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
This action is in response to the papers filed December 23, 2025.
Amendments
Applicant's response and amendments, filed December 23, 2025, to the prior Office Action is acknowledged. Applicant has cancelled Claims 1-17, 19-28, 35, and 39-43, amended Claims 18, 31, and 38, and added new claims, Claims 44-46
Claims 18, 29-34, 36-38, and 44-46 are pending.
Election/Restrictions
Applicant has elected without traverse the following species, wherein:
i) the alternative IGF-1 nucleotide SEQ ID NO is SEQ ID NO:3, as recited in Claim 3;
ii) the alternative IGF-1 amino acid SEQ ID NO is SEQ ID NO:23, as recited in Claim 2;
iii) the alternative miRNA is miRNA-122a, and its corresponding target sequence SEQ ID NO is SEQ ID NO:8, as recited in Claim 4; and
iv) the alternative target tissue in which IGF-1 is to be prevented is liver, as recited in Claim 19 (liver).
Claims 18, 29-34, 36-38, and 44-46 are pending and under consideration.
Priority
This application is a division of application 15/532,958 filed on June 2, 2017, now U.S. Patent 11,085,055, which is a 371 of PCT/EP2015/078878 filed on December 7, 2015.
Acknowledgment is made of Applicant’s claim for foreign priority under 35 U.S.C. 119(a)-(d). A
While certified copy of the foreign patent application EPO 14196536.8 filed on December 5, 2014 is provided with the parent application 15/532,958, a certified English translation of said foreign patent application has not been provided.
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 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 of this title, 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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under 35 U.S.C. 103(a) 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.
1. Claims 18, 31-33, and 36-37 are rejected under AIA 35 U.S.C. 103 as being unpatentable over Kingsman et al (WO 08/071959; of record in IDS) in view of Kelly et al (2009; of record in IDS), Xie et al (2011; of record in IDS), Scheule et al (U.S. 2010/0216709; of record), Barton (WO 14/012025; of record in IDS), Kasprzak et al (2013; of record), and Alberini et al (US20030166555; of record).
Determining the scope and contents of the prior art, and Ascertaining the differences between the prior art and the claims at issue.
With respect to Claims 18 and 38, Kingsman et al is considered relevant prior art for having disclosed a gene construct comprising:
i) a nucleotide sequence encoding a mammalian insulin-like growth factor 1 (IGF-1) (pg 7, ¶4); and
ii) at least one target sequence of a microRNA that is expressed in a tissue in which expression of IGF-1 resulting from the gene construct is to be prevented (pg 7, ¶5),
wherein the nucleotide sequences of (i) and (ii) are each operably linked to a ubiquitous promoter (pg 14, ¶3).
Kingsman et al disclosed wherein the vector is a retroviral vector (pg 9, ¶2), or a lentiviral vector (pg 11, ¶2).
Kingsman et al disclosed wherein the miR binding sites are for miR-1b/d, miR-133, or miR-206 (e.g. pg 6; pg 50).
Kingsman et al do not disclose wherein the expression construct further comprises at least one target sequence of a miRNA expressed in the liver, e.g. miRNA-122a.
However, before the effective filing date of the instantly claimed invention, Kelly et al is considered relevant prior art for having reviewed the use of miRNA target sequences in expression vectors to thereby regulate and/or restrict expression of the vector in the desired target tissue.
Kelly et al taught that target elements to multiple miRNAs engineered within a single vector can increase gene silencing in multiple tissues (pg 411, col. 1), whereby miR-122a target sites are useful to inhibit expression in the liver and miR-1, miR-133, or miR-206 target sites, as per Kingsman et al, are useful to inhibit expression in the heart (Table 1).
By incorporating tandem copies of the miRT for the liver-specific miR-122a, it has been shown that liver expression can be reduced up to 1,500-fold (e.g pg 413, col. 1).
Xie et al is considered relevant prior art for having taught that intravascular delivery of rAAV vectors efficiently target transduction of liver, heart, and skeletal muscles, which may cause undesirable effects (Abstract; pg 527, col. 1). To solve this problem, Xie et al engineered a rAAV expression vector to comprise miRNA target sequences.
Xie et al introduced miR-1 and/or miR-122 target sites into an rAAV vector (e.g. pg 527, col. 1, “complementary sites for miR-1, miR-122, or both were engineered…”).
