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 .
Detailed Action
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 Examiner for this Application has changed. Please direct all future correspondence to SPE Maria Leavitt, AU 1634. Additional contact information can be found at the end of this paper.
This action is in response to the papers filed on August 4, 2025. Claims 19-39 are currently pending. Claims 19, 23 24, 28, 29, 32-37 have been amended by Applicants’ amendment filed on 08/04/2025. No claims were canceled or newly added.
Applicant's election with traverse of Group I; and species elections (a) SEQ ID NO: 7 from dependent claim 23 as the signal peptide, and (b) SEQ ID NO: 12 from dependent claim 25 as the FGF fusion protein in the reply filed on 2025-03-18 was previously acknowledged. The restriction requirement was previously made FINAL.
Claims 38-39 were previously withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim.
Therefore, claims 19-37 are currently under examination to which the following grounds of rejection are applicable.
Priority
The present application is a 371 of PCT/EP2020/061015 filed April 20, 2020. Which claims benefit of EPO 19305518.3 filed April 19, 2019 and EPO 19305768.4 filed on June 17, 2019. Certified English copies of EPO 19305518.3 and EPO 19305768.4 were filed on 10/13/2021.
Claim 19 has been amended to recite “a cleavable linker that is cleaved in vivo”. Support for the new limitation is found at least at paragraph [0056] of the published application “The cleavable linker is any peptide linker that is cleavable in vivo.” and at page 10, lines 20-21 of EPO 19305518.3.
Thus, the earliest possible priority for the instant application is April 19, 2019.
RESPONSE TO ARGUMENTS
Claim objection
Claim 19 is objected to because the recitation of “is cleavable in vivo” is grammatically incorrect. The phrase should use the past tense to the verb “to cleave”. Appropriate correction is requested.
Withdrawn objections/ Rejections in response to Applicants’ arguments or amendments
Specification
In view of Applicants’ amendment of the specification filed on 08/04/2025, the objection to the specification has been withdrawn.
Claim Rejections - 35 USC § 112(b)
In view of Applicants’ amendment of claims 23-24, 28and 32-34, the rejection of claims 23-24, 28-29, and 32-34 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, has been withdrawn.
Claim Rejections - 35 USC § 101
In view of Applicants’ amendment of claims 35-37 to recite “isolated” the rejection of claims 35-37 under 35 U.S.C. 101 has been withdrawn.
Claim Rejections - 35 USC § 102
In view of Applicants’ amendment of claim 1 to recite “a cleavable linker that is cleavable in vivo”, the rejection of claims 19, and 30 under 35 U.S.C. 102(a)(1) as being anticipated by Johnson et. al. (Journal of Bone and Mineral Research, 32(10), 2062–2073, 2017) has been withdrawn.
Though Johnson et al., teaches a human Fc-FGF23 fusion protein coding sequence for a seventy-two amino acid (72aa) human FGF23 c-tail peptide containing a leader peptide, a hinge and a Fc portion of human IgG1, a single GGGGS linker, and the C-terminal 72 amino acids of human FGF23, Johnson et al., does not teach that the GGGGS linker is cleaved in vivo.
Applicant’s arguments with regard to a withdrawn objection/rejection are moot.
Claim Rejections - 35 USC § 103
The rejection of claims 20, 21, 22, 23, 24, 25, 27, 34, 36 and 37 under 35 U.S.C. 103 as being unpatentable over Johnson et. al. (Journal of Bone and Mineral Research, 32(10), 2062–2073, 2017) in view of Luethy et. al. (US 2006/0160181 A1 Date published 2006-07-20; Effectively Filed 2005-09-28) has been withdrawn
A response to Applicant’s arguments with regard to a withdrawn rejection is moot.
The rejection of claim 26 under 35 U.S.C. 103 as being unpatentable over Johnson et. al. (Journal of Bone and Mineral Research, 32(10), 2062–2073, 2017), Luethy et. al. (US 2006/0160181 A1 Date published 2006-07-20; Effectively Filed 2005-09-28), as applied to claims 19 and 25 above, and further in view of Mauro (Bio Drugs 32, 69-81, 2018), has been withdrawn.
A response to Applicant’s arguments with regard to a withdrawn rejection is moot.
