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 .
Claim status
Claims 13-15,19, 23, 25-35, 37 are cancelled.
Claims 1-12, 16-18,20-22,24, 36 are under examination.
Claim Rejections - 35 USC § 112a
Written Description
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 1-12, 16-18,20-22,24, 36 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 purpose of the written description requirement is to ‘ensure that the scope of the right to exclude, as set forth in the claims, does not overreach the scope of the inventor’s contribution to the field of art as described in the patent specification.” Ariad Pharm., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1353-54 (Fed. Cir. 2010) (en banc) (quoting Univ. of Rochester v. G.D. Searle & Co., 358 F.3d 916, 920 (Fed. Cir. 2004)). To satisfy the written description requirement, the specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention. Vas-Cath, Inc. v. Mahurkar, 935 F.2d 1555, 1562-63, 19 USPQ2d 1111 (Fed. Cir. 1991). See also MPEP 2163.04.
For a claim to a genus, a generic statement that defines a genus of substances by only their functional activity does not provide an adequate written description of the genus. Reagents of the University of California v. Eli Lilly, 43 USPQ2d 1398 (CAFC 1997).
To provide adequate written description and evidence of possession of a claimed genus, the specification must provide sufficient distinguishing identifying characteristics of the genus. The factors to be considered include a disclosure of a representative number of species to describe the complete structure of the claimed genus and/or disclosure of a complete or partial structure, physical and/or chemical properties, functional characteristics, structure/function correlation, and any combination thereof.
Scope of the invention
Instant application recite the genera, functional equivalents, sequences with 80% or 90% sequence identity to ITRs, and ‘various modifications’ to base sequences in claims 1, 22 and 24 as described below:
Regarding claim 1, embodiments 1-6 recite functional equivalents of; ITRs (embodiments 1 and 2), LTRs (embodiment 3 and 4), leader sequences (embodiments 5 and 6). Specification defines functional equivalents as ‘equivalents that can be used in place of ITRs, LTRs or leader sequences from a functional viewpoint’. However, the specification fails to identify the specific sequences or the segments of the sequences that are essential to perform the function of the various functional equivalents in any of the embodiments. Therefore the specification does not enable a person of ordinary skill in the art to use the invention.
Regarding Claim 22, this claim recites first ITR with 80% or 90% identity to SEQ ID NO: 5 (embodiments 1 and 2) and second ITR with 80% or 90% identity to SEQ ID NO:6 (embodiments 4 and 5). The broadest reasonable interpretation of the scope of this genus is all possible sequences of any length that comprise a sequence at least 80% or 90% identical to SEQ ID NOs: 5 and 6 . For example, in the instant application, SEQ ID NO:5 has 145 nucleotides, and 80% sequence identity encompasses at least any 29 mismatches in the sequences, and 90% sequence identity encompasses at least any 15 mismatches which may cause the claimed genus to encompass an exponential number of species. Same analysis applies to SEQ ID NO:6. Also, the specification fails to disclose a representative numbers/sequences of species within the claimed genera or to identify parts of the sequences that are essential to perform the function of the ITRs. Therefore, Applicant was not in possession of the claimed genera in embodiments 1-2, and 4-5.
Also, various modifications to SEQ ID NO: 5, and SEQ ID NO:6 recited in embodiments 3 and 6 of claim 2 may also result in an exponential number of species under those genera, thus failing to explicitly disclose the species in possession of the claimed invention.
Claim 24 recites functional equivalents of the first ITR with 80% or 90% identity to SEQ ID NO: 7 (embodiments 1 and 2) and functional equivalents of the second ITR with 80%or 90% identity to SEQ ID NO:8 (embodiments 4 and 5). SEQ ID NOs:7 and 8 have 141 nucleotides each, and 80% sequence identity encompasses at least any 29 mismatches in the sequences, and 90% sequence identity encompasses at least any 15 mismatches which may cause the claimed genera to encompass an exponential number of species. Also, the specification fails to disclose a representative numbers/sequences of species within the claimed genera or to disclose what portions of the sequences are essential to perform the function of the ITRs. Therefore, Applicant was not in possession of the claimed genera. Also, the various modifications to SEQ ID NO: 7, and SEQ ID NO:8 (embodiments 3 and 6) may also result in an exponential number of species under those genera, thus failing to explicitly disclose the species in possession of the claimed invention.
