DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Priority
This application is filed under 35 U.S.C. 371 as a national stage of international application PCT/US2022/029022, filed on Aug 31st, 2022, which claims foreign priority to foreign application no. JP2021-143184, filed on Aug 02, 2021. Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Status of Claims
Claims 1-8 and 11-12 are under consideration.
Specification
Applicant is reminded of the proper language and format for an abstract of the disclosure.
The abstract should be in narrative form and generally limited to a single paragraph on a separate sheet within the range of 50 to 150 words in length. The abstract should describe the disclosure sufficiently to assist readers in deciding whether there is a need for consulting the full patent text for details.
The language should be clear and concise and should not repeat information given in the title. It should avoid using phrases which can be implied, such as, “The disclosure concerns,” “The disclosure defined by this invention,” “The disclosure describes,” etc. In addition, the form and legal phraseology often used in patent claims, such as “means” and “said,” should be avoided.
In the instant case, the abstract of the disclosure is objected to because:
it contains language which can be implied, specifically in the form of the word “disclosed” (i.e., disclosed compositions) [emphasis added].
it is more than 150 words.
It does not mention “method of treatment” which is an essential feature of the invention.
A corrected abstract of the disclosure is required and must be presented on a separate sheet, apart from any other text. See MPEP § 608.01(b).
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Section 33(a) of the America Invents Act reads as follows:
Notwithstanding any other provision of law, no patent may issue on a claim directed to or encompassing a human organism.
Claims 7-8 are rejected under 35 U.S.C. 101 and section 33(a) of the America Invents Act as being directed to or encompassing a human organism. See also Animals - Patentability, 1077 Off. Gaz. Pat. Office 24 (April 21, 1987) (indicating that human organisms are excluded from the scope of patentable subject matter under 35 U.S.C. 101).
Claim 7 recites “a cell”. Claim 8 limits the cell to certain cell types.
The specification does not provide a limiting definition of a cell, and does not expressly exclude cells within a human organism (The Spec in [0010] specifically states: The inventors also confirmed that by introducing the scFv gene into human mesenchymal stem cells by using a bornavirus vector, …). Thus, the term “cell” could reasonably be interpreted as encompassing cells within a human organism, which is non-statutory subject matter.
This rejection may be overcome by amending above claims to recite “an isolated cell” or “non-human cell”.
Claim Rejections - 35 USC § 112
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 1-8 and 11-12 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
The 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).
An original claim may lack written description support when a broad genus claim is presented but the disclosure only describes a narrow species with no evidence that the genus is contemplated. See Ariad Pharms., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1349-50 (Fed. Cir. 2010) (en banc). The written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, reduction to drawings, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus. See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406. See MPEP 2163.
Scope of the Invention
The scope of the claim is broad because of the recitation “and/or” in claim 1. Thus, claim 1 is being given the BRI of comprising a bornavirus vector comprising a nucleic acid encoding an antibody or antibody fragment capable of binding to a mutant SOD1 protein,
the antibody or antibody fragment includes: 1) an antibody having the light-chain variable region with the specified CDRs and a generic heavy-chain, and
2) an antibody having the heavy-chain variable region with the specified CDRs and a generic light-chain.
Thus, the genera are: nucleic acids encoding antibodies, comprising a heavy chain variable region containing CDR1 consisting of an amino acid sequence of GFSLNTSGMG (SEQ ID NO: 1), a heavy chain CDR2 consisting of an amino acid sequence of IWWDDDK (SEQ ID NO: 2), and a heavy chain CDR3 consisting of an amino acid sequence of a ARLGYAMDY (SEQ ID NO: 3), which have binding properties to mutant SOD1 proteins and may have 3 or less amino acid substitutions, and / or a light chain variable region containing a light chain CDR1 consisting of an amino acid sequence of QNVGGTN (SEQ ID NO: 4), a light chain CDR2 consisting of an amino acid sequence of SAS, and a light chain CDR3 consisting of an amino acid sequence of QQYYIYPYT (SEQ ID NO: 5), which may have 3 or less amino acid substitutions (claim 1). Antibody fragments of the above (claims 1 and 4). The broadest reasonable interpretation of the scope of the genera listed above is a peptide, which will bind to mutant SOD1 proteins, such as antibodies or Fab, Fab', F(ab')2, Fv, scFab, scFv, dsFv, ds-scFv, diabody, triabody, tetrabody, or minibody, and wherein the antibody or antibody fragment is a humanized antibody or antibody fragment, though they are not so limited. This interpretation is based on dependent claims 2-4. Thus, such an antibody will bind to mutant SOD1 protein, abrogating its neurotoxicity, which in turn is suitable for treatment of ALS or other diseases wherein mutant SOD1 is expressed [Background of Invention].
