DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Election/Restrictions
Applicant’s election without traverse of Group II (claims 47- 77) in the reply filed on 12/05/2025 is acknowledged. Election was made without traverse. Therefore, claims 47- 77 are under examination.
Priority
Applicants’ claim for the benefit of a prior-filed application parent provisional application 63330684 filed on 04/13/2022 under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, or 365(c) is acknowledged
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 08/07/2023 was filed before the mailing date of the non-final first action on the merits. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Allowable Subject Matter
It should be noted that sequence search was extended to include all of the SEQ ID NOs recited in claim 69. Sequence search did not find any prior art with 100% identity to the
claimed SEQ ID NOs: 17. Therefore, only SEQ ID No: 17 is free of art.
Claim Objections
Claim 70 is objected to because of the following informalities: the claim recites in line 2 “ polypeptide that comprises or consists in the amino acid” in should be deleted. Appropriate correction is required.
Claim Rejections - 35 USC § 112
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.
Claims 47, 63, and 76 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.
Regarding Claim 47, the claim recites the limitation "the gene construct" in line 2 . There is insufficient antecedent basis for this limitation in the claim.
Regarding Claim 63, the claim recites the limitation "wherein the second promoter" in “The method of claim 60” . There is insufficient antecedent basis for this limitation in the claim.
Regarding claim 76, the claim recites in “The method of claim 76”. In other words, the claim depends from itself . The claim lacks clear antecedent basis..
Regarding claim 77, the claim recites “ the use of claim 50”. There is insufficient antecedent basis for this limitation in the claim.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 47-77are 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 claims require a recombinant nucleic acid comprising a functional variant of the secreted isoform of Klotho (i.e. s-KL). Dependent claims 49-76 depend directly from claim 48.
Upon review of the specification, the “variant “ is defined as protein variants that can involve amino acid modifications that typically fall into one or more of three classes: substitutional, insertional, or deletional variants, whereas "functional" is defined as the variant that would be therapeutically effective in treatment of motor impairment that may occur, for example, in various diseases or disorders such as neuromuscular diseases and disorders.( See paragraph [0064]). While the specification shows that Applicants have provided a full description of the full length of s-KL by disclosing the associated SEQ ID Nos that define the exact nucleic acid sequence; however, the specification fails to disclose any nucleic acid sequences or amino acids that would specifically define the functional variants. Applicants have not provided sufficient description of specific nucleic acid/nucleic acid sequences or motifs that distinguish the said functional variants from the non-functional ones. Furthermore, Applicants have not demonstrated a reduction in practice that the claimed functional variants will perform the claimed function of treating motor impairments at a therapeutically effective levels.
Possession of an invention may be shown in a variety of ways including description of an actual reduction to practice, or by showing that the invention was "ready for patenting" such as by the disclosure of drawings or structural chemical formulas that show that the invention was complete, or by describing distinguishing identifying characteristics sufficient to show that the applicant was in possession of the claimed invention. See, e.g., Pfaff v. Wells Elecs., Inc., 525 U.S. 55, 68, 119 S.Ct. 304, 312, 48 USPQ2d 1641, 1647 (1998).
In the instant case the specification only provides sufficient description, examples, or data of SEQ ID Nos that disclose the full length of the secreted isoform i.e. s-KL. But it fails to disclose the structural features of the claimed functional variants that would perform the claimed function of treating motor impairment at a therapeutically effective levels. The general knowledge and level of skill in the art do not supplement the omitted description because specific, not general, guidance is what is needed. Accordingly, Applicants have not provided sufficient description of the invention to support they were in possession of all the functional variants of s-KL .
Furthermore, claim 58 requires a nucleic acid/ amnio acid sequence that is at least 85%,88%,95% or 98% identical to the claimed SEQ ID NO: 1, which encodes a full-length s-KL. Therefore, claim 58 encompass a large genus of s-KL functional variants with as little as 85% identity to the claimed full-length s-KL that is associated with SEQ ID NO: 1. To begin with, the specification does not provide a written description for obtaining stable and functional variants of s-KL to cover all possible variants of the human s-KL that would result in a sequence with as little as 85% identity to the claimed sequence of SEQ ID NO:1 and producing a stable and functional protein imparting a functional variant activity . Furthermore, the specification does not identify what changes, deletion, substitution, etc could be made to SEQ ID NO: 1 that would still produce a stable and functional variants of the human s-KL. Accordingly, Applicants have not provided sufficient description of the invention to support they were in possession of all sequences having at least 85% sequence identity to SEQ ID NO: 1.