Structure/function Relationship
The recited functional equivalents of ITRs, LTRs or leader sequences do not have specific sequences set forth in the specification. Though the specification defines functional equivalents as ‘equivalents that can be used in place of ITRs, LTRs or leader sequences from a functional viewpoint’, their functional efficiency can vary depending on the specific sequences and may interfere with the protein yield produced by the vector containing them. Also, the ITRs or their functional equivalents (claims 22 and 24) with either 80% or 90% sequence identity or with various base modifications may have varying functional efficiencies interfering with the function of the vectors containing them.
Conclusion
Therefore, the examiner concludes there’s insufficient written description for the instantly claimed genera of functional equivalents, sequences with 80% or 90% sequence identity to ITRs, and ‘various modifications’ to base sequences in claims 1, 22 and 24. Specifically such varying sequence identities or base modifications may result in exponential number of sequences under those genera. However, specification fails to disclose a representative numbers/sequences of species within the claimed genera or to identify parts of the sequences that are essential to perform the function of each of the genera.
Therefore, there’s insufficient written description support for instant claims
Claim Rejections - 35 USC § 112b
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 6, 21,22 and 24 are 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 6 (1) and (2) recite that the physiologically active protein is bound to the c-terminus via a linker. However, it’s unclear if the said protein is bound to C-terminus of the light or the heavy chain. In embodiments (3) and (4) recite that the light/heavy chains of the anti-TfR- antibody is bound to the c-terminus. However, it’s unclear if the antibody is bound to C-terminus of the light or the heavy chain or the physiologically active protein via a second linker.
Claims 21,22 and 24 use the phrase ‘represented by’, numerous times to relate the various SEQ ID NOs. to respective nucleotide sequences. It’s not clear what the phrase ‘represented by’ means in the context of the claims, because it brings the ambiguity of if the sequences are identical or similar to the given SEQ ID Nos.
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 text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1-12, 16-18,20-22,24, 36 are rejected under 35 U.S.C. 103 as being unpatentable over Koshimura et al. WO2018038243A1, and Galina et al. WO2020235543A1.
Regarding claim 1 , Koshimura teaches a method of producing a fusion protein of an anti- TfR antibody and a lysosomal enzyme which is a physiologically active protein( abstract, claims 1-12). The fusion protein was produced by expressing a vector incorporating a gene encoding the recombinant fusion protein, i.e. a nucleotide molecule (description, page 3, lines 1-3 on the machine translation version).
Koshimura does not teach the binding activity of the anti-TfR antibody and a nucleic acid molecule encoding a fusion protein of an anti-transferrin receptor antibody and a physiologically active protein, flanked by ITR or functional equivalents. Bien-Ly, Nga, et al. "Transferrin receptor (TfR) trafficking determines brain uptake of TfR antibody affinity variants." Journal of Experimental Medicine 211.2 (2014): 233-244,
However, the binding activity is a specific characteristic to the antibody which is evidenced by the Bien-Ly et al. 2014 which teaches a bispecific antibodies against TfR, and β-amyloid cleaving enzyme-1 (BACE1) can traverse the blood-brain-barrier and may have potential therapeutic effects (abstract, page 233). Mouse-specific anti-TfR IC50 values (binding activity) of two anti-TfR variants are disclosed as IC50 = 18nM and IC50 = 588 nM respectively.
Also, the vectors comprising nucleic acid molecules flanked by ITRs were known in the art at the effective filing date of the invention. In particular Galina teaches the nucleotide molecules recited in the embodiments (1) and (2) of the claim 1. Galina discloses a nucleic acid molecule used for production of recombinant adeno associated virus (AAV) virions containing a nucleotide sequence with first AAV ITR or its functional equivalent, a base sequence for inserting a nucleotide sequence which encodes a foreign protein or a nucleotide sequence encoding a foreign protein downstream, followed by a second ITR sequence or its’ functional equivalent which teaches the embodiment 1 of claim 1.