Disclosure of a Complete or Partial Structure
Regarding 1) the antibody and allowed substitutions, Applicant discloses the full length sequences of the antibody i.e., SEQ ID NO: 8 and 9 and underscores the position of the CDRs recited. Then applicant describes the making of the antibody; i.e., Production of pCAG-Fct p/mΔG LL GFP-scFv plasmid into which antiSOD1 antibody gene is inserted [0061]. Thus, one type of fragment; i.e., sc-Fv is described.
Regarding 2) Other than sc-Fv described above, no other fragment is described nor is there any discussion on how to identify a fragment, the characteristics that must be shared by fragments etc.,. Furthermore, the "antibody fragment" in the invention could include a fragment that does not bind to an antigen at all, and no information is provided on how to obtain an antibody fragment can bind to the mutant SOD1 which is an antigen.
Each of the above two categories comprises a broad subgenus with diverse members and different structures that affect their functions. Some of those structures may have altered binding capability or other altered function(s).
Species Not Described
For 1) and 2), the sc-Fv described binds to the H46R mutant SOD1 gene. The claims do not recite binding of their scFv to this particular mutant rather, the claims require an scFv with particular sequences with an allowance of up to three substitutions. Further, the specification does not describe the generic heavy-chain or generic light-chain that may be combined with the sc-FV described, and if such a combination will still bind at least to the H46R mutant SOD1 gene.
Knowledge from the State of the Art
The prior art is replete with examples wherein i) the binding property of an antibody is generally greatly affected by the amino acid sequence of the epitope (The interaction between amino acid sidechains of the binding surface is interrupted after substitution, pg. 2, middle para, R col, Dang et al., mAbs, 2023, VOL. 15, NO. 1, 2285285) and ii) the antigen-binding activity of an antibody depends on the amino acid sequences of the six CDRs, and if even one amino acid residue is different from the amino acid sequences constituting the six CDRs, the recognition / binding characteristics to the antigen are highly likely to change significantly (aromatic amino acids are forbidden at VL residue 96 of CR9114, pg. 5, middle para, R col, Teo et al., 2023, Cell Reports 42, 113410).
In light of this background knowledge, it cannot be said that the scFv specifically disclosed in the description of the present application can i) bind to any of the other (200 types [0002] of) mutant SOD1 even if the scFv can bind to the H46R mutant SOD1, or yet undiscovered epitopes ii) it cannot be said that an antibody containing a CDR in which a mutation is introduced into six CDRs in the scFv specifically disclosed in the description of the present application or an antibody in which the CDR of a heavy chain or a light chain has an arbitrary amino acid sequence can bind to a mutant SOD1 protein including H46R mutant SOD1.
Thus, it is not clear how and where substitutions in antibodies may be tolerated and what fragments are considered within the scope of the invention, which retain the function of binding to a mutant SOD1, from the rest of the disclosure.
Structure/Function Correlation
Regarding the genera, as discussed above, Applicant’s claims encompasses particular sequences of CDR with the proviso that they allow for the sequences, working alone or in combination with each other, to bind to mutant SOD1 in gene therapy of ALS and other diseases that will benefit from binding to mutant SOD1 [Background of Invention], while only specific sequences are described in the instant specification without any correlation to what core sequence is encompassed by the recited sequences/fragments. The breadth of the claimed genera is enormously broad with an unfathomable number of structurally divergent and diverse sequences.