The rejection of claim 28 under 35 U.S.C. 103 as being unpatentable over Johnson et. al. (Journal of Bone and Mineral Research, 32(10), 2062–2073, 2017), Luethy et. al. (US 2006/0160181 A1 Date published 2006-07-20; Effectively Filed 2005-09-28), as applied to claim 19 above and further in view of Kramer et. al. (Molecular Therapy Volume 7, Issue 3, p375-385, 2003) has been withdrawn.
A response to Applicant’s arguments with regard to a withdrawn rejection is moot.
Claim 29 under 35 U.S.C. 103 as being unpatentable over Johnson et. al. (Journal of Bone and Mineral Research, 32(10), 2062–2073, 2017), and Luethy et. al. (US 2006/0160181 A1 Date published 2006-07-20; Effectively Filed 2005-09-28) and Kramer as applied to claims 19 and 28 above, and further in view of Nathwani et. al. (Blood Vol. 107, No. 7, 2006), and Mingozzi et. al. (US 2017/0028036 A1; Date published: 2017-02-02; Effectively filed: 2016-10-13) has been withdrawn.
A response to Applicant’s arguments with regard to a withdrawn rejection is moot.
The rejection of claims 31-33 and 35 under 35 U.S.C. 103 as being unpatentable over Johnson et. al. (Journal of Bone and Mineral Research, 32(10), 2062–2073, 2017) and Luethy et. al. (US 2006/0160181 A1 Date published 2006-07-20; Effectively Filed 2005-09-28), as applied to claim 19 above and further in view and Walther et. al. (Drugs 60, 249–271, 2000) has been withdrawn.
A response to Applicant’s arguments with regard to a withdrawn rejection is moot.
New rejections necessitated by amendment of the claims in the responses filed 8/4/2025
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.
Claims 19-25, 27, 30-32 and 34-37 are rejected under 35 U.S.C. 103 as being unpatentable over Mohammadi et. al. (US Patent 10,464,979, citations are from US. Pub. 2017/0226172) in view of Luethy et. al. (US 2006/0160181 A1 Date published 2006-07-20; Effectively Filed 2005-09-28; of record).
Regarding claim 19, Mohammadi et. al. discloses a nucleic acid construct which encodes a Fibroblast growth factor 23 (FGF-23) protein fusions for the treatment of hypophosphatemicdiseases (abstract, [0003][0015]-[0016]), said fusion protein modulates the phosphate pathway in vivo by competitive antagonism of FGF-23 binding to the FGFR/α klotho receptor complex (abstract; para [0010];[0015]) . Mohammadi’s fusion construct comprises a FGF23 c-terminal peptide fused to a heterologous amino acid sequence via a linker (abstract). Specifically “the human Fc-FGF23 fusion protein coding sequence was designed to contain a leader peptide, the hinge of a Human IgG1, a mutated effectorless variant CH2-CH3 region of a human IgG1, a single GGGGS linker, followed by the C-terminal 72 amino acids of human wild type FGF23” (para [0137)]. Moreover, Mohammadi et. al. teaches that the “the FGF23 c-tail proteins are fused to an Fc domain, e.g., one or more domains of an Fc region of a human IgG” (para [0092]) wherein the Fc has a long serum half-life and such that when joined together with a therapeutic protein, an Fc domain can provide longer half-life (para [0092]). Mohammadi et. al. discloses “FGF23 c-tail peptide can effectively compete with full-length FGF23 for binding to each of the three cognate FGFR/aKlotho complexes of FGF23” (para [0097)). In exemplary embodiments Mohammadi et. al. discloses the linker comprises GSGEGEGSEGSG (SEQ ID NO:10); GGSEGEGSEGGS (SEQ ID NO:11); and GGGGS (SEQ ID NO:12). In non-preferred embodiments, Mohammadi et. al., states, “A linker or adapter molecule can also be designed with a cleavage site for a DNA restriction endonuclease or for a protease to allow for the separation of the fused moieties.” (para [0087]).
Therefore, it would have been obvious for one of ordinary skill in the art to generate a nucleic acid construct encoding Mohammadi’s FGF23 fusion proteins where the linker or adapter molecule between the FGF23 c-tail peptide and additional moieties of the fusion protein such as a stabilizing domain Fc domain and a signal peptide, could be selected from a to protease-cleavable linker to allow separation of two moieties in vivo by proteases and wherein said cleavable linker would be reasonably expected to be stable in the absence of a protease. The manipulation of previously identified DNA fragments and cell transformation systems is within the ordinary level of skill in the art of molecular biology. A skilled artisan would have had a reasonable expectation of success as controlling cleavage of two linked moieties in a fusion protein by placing a linker peptide which includes a site for cleavage by a protease in vivo was known in the art before the effective filing date of the invention.