Galina also teaches the presence of a E2A region (a gene expression regulatory site) of adenovirus or a functional equivalent downstream of the first ITR or its functional equivalent, a nucleotide sequence encoding a foreign protein, and a second ITR or a functional equivalent which teaches the embodiment 2 of claim 1 (abstract and claim 1 of Galina, page 1).
Therefore, it is obvious to a person of ordinary skill in the art before the effective filling date of the claimed invention to modify the methods of producing a fusion protein taught by Koshimura with teachings of Galina that teaches various embodiments of a nucleic acid molecule consisting two ITR sequences or their functional equivalents, and a nucleotide sequence which encodes a foreign protein in between the ITRs. One of ordinary skill in the art would have been motivated to combine the teachings of Koshimura, and Galina to produce a fusion protein consisting of anti-TfR antibody and a physiologically active protein by replacing the foreign protein nucleotide sequence in Galina with that of fusion protein taught by Kushimura to produce a fusion protein that may have the ability to traverse the blood brain barrier for various therapeutic applications. There would have been a reasonable expectation of success to combine the teachings of Koshimura, and Galina, because Koshimura teaches a method of producing a fusion protein consisting of anti-TfR antibody and the physiologically active protein, lysosomal enzyme, and Galina teaches a nucleotide molecule that can be adopted to generate the fusion protein or a more optimized version of it taught by Kushimura.
Regarding claim 2, Koshimura teaches a conjugate of a fusion protein comprised of TfR antibody consisting of light and heavy chains and a lysosomal enzyme ( a physiologically active protein) derived from a nucleotide sequence, wherein the lysosomal enzyme is bound to the C-terminal side or the N-terminal side of the heavy chain directly by a peptide bond which teaches the embodiments 1 and 2 of the claim 2. (claim 14, page 1).
Koshimura also teaches another embodiment of the fusion protein in which the human lysosomal enzyme is bound to the C-terminal side or N-terminal side of the light chain of the TfR antibody directly by a peptide bond which teaches the embodiments 3 and 4 of the claim 2 (claim 14, page 1). Regarding claim 3, Koshimura teaches a fusion protein comprised of TfR antibody consisting of light and heavy chains, and a lysosomal enzyme ( a physiologically active protein) derived from a nucleotide sequence, wherein the lysosomal enzyme is bound to the C-terminal side or the N-terminal side of the heavy chain of the antibody via a linker which teaches the embodiment 1 and 2 of the claim 3 (claim 14, page 1).
Koshimura also teaches another embodiment, wherein the human lysosomal enzyme is bound to the C-terminal side or N-terminal side of the light chain of the antibody via a linker which teaches the embodiment 3 and 4 of the claim 3 (claim 14, page 1).
Regarding claim 4, Koshimura teaches a linker sequence connecting the lysosomal enzyme to the TfR antibody consisting 1 to 50 amino acids (claim 15, page 1).
Regarding claim 5, Koshimura teaches a linker sequence connecting the lysosomal enzyme to the TfR antibody, wherein the linker sequence is one glycine, one serine, an amino acid sequence (Gly-Ser) or an amino acid sequence (Gly-Gly-Ser) (claim 18, page 2).
Regarding claim 6, Koshimura teaches a TfR-antibody which consists of one immunoglobulin light chain and a one immunoglobulin heavy chain, where the c-terminal side of the light chain is bound to the C-terminal side of the heavy chain via a linker (line 8-11, paragraph 2, page 6). The lysosomal enzyme (physiologically active protein) may be bound to the C- or the N- terminus of the light chain or the heavy chain (claim 14, page, 2). Thus, Koshimura teaches the embodiments 1 and 2 of the claim 6,
Regarding claim 7, Koshimura teaches a second linker sequence arranged between the light chain and the heavy chain of the TfR-antibody which is a peptide chain composed of 12 to 18 or 15 to 25 amino acid residues (line 29, paragraph 4, page 6) which are in the range of 1-50 amino acids.
Regarding claim 8, Koshimura teaches a second linker sequence arranged between the light chain and the heavy chain of the TfR-antibody, wherein the linker sequence is one glycine, one serine, an amino acid sequence (Gly-Ser) or an amino acid sequence (Gly-Gly-Ser) (line 31, paragraph 4, page 6).