Regarding all the sequences with substitutions as claimed, Applicant has not demonstrated possession of any sequence that could be called a CDR that in combination with other CDRs will still work to bind to mutant SOD1 in gene therapy of ALS and other diseases that will benefit from binding to mutant SOD1, other than the full-length sequences identified as SEQ ID NO: 1-5. Similarly, Applicants do not describe all the sequences of fragments as claimed, other than the full-length sequence of an scFv that binds to mutant SOD1 identified as SEQ ID NO: 8-9 (not claimed). The examples do not provide support for the entire genus/subgenera of sequences claimed because the examples show only individual species. The Specification does not provide sufficient evidence that each member of the entire genus of sequences claimed would produce the intended outcome of binding to mutant SOD1. The Specification does not provide specific guidance for determining what the structure of substitutions of sequences or fragments should be that will bind to mutant SOD1; the functional characteristic is not coupled with a known structure.
Altogether, the number of species disclosed by complete structure is not sufficient to provide the written description support for the huge genus of antibodies or fragments capable of binding to mutant SOD1 as claimed.
Dependent Claims
Claims 2-8, and 11-12 do not further limit the genus of nucleic acid molecules so as to resolve the issues above, and are therefore, not sufficiently described for at least the reasons above.
Conclusion of Written Description
While none of these elements is specifically required to demonstrate possession, in combination their lack means that one skilled in the art at the time of filing would conclude that the inventors lacked possession of the invention as recited.
Only an sc-Fv with an amino acid sequence that can bind to H46R mutant SOD1 but not the full breadth of the claims is supported by Applicant’s disclosure.
Scope of Enablement
Claims 11-12 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for a method of treating ALS wherein the disease is characterized by H46R mutant SOD1accumulating, comprising administering an effective amount of the cell of claim 7 to a mammal, does not reasonably provide enablement for a method for treating a disease in which mutant SOD1 accumulates, comprising administering an effective amount of the cell of claim 7 to a mammal. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
The legal considerations that govern enablement determinations pertaining to undue experimentation have been clearly set forth. Enzo Biochem, Inc., 52 U.S.P.Q.2d 1129 (C.A.F.C. 1999). In re Wands, 8 U.S.P.Q.2d 1400 (C.A.F.C. 1988). See also MPEP § 2164.01(a) and § 2164.04. Ex parte Forman 230 U.S.P.Q. 546 (PTO Bd. Pat. App. Int., 1986). The courts concluded that several factual inquiries should be considered when making such assessments including: the quantity of experimentation necessary, the amount of direction or guidance presented, the presence or absence of working examples, the nature of the invention, the state of the prior art, the relative skill of those in that art, the predictability or unpredictability of the art and the breadth of the claims. In re Rainer, 52 C.C.P.A. 1593, 347 F.2d 574, 146 U.S.P.Q. 218 (1965). The disclosure fails to provide adequate guidance pertaining to a number of these considerations as follows:
Nature of the invention/Breadth of the claims
The claims are drawn to method of treating a disease in which SOD1 accumulates, the method comprising administering a cell comprising: a recombinant virus comprising RNA encoded by the bornavirus vector (claim 6) wherein the bornavirus vector comprises a nucleic acid encoding an antibody or an antibody fragment capable of binding to a mutant SOD1 protein (claim 1). Thus, the method relies upon an antibody engineered to bind to mutant SOD1. The specification describes innumerable mutant SOD1 are known to exist. See written description above.
State of the art
With respect to the disease under consideration, ALS, Sah (US 20200239912 A1) also disclose methods of treating ALS by targeting SOD1. Sah disclose innumerable mutations are present in SOD1 gene. Of these, mutations are carried by 15-20% of familial ALS (fALS) patients and by 1-2% of all ALS cases. Currently, at least 170 different mutations distributed throughout the 153-amino acid SOD1 polypeptide have been found to cause ALS, and an updated list can be found at the ALS online Genetic Database (ALSOD) (abstract only: Wroe R et al., Amyotroph Lateral Scler., 2008, 9, 249-250). Sah lists some examples of mutations in SOD1 in ALS, see Table 1.
Predictability of the art
The art is developed sufficiently to allow the skilled artisan to make an antibody given an epitope. However, the art still does not reconcile the use of an antibody designed to target a particular epitope to be sufficiently enabled to target any other epitope with predictability and without undue experimentation. In fact, the art teaches that protein chemistry is probably one of the most unpredictable areas of biotechnology. See written description above. Simply put, even a single substitution can change the biological property of a peptide. Thus, if the biological function of peptide variant is unpredictable then the use of such a peptide, as in instant method, is also unpredictable.