Xie et al taught that the AAV-encoded transgene comprising miR-1 and miR-122 target binding sites was readily detectable in pancreas, but not heart or liver (e.g. pg 528, col. 2).
Kingsman et al do not disclose the IGF-1 expression vector to be an adeno-associated viral expression vector.
However, before the effective filing date of the instantly claimed invention, Scheule et al disclosed a gene construct encoding IGF-1 operably linked to a ubiquitous or constitutive promoter, e.g. CMV promoter [0047], wherein the viral vector may be a retrovirus, lentivirus, adenovirus, or adeno-associated virus (AAV) [0046].
Similarly, Barton disclosed a gene construct comprising:
i) a nucleotide sequence encoding a mammalian insulin-like growth factor 1 (IGF-1) operably linked to a ubiquitous promoter (pg 5, lines 31-34), wherein the expression vector is an adeno-associated virus (AAV) (Examples 1-2).
Barton disclosed the IGF-1 may be a prepro-IGF-1 protein (e.g. pg 30, Example 1; Figure 2E) comprising the signal peptide, IGF-1, and the EA- and EB-peptides.
Neither Kingsman et al, Scheule et al, nor Barton disclose wherein the IGF-1 is a human preproIGF-1, isoform 2 (syn. SEQ ID NO:23).
However, before the effective filing date of the instantly claimed invention, Kasprzak et al is considered relevant prior art for having taught that the human IGF-1 gene encodes 6 isoforms (Figure 1).
Alberini et al is considered relevant prior art for having disclosed expression vectors, including viral vectors, e.g. retroviral vectors [0171], comprising a nucleic acid molecule encoding IGF-1 preproprotein, isoform 2 (SEQ ID NO:8) [0069, 105-106], wherein SEQ ID NO:8 is 100% identical to instant SEQ ID NO:23.
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With respect to Claim 18, Scheule et al disclosed the AAV may be of serotype 8 [0067].
Xie et al taught wherein the AAV is an AAV9 serotype (e.g. pg 533, col. 2, Methods, “AAV9 vectors”).
An AAV comprising an AAV8 capsid serotype is obvious. M.P.E.P. §2144.07 states "The selection of a known material based on its suitability for its intended use supported a prima facie obviousness determination in Sinclair & Carroll Co. v. Interchemical Corp., 325 U.S. 327, 65 USPQ 297 (1945).” “Reading a list and selecting a known compound to meet known requirements is no more ingenious than selecting the last piece to put in the last opening in a jig-saw puzzle." 325 U.S. at 335, 65 USPQ at 301.).” When substituting equivalents known in the prior art for the same purpose, an express suggestion to substitute one equivalent component or process for another is not necessary to render such substitution obvious. In re Fout, 675 F.2d 297, 213 USPQ 532 (CCPA 1982). M.P.E.P. §2144.06.
Resolving the level of ordinary skill in the pertinent art.
People of the ordinary skill in the art will be highly educated individuals such as medical doctors, scientists, or engineers possessing advanced degrees, including M.D.'s and Ph.D.'s. Thus, these people most likely will be knowledgeable and well-read in the relevant literature and have the practical experience in molecular biology, genetics, virology, and gene delivery and gene therapy methods. Therefore, the level of ordinary skill in this art is high.
"A person of ordinary skill in the art is also a person of ordinary creativity, not an automaton." KSR International Co. v. Teleflex Inc., 550 U.S. ___, ___, 82 USPQ2d 1385, 1397 (2007). "[I]n many cases a person of ordinary skill will be able to fit the teachings of multiple patents together like pieces of a puzzle." Id. Office personnel may also take into account "the inferences and creative steps that a person of ordinary skill in the art would employ." Id. at ___, 82 USPQ2d at 1396.
Considering objective evidence present in the application indicating obviousness or nonobviousness.
The focus when making a determination of obviousness should be on what a person of ordinary skill in the pertinent art would have known at the time of the invention, and on what such a person would have reasonably expected to have been able to do in view of that knowledge. This is so regardless of whether the source of that knowledge and ability was documentary prior art, general knowledge in the art, or common sense. M.P.E.P. §2141.
