-35-49, oligoarginine (R9-R12), CCMV Gag-7-25, 5413-PV, VP22, BP16, DPV3, DPV6, FAH coat, protamine 1, human cJun, Engrailed-2, Islet-1, HoxA-13, TP10, Transportan 10, MPGa, MPG3,CADY, Pepfect6, Pepfectl4, Pepfectl5, NickFect, Hel, sC18, pVEC, ARF (1-22), YTA2, PAR1, F2Pal10, BprPp (1-30), hLF peptide (19-40), Buforin 2, Crotamine, Azurin p18, hCT peptide (18-32), 5413-PVrev, Kaposi's sarcoma fibroblast growth factor, Signal sequence of Ig light chain from Cailman crocodylus, integrin p3 fragment, Grb2- SH2 domain, HIV-1 gp41 (1-23), HBV translocation motif, sperm-egg fusion protein (89-111), human calcitonin (9-32), C1O5Y, K-FGF”. The use of parentheses renders the claims indefinite because it is unclear whether thelimitations within the parentheses are part of the claimed invention, or what the numbers in the parentheses represent (e.g., is BprPp (1-30) the number of amino acids in the BprPp peptide?). It is suggested that the parentheses around the species be removed and/or an explanation of what the species in the parentheses represent.
New Claim Rejections - 35 USC § 112(d)
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 34 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 34 recites “wherein the furin recognition sequence comprises R-X1-X2-R (SEQ ID NO: 47) or R- R-X1-X2-R (SEQ ID NO: 48), wherein X1 is any amino acid, and X2 is K or R; or comprises the sequence shown in SEQ ID NO: 49 or SEQ ID NO: 8”. However, claim 1 (from which this claim depends) recites “wherein the furin recognition sequence comprises R-X1-X2-R (SEQ ID NO: 47), wherein X1 is any amino acid and X2 is K or R”. The limitations of claim 34 improperly broadens the scope of furin recognition sequence required by claim 1. A claim in dependent form must contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Response to Arguments
Applicant’s arguments, see pg. 16-22, and Applicant’s Declaration filed 02/17/2026 with respect to the rejections of the claims under 35 USC 103 have been fully considered and are persuasive. The rejections of record have been withdrawn.
Modified 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.
Claims 1, 10-12, 29, 32-35, and 39-43 provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1, 9, 25, 29-31, 37-41 of copending Application No. 17/626351 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other for the reasons set forth below. The claims of the copending application are listed below, with overlapping limitations at issue in bold.
1. A fusion protein, which comprises from N-terminus to C-terminus a cell-penetrating peptide, a pH-sensitive fusogenic peptide and a protease recognition sequence, wherein the protease recognition sequence comprises a furin recognition sequence and a cathepsin L recognition sequence, and wherein the furin recognition sequence comprises R-X1- X2-R (SEQ ID NO: 1), wherein X1 is any amino acid, and X2 is K or R.
9. The fusion protein according to claim 1, wherein the fusion protein further comprises a specific binding sequence, the specific binding sequence allows another molecule to specifically bind thereto.
25. A kit comprising one or more of (i)-(iv) and an instruction for transfection and/or intracellular delivery:
(i) the fusion protein according to claim 1, wherein the fusion protein optionally comprises a specific binding sequence allowing another molecule to specifically bind thereto;
(ii) a complex comprising the fusion protein as defined in (i) and a cargo molecule;
(iii) a composition comprising the fusion protein as defined in (i) and a cargo molecule;
(iv) an isolated nucleic acid molecule comprising a nucleotide sequence encoding the fusion protein as defined in (i), the complex as defined in (ii), or the composition as defined in (iii);
(v) a vector comprising the isolated nucleic acid molecule as defined in (iv); or,
(vi) a host cell comprising the isolated nucleic acid molecule as defined in (iv) or the vector as defined in (v).
29. The fusion protein according to claim 1, characterized by one or more of the following:
(i) the furin recognition sequence comprises R-R- Xi-X2-R (SEQ ID NO: 2), wherein Xi is any amino acid, and X2 is K or R; a sequence shown in SEQ ID NO: 3; or a sequence shown in SEQ ID NO: 4;
(ii) the cathepsin L recognition sequence comprises a sequence shown in SEQ ID NO: 6;
(iii) the pH-sensitive fusogenic peptide comprises INF7 or comprises a sequence shown in SEQ ID NO: 8;
(iv) the cell-penetrating peptide comprises Tat(48-60) or comprises a sequence shown in SEQ ID NO: 10.