Taken together, the claims are considered to lack sufficient written description and are properly rejected under 35 USC 112, first paragraph. Dependent claims are included in the basis of the rejection because they do not correct the primary deficiencies of the independent claims.
Claim Interpretation
The Klotho protein exists in two forms: membrane Klotho (m-KL) and secreted Klotho (s-KL). According to the specification as recited in paragraph [0054] , the term “mammalian s-KL” or a functional variant thereof, refers to the transcript that is generated from alternative splicing of α-klotho human gene. This isoform comprises of the KL1 domain with an approximate weight of about 63 kDa and a specific secretion signal consisting of a 16-amino acid tail that is not found in the full length (i.e. m-KL) transcript or the protolyzed isoform (i.e. p-KL). In other words, it is noted that the claimed mammalian s-KL and its functional variants, encoded by the nucleic acid described herein, exclude the full-length m-KL and p-KL (containing both KL1-KL2 domains) forms of Klotho.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 48-57,59-74, and 77 are rejected under 35 U.S.C. 103 as being unpatentable over Abraham et al ( WO 2020/039425 A1), in view of Zeldich et al ( Journal of Molecular Neuroscience, 2019), Henricks et al ( Human Molecular, Genetics, 2018), Tarsio et al (WO 2018/098375 A1), Sabater et al ( EP 4046631 A1), Mingozzi et al ( WO 2019/154939 A1),Tabenordbar et al ( Cell, 2021), Grimm et al ( WO 2019/207132 A1), and Xu et al (Biochimica et Biophysica Acta, 2003), as evidenced by Kuro-o et al (Nature, 1997).
Regarding claim 48-54, 59,65- 67,and 77 Abraham et al teach a method for inhibiting tumor growth in a subject in need. The method involves administering a recombinant vector, such as recombinant viral vectors, comprising a muscle-specific promoter (i.e. desmin promoter) operatively linked to a nucleic acid encoding the secreted isoform of Klotho protein (s-KL). ( See page 3-lines 21-31, page 4-lines 3-4). Furthermore, Abraham et al teach a viral vector with a serotype that has a muscle tropism, such as AAV9 , this reads on step (ii) of the instant claim 48 and claims 59, 65-67. (See claims 1-5, and 14-16).
Abraham et al teach a recombinant viral construct expressing s-KL for treating cancer. This differs from instant claims, which are directed to the use of the same viral vector but for the treatment of motor impairment.
Zeldich et al demonstrate that Klotho overexpression in the SOD1G93 A , a mouse model of Amyotrophic Lateral Sclerosis (ALS), provides robust neuroprotection. Specifically, Zeldich et al show that Klotho overexpression in SOD1G93A mouse model suppresses the production of proinflammatory cytokines, reduces the expression of neuroinflammatory markers, and prevents neuronal loss, with a more profound effect in the spinal cord than in the motor cortex, thereby delaying the onset and progression of the disease. ( See abstract). Zeldich et al state that “ Our study provides evidence that increased levels of Klotho alleviate ALS-associated pathology in the SOD1 mouse model and may serve as a basis for developing Klotho-based therapeutic strategies for ALS”. ( See abstract).Taken together, Zeldich et al propose that Klotho-based therapies may improve quality of life, slow disease progression, and extend survival in ALS patients.