The rationale to modify or combine the prior art does not have to be expressly stated in the prior art; the rationale may be expressly or impliedly contained in the prior art or it may be reasoned from knowledge generally available to one of ordinary skill in the art, established scientific principles, or legal precedent established by prior case law. In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988); In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992). See also In re Kotzab, 217 F.3d 1365, 1370, 55 USPQ2d 1313, 1317 (Fed. Cir. 2000) (setting forth test for implicit teachings); In re Eli Lilly & Co., 902 F.2d 943, 14 USPQ2d 1741 (Fed. Cir. 1990) (discussion of reliance on legal precedent); In re Nilssen, 851 F.2d 1401, 1403, 7 USPQ2d 1500, 1502 (Fed. Cir. 1988) (references do not have to explicitly suggest combining teachings); and Ex parte Levengood, 28 USPQ2d 1300 (Bd. Pat. App. & Inter. 1993) (reliance on logic and sound scientific reasoning). See MPEP §2144.
Prior to the effective filing date of the instantly claimed invention, it would have been obvious to one of ordinary skill in the art to substitute a first viral vector as disclosed by Kingsman et al, with a second vector, i.e. AAV, as disclosed by Scheule et al and/or Barton, with a reasonable expectation of success because the simple substitution of one known element for another would have yielded predictable results to one of ordinary skill in the art at the time of the invention. M.P.E.P. §2144.07 states "The selection of a known material based on its suitability for its intended use supported a prima facie obviousness determination in Sinclair & Carroll Co. v. Interchemical Corp., 325 U.S. 327, 65 USPQ 297 (1945).” “Reading a list and selecting a known compound to meet known requirements is no more ingenious than selecting the last piece to put in the last opening in a jig-saw puzzle." 325 U.S. at 335, 65 USPQ at 301.).” When substituting equivalents known in the prior art for the same purpose, an express suggestion to substitute one equivalent component or process for another is not necessary to render such substitution obvious. In re Fout, 675 F.2d 297, 213 USPQ 532 (CCPA 1982). M.P.E.P. §2144.06. An artisan would be motivated to substitute a first viral vector, e.g. retroviral or lentiviral vector, with a second vector, i.e. AAV because Scheule et al disclosed that the IGF-1 expression vector may be expressed via any viral vector such as a retrovirus, lentivirus, adenovirus, or adeno-associated virus (AAV), and successfully demonstrated the ability of the routineer to express IGF-1 from an AAV vector [0106], as also demonstrated by Barton et al (Examples 1-2).
Prior to the effective filing date of the instantly claimed invention, it also would have been obvious to one of ordinary skill in the art to substitute a first IGF-1 polypeptide, as disclosed by Kingsman et al, Scheule et al and/or Barton, with a second IGF-1 polypeptide, to wit, IGF-1 preproprotein, isoform 2, as disclosed by Alberini et al, in a rAAV expression vector with a reasonable expectation of success because the simple substitution of one known element for another would have yielded predictable results to one of ordinary skill in the art at the time of the invention. M.P.E.P. §2144.07 states "The selection of a known material based on its suitability for its intended use supported a prima facie obviousness determination in Sinclair & Carroll Co. v. Interchemical Corp., 325 U.S. 327, 65 USPQ 297 (1945).” “Reading a list and selecting a known compound to meet known requirements is no more ingenious than selecting the last piece to put in the last opening in a jig-saw puzzle." 325 U.S. at 335, 65 USPQ at 301.).” When substituting equivalents known in the prior art for the same purpose, an express suggestion to substitute one equivalent component or process for another is not necessary to render such substitution obvious. In re Fout, 675 F.2d 297, 213 USPQ 532 (CCPA 1982). M.P.E.P. §2144.06. An artisan would be motivated to substitute a first IGF-1 polypeptide with a second IGF-1 polypeptide, to wit, IGF-1 preproprotein, isoform 2 in a rAAV expression vector because those of ordinary skill in the art previously recognized that the human IGF-1 gene encodes six isoforms (Kasprzak et al), whereby expression of IGF-1 preproprotein, isoform 2 whose amino acid sequence is 100% identical to instant SEQ ID NO:23 from a recombinant expression vector, including viral expression vectors, had long-been recognized by those of ordinary skill in the art (Alberini et al ).