30. The fusion protein according to claim 1, wherein the protease recognition sequence comprises SEQ ID NO: 3 and SEQ ID NO: 6; or the protease recognition sequence comprises SEQ ID NO: 4 and SEQ ID NO:6.
31. The fusion protein according to claim 9, further comprising characterized by one or more of the following: (i) the specific binding sequence comprises a leucine zipper peptide (i.e., a multimerization domain as instantly claimed).
37. The fusion protein according to claim 1, wherein the cell-penetrating peptide is selected from the group consisting of penetratin, Tat-derived peptide, VP22, transportan, Pep-1, Pep-7, FHV coat-35-49, oligoarginine (R9-R12), CCMV Gag-7-25, 5413-PV, VP22, BP16, DPV3, DPV6, FAH coat, protamine 1, human cJun, Engrailed-2, Islet-1, HoxA-13, TP10, Transportan 10, MPGa, MPG3, CADY, Pepfect6, Pepfectl4, Pepfectl5, NickFect, Hel, sC18, pVEC, ARF (1-22), YTA2, PAR1, F2Pal10, BprPp (1-30), hLF peptide (19-40), Buforin 2, Crotamine, Azurin p18, hCT peptide (18-32), 5413-PVrev, Kaposi's sarcoma fibroblast growth factor, Signal sequence of Ig light chain from Caiiman crocodylus, integrin (33 fragment, Grb2- SH2 domain, HIV-1 gp41 (1-23), HBV translocation motif, sperm-egg fusion protein (89-111), human calcitonin (9-32), C105Y, and K-FGF.
38. The fusion protein according to claim 1, wherein the pH-sensitive fusogenic peptide is selected from the group consisting of INF7 (SEQ ID NO: 8), HA2 (SEQ ID NO: 38), KALA (SEQ ID NO: 39), GALA (SEQ ID NO: 40) and melittin (SEQ ID NO: 41).
39. (New) The fusion protein according to claim 1, wherein the cathepsin L recognition sequence comprises a sequence shown in SEQ ID NO: 6 (i.e., the same sequence as instant SEQ ID NO 10).
40. (New) The fusion protein according to claim 1, wherein the pH-sensitive fusogenic peptide comprises a sequence shown in SEQ ID NO: 8 (i.e., the same sequence as instant SEQ ID NO 12).
41. (New) The fusion protein according to claim 1, wherein the cell-penetrating peptide comprises a sequence shown in SEQ ID NO: 10 (i.e., the same sequence as instant SEQ ID NO 14).
As it relates to the instantly claimed invention, it is clear that the patent claims are an obvious variant of the instantly claimed invention.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Response to Arguments
On pg. 22 of the remarks, Applicant requests that the provisional rejection be held in abeyance until allowable subject matter can be determined.
In response, the rejections are maintained because both copending applications are, as discussed above, obvious variants of the claimed invention, as set forth above. Please note that only objections or requirements as to form not necessary for further consideration of the claims may be held in abeyance until allowable subject matter is indicated. Therefore, an application must not be allowed unless the required compliant terminal disclaimer is filed and/or the withdrawal of the nonstatutory double patenting rejection is made of record by the examiner (see MPEP § 804.02 (IV) for filing terminal disclaimers required to overcome nonstatutory double patenting rejections in applications filed on or after June 8, 1995).
Examiner’s Note
The examiner notes that the rejections of record of the claims in view of Wadia, Wiley, Bosch, Lin, Chappell, and Divita have been withdrawn because the prior art does not teach or suggest the fusion protein component arrangement from N-terminus to C-terminus with such specificity as to render the claims non-novel and unobvious. SinoBiological (2007-2025 Fusion Proteins Overview https://www.sinobiological.com/resource/protein-review/fusion-protein; pages 1-15) evidences the that the order of a fusion protein is critical because it affects a protein’s function, expression level, and folding. The closest prior art was previously cited in the withdrawn 35 USC 103 rejection.
Conclusion
NO CLAIMS ALLOWED.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any 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.
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure:
Massodi I, Bidwell GL 3rd, Raucher D. Evaluation of cell penetrating peptides fused to elastin-like polypeptide for drug delivery. J Control Release. 2005 Nov 28;108(2-3):396-408.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to GEORGIANA C REGLAS whose telephone number is (571)270-0995. The examiner can normally be reached M-Th: 8:00am-2:00pm.
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/G.C.R./Examiner, Art Unit 1651
/THOMAS J. VISONE/Supervisory Patent Examiner, Art Unit 1672