Regarding claim 20, Mohammadi et. al. renders obvious the nucleic acid construct of claim 19. Mohammadi et. al. does not teach a nucleic acid comprising an FGF-23 C- terminal peptide comprising a sequence from any one of positions 175 to 189 to any one of positions 203 to 251 of SEQ ID NO: 1.
However, Luethy et. al. discloses a nucleic acid construct comprising a Fibroblast Growth Factor-23 C-terminal polypeptide sequence that is 100% identical to positions 175 to 251 of SEQ ID NO: 1 in the instant application (see highlighted region in alignment below). Luethy et. al. further discloses the use of such polypeptide to treat, diagnose, ameliorate, or prevent a number of diseases, disorders, or conditions, including hypophosphatemic diseases (para. [0299] and [0302]).
It would have been obvious to one skilled in the art to modify the vector of Mohammadi et. al. to select Luethy’s FGF-23 C-terminal polypeptide comprising a sequence from position 175 to 203 of SEQ ID NO: 1 for Mohammadi’s FGF23 c-tail peptide with a reasonable expectation of success. An artisan would have been motivated to use Luethy’s C-terminal from position 175 to 203 of SEQ ID NO: 1 because Luethy teaches that the peptide can be used to treat, or diagnose a number of diseases.
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Regarding claim 21, Mohammadi et. al. renders obvious the nucleic acid construct of claim 19. Mohammadi et. al. does not teach a nucleic acid construct wherein the FGF-23 C-terminal peptide comprises an RXXR proteolytic cleavage motif in positions 176 to 179 of SEQ ID NO: 1.
However, Luethy et. al. discloses a nucleic acid construct sequence comprising a Fibroblast Growth Factor-23 polypeptide wherein the FGF-23 polypeptide comprises an RXXR proteolytic cleavage motif in positions 176 to 179 that is 100% identical to the RXXR proteolytic cleavage motif sequence in positions 176 to 179 of SEQ ID NO: 1 in the instant application (see highlighted region in alignment below). Luethy et. al. further discloses that a mature FGF-23 polypeptide may include modifications such as proteolytic processing of the amino-terminus (with or without a leader sequence) and/or the carboxyl-terminus, cleavage of a smaller polypeptide from a larger precursor, N-linked and/or O-linked glycosylation, and the like (para [0074]). Luethy further discloses that FGF-23 fusion polypeptides may contain linker or adapter molecules designed with cleavage sites for a DNA restriction endonuclease or for a protease to allow for separation of the fused moieties [0124].
With the aim of cleaving the FGF-23 C-terminal peptide of Mohammadi’s FGF23 fusion proteins it would have been obvious to place Luethy’s RXXR proteolytic cleavage motif at position 176-179 to cleave with a protease recognizing said motif within the amino acid of SEQ ID NO.1. An artisan would have been motivated to use Luethy’s RXXR proteolytic cleavage motif because Mohammadi teaches that cleavage of FGF-23 results in a biologically active c-terminal peptide that is a competitive antagonist of the FGF-23 signaling pathway.
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Regarding claim 22, Mohammadi et. al. renders obvious the nucleic acid construct of claim 19. Mohammadi et. al. does not teach a nucleic acid construct wherein the FGF-23 C- terminal peptide comprises the sequence SEQ ID NO: 2 (FGF C-terminal tail).
However, Luethy et. al. discloses a sequence for a nucleic acid construct encoding a Fibroblast Growth Factor-23 polypeptide that is 100% identical to SEQ ID NO: 2 (see alignment below). Luethy et. al. further discloses the identification polypeptides (such as the FGF C-terminal tail comprised in SEQ ID NO: 2) which have a diagnostic or therapeutic benefit [0003] and [0004]. Luethy also discloses the use of such FGF-23 polypeptides in gene therapy wherein the polypeptide is typically designed to compete with endogenous polypeptide in its biological role [0310].
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Regarding claims 23, 24, and 25, Mohammadi et. al., teaches the components of SEQ ID NO: 12 including an FGF-23 c‐tail fusion protein coding sequence comprising a leader peptide (signal peptide), a hinge (CH2-CH3 region of a human IgG1), a linker, the C-terminal 72 amino acids of human wild type FGF23, fused to an Fc domain, (para [0092];[0137)].