Working examples
In Test Example 2 of the description of the present application, it is described that, as a result of administering to H46R mutant SOD1 transgenic rats oligodendrocyte progenitor cells (OPC) into which a bornavirus vector carrying scFv genes having a heavy chain consisting of an amino acid sequence of a CDR1, IWWDDDK (SEQ ID NO: 1), CDR2 consisting of an amino acid sequence of a heavy chain GFSLNTSGMG (SEQ ID NO: 2), and CDR3 consisting of an amino acid sequence of a ARLGYAMDY (SEQ ID NO: 3) in a VH consisting of an amino acid sequence represented by SEQ ID NO: 8 (heavy chain), and a VL consisting of a light chain CDR1 consisting of an amino acid sequence of a QNVGTN, a light chain CDR2 consisting of an amino acid sequence of a SAS, a QQYYIYPYT (SEQ ID NO: 5), in a VL represented by SEQ ID NO: 9, which have binding properties to H46R mutant SOD1, was introduced, alleviation of ALS symptoms was observed (FIGS. 4A-E). In Test Example 3, it is specifically described that the amount of lumbar spinal SOD1 collected from the H46R mutant SOD1 transgenic mouse transplanted with the OPC was reduced (Fig. 5 6).
Guidance in the specification
However, the art (see state of the art) and paragraph [0002] of the description of the present application describes that there are 200 types of mutations in the SOD1 gene other than the H46R mutant, but considering that the description of the present application does not specifically disclose the epitope of the H46R mutant SOD1 to which the scFv binds, and that it is a well-known fact that the binding property of an antibody is generally greatly affected by the amino acid sequence of the epitope, it cannot be said that the scFv specifically disclosed in the description of the present application has the binding property to the other 200 types of mutant SOD1 even if the scFv can bind to the H46R mutant SOD1. Thus, the specification provides guidance towards administering an scFv that can bind the H46R mutant SOD1 resulting in decrease in lumbar spinal SOD1. The specification provides no clarity regarding any other of the 200 known mutations of SOD1 that may be similarly bound by the claimed scFV.
Amount of experimentation necessary
Since the art teaches that it is unpredictable whether or not peptide variants of known proteins will function as expected, and the specification does nothing to ameliorate these concerns, one would be burdened with undue experimentation to use the products of instant claims as broadly as they are currently claimed.
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 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.
Claim(s) 1-8 are rejected under 35 U.S.C. 103 as being unpatentable over Durocher (WO 2020/056522 A1) in view of Tomonaga (WO/2010/113647).
Claim Interpretation of claim 1:
1. Functional Limitation: the recitation, an antibody or antibody fragment capable of binding to a mutant SOD1 protein, is a clause indicating the function of the invention and so is being considered as a functional limitation.
2. Use of the alternative: Because of the recitation “and/or” in claim 1, claim 1 is being given the BRI of comprising a bornavirus vector comprising a nucleic acid encoding an antibody or antibody fragment capable of binding to a mutant SOD1 protein,
the antibody or antibody fragment comprising:
a heavy-chain variable region …
and/or
a light-chain variable region …; i.e., both are not required to be present.
Regarding claim 1, Durocher teaches a monoclonal antibody (5C9) VL domain, whose sequence is represented by SEQ ID 10, which is a fusion of three CDRs, see table on pg. 33 and claim 11. As seen by the alignment below, Durocher’s light-chain variable region, SEQ ID NO 10, comprises a light-chain CDR1 consisting of an amino acid sequence QNVGTN (SEQ ID NO: 4), a light-chain CDR2 consisting of an amino acid sequence SAS, and a light-chain CDR3 consisting of an amino acid sequence QQYYIYPYT (SEQ ID NO: 5), wherein the light-chain variable region has one amino acid mismatch from instant sequence, which reads on the light-chain variable region optionally having 3 or fewer amino acid substitutions.
RESULT 3
BHN10308
ID BHN10308 standard; protein; 107 AA.
XX
AC BHN10308;
XX
DT 14-MAY-2020 (first entry)
XX
DE Anti-FUT8 monoclonal antibody (5C9) VL domain, SEQ ID 10.
XX
KW FUT8 protein; Fucosyltransferase 8; alpha-(1,6)-fucosyltransferase;
KW antibody production; expression; light chain variable region;
KW monoclonal antibody; protein production.
XX
OS Mus sp.