Regarding claim 9, Koshimura teaches a second linker sequences arranged between the light chain and the heavy chain of the TfR-antibody is a peptide chain composed of 12 to 18 or 15 to 25 amino acid residues (line 29, paragraph 4, page 6) which are in the range of 8-50 amino acids.
Regarding claim 10, Koshimura teaches a second linker sequence arranged between the light chain and the heavy chain of the TfR-antibody, wherein the linker sequence is an amino acid sequence Gly-Ser, amino acid sequence Gly-Gly-Ser or an amino acid sequence Gly-Gly-Gly (line 30-31, paragraph 4, page 6).
Regarding claim 11, Koshimura teaches the use of an expression vector where an internal ribosomal binding site (IRES) is located downstream of a gene encoding a desired protein (description, paragraph 1, page 10). In one embodiment, the nucleotide sequence encoding the fusion protein consisting of the anti-TfR-antibody with heavy and light chains and lysosomal enzyme also consist of a base sequence encoding a conjugate in which the lysosomal enzyme (i.e. the physiologically active protein) binds to C-or N- terminus of the heavy chain (claim 14, page 1 which teaches the embodiments 1 and 2 of claim 11.
Koshimura also teaches the use of an expression vector where an internal ribosomal binding site (IRES) is located downstream of a gene encoding a desired protein in their invention (description, paragraph 1, page 10). In one embodiment, the nucleotide sequence encoding the fusion protein consisting of TfR-antibody (consist of heavy and light chains) and lysosomal enzyme (the gene of interest) also consist of a base sequence encoding a conjugate in which the lysosomal enzyme (i.e. the physiologically active protein) binds to C-or N- terminus of the light chain (claim 14, page 1 which teaches the embodiments 3 and 4 of claim 11.
Regarding claim 12, Koshimura teaches the use of an expression vector where an internal ribosomal binding site (IRES) is located downstream of a gene encoding a desired protein in their invention (description, paragraph 1, page 10). And in one embodiment, the nucleotide sequence encoding the fusion protein consisting of TfR-antibody (consisting of heavy and light chains) and lysosomal enzyme (the gene of interest) also consist of a base sequence encoding a conjugate in which the lysosomal enzyme (i.e. the physiologically active protein) binds to C-or N- terminus of the heavy chain via a linker (claim 14, page 1 which teaches the embodiments 1 and 2 of claim 11.
Koshimura also teaches the use of an expression vector where an internal ribosomal binding site (IRES) is located downstream of a gene encoding a desired protein in their invention (description, paragraph 1, page 10). And in one embodiment, the nucleotide sequence encoding the fusion protein consisting of TfR-antibody (consisting of heavy and light chains) and lysosomal enzyme (the gene of interest) also consist of a base sequence encoding a conjugate in which the lysosomal enzyme (i.e. the physiologically active protein) binds to C-or N- terminus of the light chain via a linker (claim 14, page 1 which teaches the embodiments 3 and 4 of claim 11 .
Regarding claim 16, Koshimura teaches that the TfR-antibody in their invention to have a fab region in one embodiment which is an antigen binding fragment (description, line 12, paragraph 2), which is encoded by a nucleic acid molecule.
Regarding claim 17, Koshimura teaches that the TfR-antibody in their invention to have a fab region in one embodiment (description, line 12, paragraph 2), which is encoded by a nucleic acid molecule.
Regarding claim 18, Koshimura teaches that the fusion protein consists of the TfR-antibody and a lysosomal enzyme which is a physiologically active protein (claim1, page 1).
Regarding claim 20, Galina teaches that the nucleic acid molecule used in the production of the fusion protein is recombinant AAV, and in one embodiment the vector contains AAV reverse end repeats or ITRs present at the both ends of the nucleotide molecule (description, lines 44-47, paragraph 8, page 7).
Regarding claim 21, Galina teaches the sequences of the first and the second ITRs in their invention, in one embodiment the first and the second ITR sequences given by SEQ ID NOs 9 and 10 (description, lines 36-37, paragraph 10, page 7) are identical to the first and second ITRs given by the SEQ ID NOs 5 and 6 in the instant application. The sequences of instant application and Galina were aligned using the NCBI Blast align tool to determine the sequence similarities.