Mohammadi et. al. does not teach the components a nucleic acid construct for a FGF-23 protein comprising a chymotrypsinogen B2 signal peptide of SEQ ID NO: 7; (claim 23 elected species) or a protein stabilizing moiety comprising human serum albumin of SEQ ID NO: 9 (claim 24).
However, Luethy et. al. discloses that a signal, sequence may be used to direct an FGF-23 polypeptide out of the host cell and that typically, a nucleotide sequence encoding the signal sequence is positioned in the coding region of an FGF-23 nucleic acid molecule, or directly at the 5' end of an FGF-23 polypeptide coding region [0164] to secrete an FGF-23 polypeptide from the host cell via [164]. Luethy et. al. teaches that many signal sequences have been identified, and any of those that are functional in the selected host cell may be used in conjunction with an FGF-23 nucleic acid molecule [0164]. Therefore, a signal sequence may be homologous (naturally occurring) or heterologous to the FGF-23 nucleic acid molecule [0164]. Additionally, a signal sequence may be chemically synthesized [0164].
Luethy et. al. also discloses the use of albumin as a stabilizing moiety to enhance therapeutic activity [02050]. Luethy et. al. further discloses albumin is a formulation that can be used for modifying, maintaining, or preserving, for example, the pH, osmolarity, viscosity, clarity, color, isotonicity, odor, sterility, stability, rate of dissolution or release, adsorption, or penetration of the composition [0250].
It would have been obvious to one skilled in the art to modify Mohammadi’s nucleic acid construct for gene therapy coding for a FGF23 fusion protein with Luethy’s chymotrypsinogen B2 as a signal peptide, and albumin as a protein stabilizing moiety. An artisan would have been motivated to use Luethy’s chymotrypsinogen B2 signal peptide and albumin as a protein stabilizing moiety because Luethy teaches that the chymotrypsinogen B2 signal peptide has the benefit of functionalization in the selected host and albumin has the benefit of enhancing therapeutic activity and protein stability.
Regarding claim 27, the combined teachings of Mohammadi et. al. and Luethy et. al. render obvious claims 19 and 25. Moreover, Luethy et. al. teaches that a ribosome binding site is usually necessary for translation initiation of mRNA and is characterized by a Shine-Dalgarno sequence (prokaryotes) or a Kozak sequence (eukaryotes) [0163]. The element is typically located 3’ to the promoter and 5’ to the coding sequence of an FGF-23 polypeptide to be expressed [0163]. Note that the Specification discloses at para [0143], “ he resulting sequences are SEQ ID NO: 57 which comprises the CDS of SEQ ID NO: 13 which encodes the fusion protein of SEQ ID NO: 12, flanked in 5′ with MluI/Kozak (construct no 12 in Table 1)”.
Thus, an artisan would have been motivated to use Luethy’s Kozak sequences to flank the FGF-23 protein (SEQ ID NO: 12) because Luethy teaches that these sites are necessary for translation initiation.
Regarding claim 30-32 and 35, Mohammadi et. al. renders obvious the nucleic acid construct of claim 19. Moreover, Mohammadi et. al. discloses that the nucleic acid construct may be DNA (claim 30), and the vector may be a viral vector (para 0058] (claim 31-32 and 35).
Regarding claim 34, Mohammadi et. al. renders obvious the nucleic acid construct of claims 19 and 31. Mohammadi et. al. does not teach a vector which is a particle or vesicle, in particular lipid-based micro- or nano- vesicle or particle comprising an RNA construct.
However, Luethy teaches a therapeutic composition comprising a vector for gene therapy that may be in the form of a bio-erodible particle that provides for the controlled or sustained release of the product [0255].
It would have been obvious to one skilled in the art to modify the vector of Mohammadi et. al. with Luethy’s bio-erodible particle therapeutic composition because Luethy teaches that this type of vector has the benefit of controlled and sustained release of the product.
Regarding claim 36, Mohammadi et. al. renders obvious the nucleic acid construct of claims 19, 31 and 35 . Mohammadi et. al. does not teach a cell according to claim 36, wherein the cell is a muscle, liver (such as an adult stem cell; see specification page 22, line 26) or hematopoietic cell.