XX
FH Key Location/Qualifiers
FT Region 7..18
FT /note= "CDR1"
FT Region 36..45
FT /note= "CDR2"
FT Region 85..97
FT /note= "CDR3"
XX
CC PN WO2020056522-A1.
XX
CC PD 26-MAR-2020.
XX
CC PF 20-SEP-2019; 2019WO-CA051345.
XX
PR 21-SEP-2018; 2018US-0734426P.
XX
CC PA (CANA ) NAT RES COUNCIL CANADA.
XX
CC PI Durocher Y, Joubert S;
XX
DR WPI; 2020-237470/031.
XX
CC PT New alpha-(1,6)-fucosyltransferase (FUT8) antibody, its antigen binding
CC PT domain, or its fusion protein useful for inhibiting FUT8 activity in
CC PT cell, comprises variable region of heavy and light chain, antibody or its
CC PT fusion protein.
XX
CC PS Claim 11; SEQ ID NO 10; 55pp; English.
XX
XX
SQ Sequence 107 AA;
Query Match 69.1%; Score 67.7; Length 107;
Best Local Similarity 23.9%;
Matches 17; Conservative 0; Mismatches 1; Indels 53; Gaps 2;
Qy 1 QNVGTN-----------------SAS---------------------------------- 9
|||||| |||
Db 27 QNVGTNVAWYQQKPGQSPKALIYSASYRYSGVPDRLTGSGSGTDFTLTFSYVQSEDLAEY 86
Qy 10 --QQYYIYPYT 18
|||| ||||
Db 87 FCQQYYTYPYT 97
Because the art of Durocher teaches the presence of CDRs that are shown in instant application as binding to a particular mutant SOD1, the art of Durocher reads on the phrase “capable of binding to a mutant SOD1”.
Regarding claim 2, Durocher teaches the antibody is an intrabody (title).
Regarding claim 3, Durocher teaches an embodiment of the antibody may be an scFv [0078].
Regarding claim 4, Durocher teaches a humanized embodiment of the antibody [0041].
Durocher does not teach a bornavirus vector (claim 1) or any limitation related to bornavirus (claims 5-8).
However, before the effective filing date of instant invention, Tomonaga had taught a recombinant viral RNA encoded in a bornaviral vector (title, abstract).
Regarding claim 1, Tomonaga had taught that the viral vector is also useful as an RNA viral vector capable of expressing functional RNA molecules, …e.g., single-stranded antibodies (scFv) [0095].
Regarding claim 5, Tomonaga had taught that the viral vector comprises: (a) cDNA for recombinant viral RNA having such a sequence that at least N gene, X gene, P gene and L gene contained in the genome of a Borna disease virus are arranged in the same order as that in the Borna disease virus and a foreign gene is inserted in a non-translation region linked downstream of a translation region of P gene; (b) DNA encoding a ribozyme; and (c) a promoter sequence, wherein the DNA (b) is located upstream of the cDNA (a) and downstream of the DNA (b), and wherein the cDNA (a) and the DNA (b) are located downstream of the promoter sequence (c) (abstract).
As such, it would have been prima facie obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to have inserted the recombinant construct of a nucleic acid sequence encoding VL of Durocher in to a bornavirus vector because a bornavirus vector was known in the art as a vector suitable for expressing a single chain antibody (scFv). The selection of a known material based on its suitability for its intended use supports a prima facie obviousness determination as taught in MPEP 2144.07. One of ordinary skill in the art would have reasonable expectation of success in making the combination because all references are in field of expressing recombinant antibodies.
Regarding claim 6, the combination of Durocher and Tomonaga as discussed above would result in a recombinant virus comprising RNA encoded by the bornavirus vector of claim 1.
Regarding claim 7, Tomonaga had taught that the viral vector can infect brain neural cells in mammals such as glial cells, neurons in the cerebral cortex, hippocampal neurons, cerebellar neurons, and midbrain neurons [0083].
Regarding claim 8, Tomonaga had some examples of brain neural cells in mammals include glial cells, neurons in the cerebral cortex, hippocampal neurons, cerebellar neurons, and midbrain neurons. Suitable cultured cells for mammalian brain neurons include OL, C6, U373, N2a, N18, PC12, and SK-N-SH cells [0083].