It should be noted that Zeldich et al cite Kuro-o et al; (2005),who also cite Kuro-o et al; 1997, as the source reference for the transgenic animal model . ( See page 266,1st column, 2nd paragraph). According to Kuro-o et al (1997), the transgenic mouse model is generated by overexpressing the full-length cDNA of Klotho (i.e. the membrane-bound isoform ,m-KL). ( See Kuro-o et al , 1997, section “Generation of transgenic mice for rescue” on page 51). This differs from the instant claims, which are directed to the overexpression of secreted splice isoform (i.e. s-KL). However, it should also be empathized that once the full length i.e. m-KL is expressed, the secreted form will also be generated through alternative splicing, therefore the transgenic animal model also involves the production of s-KL. In other words, the expression of the s-KL isoform is presumed to be inherent in the teachings of Zeldich et al.
In addition, Henricks et al demonstrate that s-KL derived from macrophages promotes muscle regeneration. Specifically, Henrick et al teach that culturing myoblast in conditioned media collected from Klotho transgenic bone marrow derived macrophages (BMDMs) (i.e. from the mouse model overexpressing Klotho) resulted in substantial increases in myogenic cell counts, which were inhibited by anti-Klotho but not isotype control , when compared to conditioned media from wild-type BMDMs( See Fig.6A). In contrast, conditioned media from Klotho hylomorphic mutant BMDMs did not increase myogenic cell counts, when compared to control cultures (i.e. conditioned media collected from wild-type derived BMDMs) (Fig.6A).
Taken together, employing an expression vector encoding for s-KL under the control of a muscle-specific promoter to treat motor impairment, such as the one experienced by ALS patients, is a product of combining prior art elements according to known methods to yield predictable results. Abraham et al teach a recombinant viral construct expressing s-KL for treating cancer, but fail to suggest using the construct to treat motor impairment in a subject in need. Zeldich et al provide evidence that increased levels of Klotho alleviate ALS-associated pathology in the SOD1 mouse model, and suggest that Klotho-based therapies may be used to improve quality of life, slow disease progression, and extend survival in ALS patients. The teachings of Henricks et al demonstrate that exposing muscle stem cells (i.e. myoblast) to s-KL promotes muscle regeneration. Thus, one would have been motivated to use the recombinant vector expressing the s-KL under the control of a muscle-specific promoter, as taught by Abraham, to treat motor impairment in patients with ALS. One would be motivated to employ the recombinant vector of Abraham to specifically deliver the s-KL to the affected muscle rather than using the transgenic mouse model of Zeldich, which would have the inconvenient of having this protein expressed ubiquitously (body and brain). A person of ordinary skill in the art who had reviewed Abraham could have come across Zeldich and Henricks and immediately noticed the strong possibility that the use of the expression vector of Abraham , instead of the transgenic animal model of Zeldich, would have predictable results of using a recombinant vector with an increased tropism to muscle tissue to specifically deliver the therapeutic protein (i.e. s-KL) to the injured muscle rather than the whole body, which is especially relevant in gene therapy applications to treat disease with muscle impairment.
Regarding claims 55-56, Abraham et al contemplate that, in some embodiments, the methods comprise systemically administering the viral vector expressing a klotho protein, with parenteral systemic administration. In other embodiments, Abraham et al also contemplate that the method of delivery can be intravenous, intrathecally administered, or via intramuscular injection.
Regarding claim 57, following the discussion above, Abrahm et al in view of Zeldich and Henricks et al render obvious a viral construct encoding s-KL for the treatment of motor impairment. However, Abrahm et al do not teach the viral construct encoding SEQ ID NO:1.
Tarsio et al disclose a nucleic acid construct or vector that encodes a recombinant human s-KL having the amino acid sequence of SEQ ID NO: 41 that is 100% identical to SEQ ID NO:1 of the instant claim. Tarsio et al also teach that the expression vector can be employed therapeutically to treat muscle atrophy in humans. Furthermore, Tariso et al also suggest using the recombinant vector expressing s-KL to treat patients with ALS disease. (See [0009], [0198], and [0034]).