Prior to the effective filing date of the instantly claimed invention, it also would have been obvious to one of ordinary skill in the art to modify a viral expression vector, including a rAAV viral expression vector, encoding IGF-1 and at least one miR target site for a miRNA expressed in heart tissue, e.g. miR-1 target site, as disclosed by Kingsman et al, to further comprise at least one miR target site for a miRNA expressed in liver, e.g. a miR-122a target site, with a reasonable expectation of success because Kelly et al taught that the miR-122a target sequence is useful to inhibit expression in the liver (Table 1), and by incorporating tandem copies of the miR target sites for the liver-specific miR-122a in an expression vector, it has been shown that liver expression can be reduced up to 1,500-fold (e.g pg 413, col. 1), whereby the choice of miRNA target sites depends upon the artisan’s cell type and tissue of choice (pg 411, col. 1), and Xie et al taught that intravascular delivery, or other forms of systemic administration, of rAAV vectors efficiently target transduction of liver, heart, and skeletal muscles, which may cause undesirable effects (Abstract; pg 527, col. 1). Off-target transduction raises the spectre of overexpression outside the target tissue, potentially eliciting toxic responses (e.g pg 526, col. 2). To solve this problem, Xie et al successfully reduced to practice engineering a rAAV expression vector to comprise both miR-1 and miR-122 target sites into an rAAV vector (e.g. Figure 2c, three miR-1 binding sites and three miR-122 binding sites). Xie et al taught that the AAV-encoded transgene comprising miR-1 and miR-122 target binding sites was readily detectable in pancreas, but not heart or liver (e.g. pg 528, col. 2).
It is proper to "take account of the inferences and creative steps that a person of ordinary skill in the art would employ." KSR Int'l Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741,82 USPQ2d 1385, 1396 (2007). See also Id. At 1742, 82 USPQ2d 1397 ("A person of ordinary skill is also a person of ordinary creativity, not an automaton.").
It should be noted that the KSR case forecloses the argument that a specific teaching, suggestion, or motivation is required to support a finding of obviousness. See the recent Board decision Ex parte Smith, —USPQ2d—, slip op. at 20, (Bd. Pat. App. & Interf. June 25, 2007) (citing KSR, 82 USPQ2d at 1396) (available at http: www. uspto.gov/web/offices/dcom/bpai/prec/fd071925 .pdf).
With respect to Claims 31-32, Kingsman et al disclosed the miR target may be a miR-1 target site (e.g. pg 6, para 3), and as many as four copies of a miR target sequence are cloned into the gene construct (pg 50, Example 2).
Xie et al successfully reduced to practice engineering a rAAV expression vector to comprise both miR-1 and miR-122 target sites into an rAAV vector (e.g. Figure 2c, three miR-1 binding sites and three miR-122 binding sites).
In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). It is routine procedure to optimize component amounts to arrive at an optimal product that is superior for its intended use, since it has been held where the general conditions of a claim are disclosed in the prior art, discovering the optimum or workable ranges involves only routine skill in the art. Similarly, a prima facie case of obviousness exists where the claimed ranges or amounts do not overlap with the prior art but are close enough that one skilled in the art would have expected them to have the same properties. See M.P.E.P. §2144.05(I).
With respect to Claim 33, Kingsman et al disclosed wherein the promoter is a constitutive promoter, e.g. CMV promoter (pg 14, ¶3).
Scheule et al disclosed wherein the promoter is a constitutive promoter, e.g. CMV promoter [0047].
Barton disclosed wherein the promoter is a constitutive promoter, e.g. CMV promoter (pg 5, line 33).
With respect to Claim 36, Alberini et al is considered relevant prior art for having disclosed expression vectors, including viral vectors, e.g. retroviral vectors [0171], comprising a nucleic acid molecule encoding IGF-1 preproprotein, isoform 2 (SEQ ID NO:8) [0069, 105-106], wherein SEQ ID NO:8 is 100% identical to instant SEQ ID NO:23.
With respect to Claim 37, Kingsman et al disclosed a pharmaceutical comprising a therapeutically effective amount of a gene construct and/or a vector, together with one or more pharmaceutically acceptable excipients or vehicles (pg 45, ¶2-4).
Scheule et al disclosed a pharmaceutical comprising a therapeutically effective amount of a gene construct and/or a vector, together with one or more pharmaceutically acceptable excipients or vehicles [0083].
Barton disclosed a pharmaceutical comprising a therapeutically effective amount of a gene construct and/or a vector, together with one or more pharmaceutically acceptable excipients or vehicles (pg 24, lines 1-20).
Xie et al taught a pharmaceutical comprising a therapeutically effective amount of a gene construct and/or a vector, together with one or more pharmaceutically acceptable excipients or vehicles (pg 533, col. 2, Methods).