However, Luethy discloses that it may be desirable to treat isolated cell populations such as stem cells with one or more FGF-23 polypeptides [0270]. Luethy also discloses that in order to minimize a potential immunological reaction in patients being administered an FGF-23 polypeptide, as may occur with the administration of a polypeptide of a foreign species, recombinant cells whose ability to produce FGF-23 polypeptides has been augmented by transformation with a gene encoding the desired FGF-23 be used for FGF-23 cell therapy.
It would have been obvious to one skilled in the art to modify the vector of Mohammadi al. with Luethy’s stem cell comprising the FGF-23 polypeptide vector. An artisan would have been motivated to use Luethy’s stem cell comprising the FGF-23 polypeptide because Luethy teaches that this method will minimize a potential immunologic reaction.
Regarding claim 37, Mohammadi et. al. renders obvious the nucleic acid construct of claim 19. Additionally, Mohammadi et. al. teaches vectors comprising said construct and cells comprising said vectors (para 0058]-[0059]) . Mohammadi teaches FGF23 c-tail fusion proteins and pharmaceutical compositions comprising the FGF23 c-tail fusion proteins (abstract).
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Claim 26 is rejected under 35 U.S.C. 103 as being unpatentable over Mohammadi et. al. (US Patent 10,464,979, citations are from US. Pub. 2017/0226172) in view of Luethy et. al. (US 2006/0160181 A1 Date published 2006-07-20; Effectively Filed 2005-09-28; of record) as applied to claims 19 and 25 above , and further in view of Mauro (Bio Drugs 32, 69-81, 2018; of record)
Regarding claim 26, Mohammadi et. al. renders obvious the nucleic acid construct of claim 19, as iterated above in the 103 rejection the content of which is incorporated herein, in its entirety. Moreover, Luethy et. al. discloses nucleic acid variants comprising codons which have been altered for optimal expression of an FGF-23 polypeptide in a given host cell [0151]. Such “codon optimization” can be carried out by a variety of methods, for example, by selecting codons which are preferred for use in highly expressed genes in a given host cell [0151].
Mauro further teaches that codon optimization is a method that is commonly used to increase the expression of biotherapeutic recombinant proteins through the use of synonymous codon mutations in messenger RNA (mRNA) coding regions.
It would have been obvious to one skilled in the art to modify the vector of Mohammadi et. al. with Luethy’s codon optimization methods. An artisan would have been motivated to use Luethy’s codon optimization methods because Mauro teaches that codon optimization will have the benefit of increasing the expression of biotherapeutic recombinant proteins.
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Claim 28 is rejected under 35 U.S.C. 103 as being unpatentable over Mohammadi et. al. (US Patent 10,464,979, citations are from US. Pub. 2017/0226172) as applied to claim 19 above and further in view of Luethy et. al. (US 2006/0160181 A1 Date published 2006-07-20; Effectively Filed 2005-09-28; of record) Kramer et. al. (Molecular Therapy Volume 7, Issue 3, p375-385, 2003).
Regarding claim 19, Mohammadi et. al. renders obvious the nucleic acid construct of claim 19, as iterated above in the 103 rejection the content of which is incorporated herein, in its entirety.
Mohammadi et. al. does not teach the nucleic acid construct according to claim 19, comprising an expression cassette wherein the coding sequence is operably linked a liver-specific promoter such as human alpha-1 antitrypsin.
However, Luethy et. al. discloses a promoter that is operably linked to the molecule encoding the FGF-23 polypeptide [0168]. Luethy further discloses that promoters which may be of interest in controlling FGF-23 gene expression include the alpha 1-antitrypsin gene control region which is active in the liver [0171].
Additionally, Kramer teaches that the alpha 1-antitrypsin promoter a potently directs stable gene expression of transgenes in liver cells when adequate levels of therapeutic proteins need to be produced (see abstract and page 383, column 1, paragraph 4).
It would have been obvious to one skilled in the art to modify the vector of Mohammadi et. al. with Luethy’s human alpha-1 antitrypsin promoter. An artisan would have been motivated to use Luethy’s human alpha-1 antitrypsin promoter because Kramer teaches such promoters have the benefit of potent liver-specific delivery of therapeutic transgenes and adequate levels of therapeutic protein expression.