Therefore, claim 57 is also a product of combining prior art elements according to known methods to yield predictable results, the predictable results being the generation of a recombinant viral construct encoding SEQ ID 41 to treat muscle impairment. Abraham et al in view of Zeldich and Henricks render obvious a recombinant viral construct expressing s-KL for treating motor impairment, but they fail to suggest using construct comprising SEQ ID NO:1. Tariso et al teach a viral construct comprising SEQ ID NO:41, which shares 100% identity with SEQ ID NO:1 of instant claim, and clearly suggest that the construct can be employed to treat muscle atrophy and age-related diseases such as ALS. Therefore, a person of ordinary skill in the art who had reviewed Abraham, Zeldich, and Henricks, could have come across Tarsio and immediately noticed the strong possibility of using an expression vector comprising SEQ ID 41 to treat motor impairment in patient in need. A person of ordinary skill in the art would have a reasonable expectation of success, when building an expression vector, that taking SEQ ID 41 as described by Tarsio, and placing it under the control of desmin promoter as described by Abraham, that the vector of claim 48 would be successfully synthesized.
Regarding claims 59 and 60, following the discussion above, the combined teachings of Abrahm, Zeldich, and Henricks render obvious a viral construct encoding s-KL under the control of desmin promoter. However, none of the recited prior art specifically teaches viral construct comprising human desmin promoter, wherein the human desmin promoter has the nucleic acid sequence of SEQ ID NO:5.
Sabater et al teach an adeno-associated virus (AAVs) vectors comprising of human desmin promoter (hDES) to drive the expression of isoform 4 of murine Msi2 in muscle cells. It should be noted that Sabater’s construct comprises human desmin promoter with SEQ ID NO: 69, that share 100% identity with SEQ ID NO:5 of the instant claim. (See page 33-lines 4-21).
Therefore, claims 59-60 are also a product of combining prior art elements according to known methods to yield predictable results, the predictable results being the generation of a recombinant viral construct comprising the human desmin promoter to drive the expression of s-KL in muscle tissues. The combined teachings of Abrahm, Zeldich, and Henricks render obvious a viral construct encoding for s-KL under the control of desmin promoter, but fail to suggest using construct comprising of human desmin with SEQ ID NO:5. Sabater et al teach a viral construct comprising SEQ ID NO:69, which share 100% identity with SEQ ID NO:5 of instant claim, to drive the expression of Msi2 in murine muscle cells. Therefore, a person of ordinary skill in the art who had reviewed the cited prior arts could have come across Sabater and immediately noticed the strong possibility of using an expression vector comprising SEQ ID NO:5 would have the predictable results of driving the expression of s-KL specifically into muscle tissue, because desmin promoter is a muscle-specific promoter.
Regarding claims 62-64, following the discussion above, the combined teachings of Abrahm, Zeldich, and Henricks render obvious a viral construct encoding for s-KL under the control of desmin promoter. However, none of the cited prior art teach gene construct comprising a first and second promoter, wherein the two promoters are different.
Mingozzi et al teach composite transcription regulatory element to drive gene expression in different tissues in a tissue-selective manner. The composite transcription regulatory element comprises hybrid promoters, which are created by fusing at least two different promoters to drive gene expression in different tissues. (See abstract). Mingozzi et al also teach that the second promoter can be a constitutive promoter or selected from a list of tissue-specific promoters that can drive the expression of the transgene into muscle or neurons. ( See claims 1-3). According to Mingozzi et al, using an expression vector comprising of multiple tissue-selective promoters has the advantage of driving high transgene expression in desired tissues in a selective way. (page 3-lines 13-25).
Therefore, claims 62-64 would have been obvious to one of ordinary skill in the art, as there was some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention. The combined teachings of Abrahm, Zeldich, and Henricks render obvious a viral construct encoding for s-KL under the control of desmin promoter, which is a muscle-specific promoter, but they fail to suggest using an expression construct comprising of a second promoter to drive the expression of s-KL in multiple tissues. Mingozzi et al utilize a composite transcription regulatory element to drive gene expression in different tissues in a tissue-selective manner. Thus, one would have been motivated to use a composite nucleic acid comprising of two promoters to drive s-KL expression in different tissues. There would be a reasonable expectation of success, when building the AAV vector, that taking the vector of Abraham, and adding a second promoter that is different from the first promoter, to drive the expression of s-KL in different tissues in a tissue-selective manner, that the vector of claim 48 could be successfully synthesized.