Alignment of the SEQ ID NO 5 of the instant application, and the SEQ ID 9 of Galina showing 100% match between the two sequences is shown in the below figure.
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Alignment of the SEQ ID NO 6 of the instant application, and the SEQ ID 10 of Galina showing 100% match between the two sequences is shown in the below figure.
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Regarding claim 22, see above for claim 21 where Galina teaches ITRs that are 100% identical to the sequences set forth in SEQ ID NOs 5 and 6. Therefore Galina teaches sequences that are 80% identical to the sequences set forth in SEQ ID NOs: 5 and 6.
Galina also teaches that the two ITR sequences set forth SEQ ID 9 and 10 may be modified by substitution, deletion or addition of preferably from 1-10 nucleotides, as long as its’ function is intact which teaches the embodiments 3 and 6 of claim 22 of the instant application (description, lines 36-37, paragraph 10, page 7).
Regarding claim 24, Galina teaches the sequences of artificially constructed functional equivalents of the first and second ITRs in their invention, in one embodiment the functional equivalents of first and the second ITR sequences set forth SEQ ID NOs 11 and 12 (description, lines 48-50, paragraph 14, page 7 and lines 7-8, paragraph 2, page 8) are 100% identical to the first and second ITRs given by the SEQ ID NOs 7 and 8 in the instant application. The sequences of instant application and Galina were aligned using the NCBI Blast align tool to determine the sequence similarities.
Alignment of SEQ ID NO 7 of the instant application, and the SEQ ID 11 of Galina showing 100% match between the two sequences is shown in the below figure. Therefore, the functional equivalent of the first ITR given by SEQ ID 7, is taught by Galina with more than 80% and 90% sequence identity (groups 1 and 2 of claim 24).
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Alignment of the SEQ ID NO8 of the instant application, and the SEQ ID 12 of Galina showing 100% match between the two sequences is shown in the below figure. Therefore the functional equivalent of the second ITR given by SEQ ID 8, is taught by Galina with more than 80% and 90% sequence identity (groups 4 and 5 of claim 24).
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Galina also teaches that the two ITR sequences set forth SEQ ID 11 and 12 may be modified by substitution, deletion or addition of preferably from 1-10 nucleotides, as long as its function is intact which teaches the embodiments 3 and 6 of claim 24 (description, lines 7-10, paragraph 2, page 8).
Regarding claim 36, Galina teaches an adeno associated virus (AAV) virions comprising the nucleic acid molecule which encodes a fusion protein comprising anti-TfR-antibody and a human lysosomal enzyme. (abstract, claim1, page 1).
Hence, the claims invention as a whole was prima facie obvious.
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.
Claim 1-12, 16-18, 20-22, 24 , and 36 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-13, 16, 17, 19, 21, 27, 29, and 30 of copending application No. 18/271,839. Although the claims at issue are not identical, they are not patentably distinct from each other because of the reasons mentioned below.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Regarding instant claim 1, the limitation of the nucleic acid molecule encoding a fusion protein of an anti-transferrin receptor (anti-TfR) antibody and physiologically active protein are recited in claims 1, 2, 19 and 21 of the U.S. application No. 18/271,839.
Where claim 1 of 18/271,839 recites a nucleotide containing a sequence encoding a fusion protein of a ligand and a protein having physiological activity along with all the other limitations of the nucleotide sequences recited in the six different embodiments of the said nucleotide in claim 1 of the instant application. Claim 2 of 18/271,839 recites that nucleic acid molecule according to claim 1 is an antibody. Claim 19, recites that the nucleic acid molecule according to claims 2, has specific affinity for a protein present on the surfaces of vascular endothelial cells. Claim 21 recites that the protein encoded by the nucleic acid molecule present on the surfaces of the vascular endothelial cells is selected from a group of proteins that include transferrin receptor.
The limitation ‘binding activity’ of the fusion protein to the transferrin receptor is a specific characteristic of the antibody and also taught by Bien-ly (see 103 claim rejection for claim1).
The limitations of the nucleic acid sequences recited in embodiments 1-6 of claim 1 in the instant application are recited in sequences 1-6 of claim 1 in U.S. application No. 18/271,839.