Thus, Durocher in view of Tomonaga make obvious instant claims 1-8.
Note regarding claims 11 and 12:
Regarding claim 11, the cell of claim 7 is made obvious by the combination of Durocher and Tomonaga. Tomonaga had further taught that the viral vector may be associated with a method of treating cranial nervous system diseases wherein the vector is especially useful in infecting brain neurons with the recombinant virus to be produced, such that a causative protein can be decomposed or the expression of the causative protein can be suppressed to prevent or treat the disease [0093].
Neither Durocher nor Tomonaga had taught a method for treating the disease in which mutant SOD1 accumulates, comprising administering an effective amount of the cell of claim 7 to a mammal (claim 11) or wherein the disease in which mutant SOD1 accumulates is amyotrophic lateral sclerosis (claim 12).
Relevant Prior Art Not relied Upon
The following art, of shared inventors, is made note of and not currently relied on, but is relevant to applicants invention. Yokoseki et al., (US 20120177664 A1) have taught different antibodies that specifically bind isolated A beta (Aβ) oligomer as an antigen, for example. It is known that Aβ molecules can misfold and self-assemble into various aggregate states. Mutant SOD1 can comprise misfolded proteins. Sequence of one of the antibodies disclosed by Yokoseki et al., see below, is similar to instant SEQ ID NO: 8 (underlined are instant heavy chain CDRs) except for the fact that there are 4 amino acid changes and so Yokoseki et al’s mAB does not read on the claims. Therefore, Yokoseki’s is not a reference for prior art rejection.
RESULT 9
US-13-389-229-2674
Sequence 2674, US/13389229
Publication No. US20120177664A1
GENERAL INFORMATION
APPLICANT: YOKOSEKI, Tatsuki
APPLICANT: OKAMOTO, Yasuhide
APPLICANT: UMEDA, Makoto
APPLICANT: TAKAMATSU, Naofumi
APPLICANT: ITO, Toshiyuki
APPLICANT: IMAI, Yukiho
APPLICANT: FUJII, Shinobu
TITLE OF INVENTION: ANTIBODIES THAT SPECIFICALLY BIND TO A BETA OLIGOMERS AND USE THEREOF
FILE REFERENCE: 2144.0540002/RWE/SLE
CURRENT APPLICATION NUMBER: US/13/389,229
CURRENT FILING DATE: 2012-03-02
PRIOR APPLICATION NUMBER: PCT/JP2010/004925
PRIOR FILING DATE: 2010-08-05
PRIOR APPLICATION NUMBER: US 61/231,797
PRIOR FILING DATE: 2009-08-06
PRIOR APPLICATION NUMBER: US 61/282,533
PRIOR FILING DATE: 2010-02-26
NUMBER OF SEQ ID NOS: 2976
SEQ ID NO 2674
LENGTH: 117
TYPE: PRT
ORGANISM: Mus musculus
Query Match 88.7%; Score 552; Length 117;
Best Local Similarity 89.7%;
Matches 104; Conservative 4; Mismatches 8; Indels 0; Gaps 0;
Qy 1 QVTLKESGPGILQPSQTLSLTCSFSGFSLNTSGMGVGWIRQPSGRVLEWLAHIWWDDDKR 60
|||||||||||||||||||||||||||||:|||||| |||||||: |||||||:||||||
Db 1 QVTLKESGPGILQPSQTLSLTCSFSGFSLSTSGMGVSWIRQPSGKGLEWLAHIYWDDDKR 60
Qy 61 YNPALKSRLTISKDTSTNQVFLKIASVDTTDTATYYCARLGYAMDYWGHGTSVTVS 116
|||:|||||||||||| ||||||| |||| ||||||||| ||||||| |||||||
Db 61 YNPSLKSRLTISKDTSRNQVFLKITSVDTADTATYYCARYYYAMDYWGQGTSVTVS 116
Conclusion
No claims are allowed.
Correspondence
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SHABANA MEYERING, Ph.D. whose telephone number is (703)756-4603. The examiner can normally be reached M - F: 9am to 5pm EST.
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SHABANA S. MEYERING, Ph.D.
Examiner
Art Unit 1635
/SHABANA S MEYERING/ Examiner, Art Unit 1635
/CATHERINE KONOPKA/ Primary Examiner, Art Unit 1635
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