Regarding claims 68, following the discussion above, Abraham et al also do not teach AAVmyo vector.
Tabenordbar et al teach an evolved family of RGD-containing AAV capsid variants ( known as AAVmyo) in mice and primates that enable highly effective systemic gene delivery to muscles. Tabenordbar et al also show that these capsids are dependent on integrin heterodimers for transduction across species and enable achieving therapeutic efficacy after systemic administration at low dose.( See abstract).Therefore, the subject matter of claim 68, is also obvious in view of the combination of Abraham, Zeldich, Henricks, and Tabenordbar, as there was some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention. The combined teachings of Abrahm, Zeldich, and Henricks render obvious a viral construct encoding for s-KL under the control of desmin promoter to treat motor impairment, but fail to suggest using AAVmyo vector. Tabenordbar et al teach an evolved family of RGD-containing AAV capsid variants ( i.e. AAVmyo) in mice and primates that enable highly effective systemic gene delivery to muscles. Thus, one would have been motivated to use AAVmyo vector to enable highly effective systemic s-KL delivery to muscles. There would be a reasonable expectation of success, when constructing the AAV vector, that taking the AAVmyo vector described by Tabenordbar and combining it with the gene construct of Abraham to drive s-KL expression in muscle tissue, that the vector of claim 48 could be successfully synthesized.
Regarding claims 69-70, Abraham et al do not teach an AAV vector comprising an AAV capsid polypeptide that comprises or consists the amino acid sequence of SEQ ID NO:26.
Grimm et al teach an adeno-associated virus (AAV) capsid polypeptide comprising amino acid sequence of SEQ ID NO:28 which share 100% identity with the instant SEQ ID NO:26. Grimm et al teach that the aforementioned capsid is useful for muscle regeneration or for treating or preventing muscular disease. ( See abstract).
Taken together, the subject matter of claims 69-70, is also obvious in view of the combination of Abraham and Grimm, as there was some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention. The combined teachings of Abrahm, Zeldich, and Henricks render obvious a viral construct encoding for s-KL under the control of desmin promoter to treat motor impairment, but fail to suggest using AAV vector comprising an AAV capsid with SEQ ID NO28. Grimm et al teach an AAV capsid polypeptide that share 100% sequence identity with the instant SEQ ID NO:26 and suggest that an AAV vector comprising the capsid polypeptide would allow for effective delivery to muscle tissue. Thus, one would have been motivated to use an AAV vector comprising an AAV capsid polypeptide comprising of SEQ ID 28, as taught by Grimm et al, to achieve effective systemic s-KL delivery to muscle tissues. There would be a reasonable expectation of success, when building the AAV vector, that taking the AAV capsid polypeptide, as described by Grimm, and Abraham’s gene construct to drive s-KL expression in muscle tissue, that the vector of claim 48 could be successfully synthesized.
Regarding claims 71-73,following the discussion of claim 47, Abraham et al teach an AAV vector comprising of at least one non-coding regulatory element such as poly A sequence, and 5’ and 3’ inverted terminal repeats. ( See page 8-lines 22-27).
Regarding claims 74, Abraham et al in view of Zeldich et al and Henricks et al render obvious claim 48. However, none of the cited prior art teach the use of an AAv vector comprising the following element: i.e. the WPRE element
Xu et al teach that the utilization of AAv vector for gene therapy can be optimized by including transcriptional and post-transcriptional elements such as a promoter, enhancer, intron, and a poly(A) sequence. As a result, including such elements would improve the expression efficiency of each viral particle, allowing for fewer viral particles to be injected. (See Introduction, 2nd column 1st paragraph page 266). For example, Xu et al teach that inserting the woodchuck hepatitis virus post-transcriptional regulatory (WPRE), a powerful viral enhancer element, between the luciferase gene and the poly(A) in an AAv construct encoding for luciferase, increased luciferase expression 2- to 7-fold in vitro and 2- to 50-fold more in vivo. (See abstract and Material and Methods section 2.1. “ adenovirus vectors” page 267). Hence, the subject matter of claims 74, is also obvious in view of the combination of the Abraham and Xu et al, as there was some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention. The combined teachings of Abrahm, Zeldich, and Henricks render obvious a viral construct encoding for s-KL under the control of desmin promoter to treat motor impairment, but fail to suggest using AAV vector comprising an enhancer element such as WPRE. Xu et al teach that the inclusion of the WPRE, along with other regulatory elements such as poly A sequence, substantially reduces the number of viral particles that must be injected to achieve a therapeutic level of transgene expression. Thus, one would have been motivated to use an AAV vector comprising WPRE element, as taught by Xu et al, to reduce the number of viral particles that must be injected to achieve a therapeutic level of s-KL expression. There would be a reasonable expectation of success, when building the AAV vector, that taking the WPRE element as described by Grimm, and incorporating it in the gene construct of Abraham to drive s-KL expression in muscle tissue, that the vector of claim 48 could be successfully synthesized.