Regarding instant claim 2, the limitations of how the physiologically active protein is bound to the antibody including the 4 embodiments of the said limitation are recited in claim 3 of U.S. application No. 18/271,839.
Regarding instant claim 3, the limitations of how the physiologically active protein is bound to the antibody via a linker, including the 4 groups of varying embodiments of the said limitation are recited in claim 4 of U.S. application No. 18/271,839.
Regarding instant claim 4, the limitation of the number of amino acids in the linker peptide sequence is recited in the claim 5 of U.S. application No. 18/271,839.
Regarding instant claim 5, the limitation of various embodiments of the liker peptide sequences are recited in claim 6 of U.S. application No. 18/271,839.
Regarding instant claim 6, the limitations of how the second linker is connected between the light chain and heavy chain, and the limitation of how a first linker or a linker is used to bind the antibody and the physiologically active protein recited in various embodiments in groups 1-4 are recited in claim 7 of U.S. application No. 18/271,839. Note that how the linker is connected in embodiments 1 and 2, and how the second linker is connected in embodiments 3 and 4 are not clearly recited in the instant claim 6 (see 112 b rejection).
Regarding instant claim 7, the limitation of the number of amino acids in the linker peptide (recited in claim 6) sequence is recited in the claim 8 of U.S. application No. 18/271,839..
Regarding instant claim 8, the limitation of various embodiments of the liker peptide sequences are recited in claim 9 of U.S. application No. 18/271,839.
Regarding instant claim 9, the limitation of the number of amino acids in the second linker peptide sequence is recited in the claim 10 of U.S. application No. 18/271,839.
Regarding instant claim 10, the limitation of various embodiments of the liker peptide sequences are recited in claim 11 of U.S. application No. 18/271,839.
Regarding instant claim 11, limitations of the nucleotide sequence, where in the nucleotide contains a sequence that encode varying embodiments of the fusion protein with regard to how the physiologically active protein is bound to the antibody portion of the fusion protein (i.e., C-or N- terminus of the heavy or the light chain), followed by a sequence encoding an internal ribosome binding site, downstream there of nucleotide sequence encoding light or the heavy chain of the antibody are recited in claim 12 of U.S. application No. 18/271,839.
Regarding instant claim 12, limitations of the nucleotide sequence, where in the nucleotide contains a sequence that encode varying embodiments of the fusion protein with regard to how the physiologically active protein is bound via a linker to the antibody portion of the fusion protein (i.e., C-or N- terminus of the heavy or the light chain), followed by a sequence encoding an internal ribosome binding site, downstream there of nucleotide sequence encoding the light or the heavy chain of the antibody are recited in claim 13 of U.S. application No. 18/271,839.
Regarding instant claim 16, the limitation that the antibody is an antigen-binding fragment is recited in claim 16 of U.S. Patent No. 18/271,839.
Regarding instant claim 17, the limitation that the antibody is Fab is recited in claim 17 of U.S. application No. 18/271,839.
Regarding instant claim 18, the limitations of the group of proteins from which the physiologically active protein is selected is recited in claim 27 of U.S. Patent No. 18/271,.839.
Regarding instant claim 20, the limitations of how the first and second ITRs are derived (i.e. from adeno-associated virus, adenovirus or mutants) are recited in claim 29 of U.S. application No. 18/271,839.
Regarding instant claim 21, the limitations that disclose the first and second ITR sequences are recited in claim 30 of U.S. application No. 18/271,839.
Regarding instant claim 22, the limitations that disclose the allowable sequence identity percentages, and the base sequence modifications for first and second ITR sequences are recited in claim 31 of U.S. application No. 18/271,839.
Regarding instant claim 24, the limitations that disclose the allowable sequence identity percentages, and the base sequence modifications for functional equivalents of first and second ITR sequences are recited in claim 33 of U.S. application No. 18/271,839.
Regarding instant claim 24, the limitations that disclose the viral virion comprising the nucleic acid molecule in claim 1 is recited in claim 44 of U.S. application No. 18/271,839.
Conclusion
No claim is allowed.
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/HASHANTHI KOMITIGE ABEYRATNE-PERERA/ Examiner, Art Unit 1632
/PETER PARAS JR/ Supervisory Patent Examiner, Art Unit 1632