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Claim 29 is rejected under 35 U.S.C. 103 as being unpatentable over Mohammadi et. al. (US Patent 10,464,979, citations are from US. Pub. 2017/0226172), Luethy et. al. (US 2006/0160181 A1 Date published 2006-07-20; Effectively Filed 2005-09-28; of record), Kramer et. al. (Molecular Therapy Volume 7, Issue 3, p375-385, 2003; of record ) as applied to claims 19 and 28 above, and further in view of Nathwani et. al. (Blood Vol. 107, No. 7, 2006;of record), and Mingozzi et. al. (US 2017/0028036 A1; Date published: 2017-02-02; Effectively filed: 2016-10-13; of record ).
Regarding claims 19 and 28, the combined teachings of Mohammadi, Luethy and Kramer render obvious the nucleic acid construct of claims 19 and 28, as iterated above in the 103 rejection the content of which is incorporated herein, in its entirety.
The combined teachings of Mohammadi, Luethy and Kramer do not teach a nucleic acid construct according to claim 28 further comprising one or more control elements selected from the group consisting of: a human ApoE control region; an intron placed between the promoter and the coding sequence such as a modified FIX intron of SEQ ID NO: 19; and a transcription termination signal such as bovine growth hormone polyadenylation signal.
However, Nathwani teaches a nucleic acid construct comprising a 346-bp human apolipoprotein hepatic control region promoter associated enhancer, and a growth hormone poly-adenylation signal (BGHpA) transcriptional termination signal (see Fig. 1A and page 2654, column 2, paragraph 1). Nathwani also teaches that this construct is a liver-restricted expression cassette that results in an improvement inexpression levels of the therapeutic transgene (see abstract). Nathwani does not teach a modified FIX intron of SEQ ID NO: 19.
However, Mingozzi et. al. teaches a sequence for a modified FIX intron that is 100% identical to SEQ ID NO: 19 in the instant application (see alignment below). Mingozzi et. al. also teaches that such an intron may be introduced to increase mRNA stability and the production of protein [0009].
It would have been obvious to one skilled in the art to modify the vector of Mohammadi with the control elements of Nathwani and Mingozzi. An artisan would have been motivated to modify Mohammadi’s vector because Nathwani and Mingozzi teach that such modifications will result in an improvement expression levels of the therapeutic protein and stability of the mRNA.
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Claim(s) 33 is rejected under 35 U.S.C. 103 as being unpatentable over Mohammadi et. al. ((US Patent 10,464,979, citations are from US. Pub. 2017/0226172), as applied to claims 19 and 31 , and further in view of Luethy et. al. (US 2006/0160181 A1 Date published 2006-07-20; Effectively Filed 2005-09-28; of record) and Walther et. al. (Drugs 60, 249–271, 2000; of record).
Mohammadi et. al. renders obvious the nucleic acid construct of claim 19 , as iterated above in the 103 rejection the content of which is incorporated herein, in its entirety. Moreover, Mohammadi et. al. discloses that the nucleic acid construct may be DNA, and the vector may be a viral vector (para [0058]) (claim 31). Mohammadi et. al. that the viral vector is an adeno-associated virus (AAV) vector.
However, Luethy et. al. discloses an expression vector that is suitable for transformation of a host cell and contains nucleic acid sequences that direct and/or control the expression of inserted heterologous nucleic acid sequences [0066]. Luethy also discloses that in vivo gene therapy may be accomplished by introducing the gene encoding FGF-23 polypeptide into cells via local injection of an FGF-23 nucleic acid molecule or by other appropriate viral or non-viral delivery vectors [0293]. For example, a nucleic acid molecule encoding an FGF-23 polypeptide may be contained in an adeno-associated virus (AAV) vector for delivery to the targeted cells [0293].
Additionally, Walther teaches that such vectors have the benefits of great packaging capacities, broad range of target cell infection, and efficient viral infection and gene transfer, which makes them desirable for the delivery of therapeutic agents (see abstract, and page 260, column 1, paragraph 3.
It would have been obvious to one skilled in the art to modify the vector of Mohammadi et. al. with Luethy’s gene therapy vector. An artisan would have been motivated to use Luethy’s vector because Walther teaches that such vectors have the benefit of being efficient tools for gene delivery of therapeutic agents.
Conclusion
Claims 19-37 are rejected.
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to supervisor Maria G Leavitt whose telephone number is (571)272-1085. The examiner can normally be reached 8:30 am -5:30 pm.
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/MARIA G LEAVITT/ Supervisory Patent Examiner, Art Unit 1634