Claims 47-48, and 75-76 are rejected under 35 U.S.C. 103 as being unpatentable over Abraham et al ( WO 2020/039425 A1), in view of Gunther et al ( WO 2016/135295 A1), and Mingozzi et al ( WO 2019/154939 A1).
Regarding claims 47,48, and 75-76, the teachings of Abraham et al are set forth above, Abraham et al teach a gene construct comprising nucleic acid encoding s-KL ,wherein the expression of s-KL is under the control of a muscle-specific promoter such as desmin. However, Abraham et al do not teach an isolated cells comprising the said gene construct.
Gunther et al disclose a genetically modified mesenchymal stem cell (MSC) containing s-KL encoding region operably linked to a constitutive promoter. ( See abstract, and page 18-lines 36-39). According to Gunther et al, the genetically modified mesenchymal stem cell can be used as a medicament, with the said cell being administered in a subject in need by introducing a therapeutically effective number of cells into the bloodstream of a subject for the treatment of several diseases, one of which is ALS. ( See page 21-lines 29-30).
Neither Abraham nor Gunther teach an isolated cells expressing the gene construct of claim 47, wherein the cell is a muscle cell including skeletal or striated muscle cell.
The teachings of Mingozzi et al are set forth above.
Mingozzi et al further teach an expression cassette comprising a transgene of interest, wherein the transgene may be a therapeutic transgene that can be used in medicament. Mingozzi et al further teach an isolated cell transformed with the said expression cassette that can also be used to treat motor disease such as ALS, where the isolated cells can be muscle or neuronal cells. ( See page 5 lines 20-31, and page 66 lines 5-17). Mingozzi et also teach that the transformed cells may be delivered to the subject in need thereof via injection in the tissue of interest or in the bloodstream of said subject. ( See page 34 lines 15-22). It should be noted that under the broadest reasonable interpretation, the teachings of Mingozzi et al further include an isolated skeletal or striated muscle.
Taken together, the subject matter of instant claims, are obvious in view of the combination of Abraham, Gunther, and Mingozzi, as there was some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention. Abraham et al teach a viral construct encoding for s-KL under the control of desmin promoter to treat cancer, but fail to teach an isolated cells transformed with the said expression construct to treat motor impairment. Gunther et al teach a genetically modified mesenchymal stem cell (MSC) containing s-KL encoding region and clearly suggest the use of the transformed cells in the treatment of diseases such as ALS. Mingozzi et al also teach that muscle or neuronal cells can be transformed with an expression construct encoding a therapeutic transgene and then given to a patient in need via injection in the targeted tissue or in the bloodstream. Thus, one would have been motivated to utilize genetically modified neuronal or muscle cells comprising an expression construct encoding s-KL to treat motor impairment. There would be a reasonable expectation of success, when building a cell therapy, that taking the expression construct of Abraham to genetically modify MSC, muscle, or neuronal cells, that the cell therapy of claims 47-48 could be successfully synthesized.
Conclusion
No claim is allowed.
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/FATIMAH KHALAF MATALKAH/Examiner, Art Unit 1638
/Tracy Vivlemore/ Supervisory Primary Examiner, Art Unit 1638