The cited prior art meets the criteria set forth in both Graham and KSR, and the teachings of the cited prior art provide the requisite teachings and motivations with a clear, reasonable expectation of success. Thus, the invention as a whole is prima facie obvious.
Response to Arguments
Applicant argues that Kingsman et al is directed to a lentiviral construct, not an rAAV.
Applicant’s argument(s) has been fully considered, but is not persuasive. In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). Xie et al, Barton et al, and Scheule et al taught/disclosed rAAV vectors.
As discussed in prior Office Actions, one of ordinary skill in the art has long-recognized, at least a decade(!) before the effective filing date of the instant application, the ability to produce an AAV vector encoding the artisan’s transgene of interest, including an IGF-1 transgene.
Applicant argues that Alberini et al do not teach rAAV vectors.
Applicant’s argument(s) has been fully considered, but is not persuasive. In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). Xie et al, Barton et al, and Scheule et al taught/disclosed rAAV vectors.
As discussed in prior Office Actions, one of ordinary skill in the art has long-recognized, at least a decade(!) before the effective filing date of the instant application, the ability to produce an AAV vector encoding the artisan’s transgene of interest, including an IGF-1 transgene.
Applicant argues that the lentiviral construct of Kingsman et al was not effective for encoding IGF-1.
Applicant’s argument(s) has been fully considered, but is not persuasive. Applicant fails to point with particularity where Kingsman et al disclose such a result. Rather, Kingsman et al clearly disclosed the vector to encode and express IGF-1 (e.g. pg 44, para 2-3; claim 11).
Applicant argues that Kazparzak et al does not give any guidance to the effectiveness of AAV vectors.
Applicant’s argument(s) has been fully considered, but is not persuasive. Kazparzak et al is not required to do as Applicant seeks.
In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). Xie et al, Barton et al, and Scheule et al taught/disclosed rAAV vectors.
Applicant argues that Scheule et al do not disclose an AAV8 capsid serotype.
Applicant’s argument(s) has been fully considered, but is not persuasive. Scheule et al disclosed the AAV vectors may have an AAV8 capsid serotype (e.g. [0067-68]).
2. Claims 33-34, 37-38, and 45-46 are rejected under AIA 35 U.S.C. 103 as being unpatentable over Kingsman et al (WO 08/071959; of record in IDS) in view of Kelly et al (2009; of record in IDS), Xie et al (2011; of record in IDS), Scheule et al (U.S. 2010/0216709; of record), Barton (WO 14/012025; of record in IDS), Kasprzak et al (2013; of record), and Alberini et al (US20030166555; of record), as applied to Claims 18, 31-33, and 36-37 above, and in further view of Anguela Martinez et al (WO 11/004051; English language equivalent U.S. 2014/0045923; both of record in IDS).
Determining the scope and contents of the prior art, and Ascertaining the differences between the prior art and the claims at issue.
With respect to Claims 33-34, Kingsman et al disclosed wherein the promoter is a constitutive promoter, e.g. CMV promoter (pg 14, ¶3).
Scheule et al disclosed wherein the promoter is a constitutive promoter, e.g. CMV promoter [0047].
Barton disclosed wherein the promoter is a constitutive promoter, e.g. CMV promoter (pg 5, line 33).
Neither Kingsman et al, Scheule et al, nor Barton disclose wherein the constitutive promoter is a CAG promoter.
However, before the effective filing date of the instantly claimed invention, and with respect to Claims 34 and 38, Anguela Martinez et al is considered relevant prior art for having disclosed a vector for the treatment of diabetes, said vector encoding a constitutive promoter operably linked to a nucleotide sequence encoding an IGF-1 protein, wherein the promoter may be a CMV promoter or a CAG promoter (WO ‘051, pg 4, lines 15-19; ‘923, [0011]).
Anguela Martinez et al disclosed the vector may be an AAV vector.
Considering objective evidence present in the application indicating obviousness or nonobviousness.
The focus when making a determination of obviousness should be on what a person of ordinary skill in the pertinent art would have known at the time of the invention, and on what such a person would have reasonably expected to have been able to do in view of that knowledge. This is so regardless of whether the source of that knowledge and ability was documentary prior art, general knowledge in the art, or common sense. M.P.E.P. §2141.
The rationale to modify or combine the prior art does not have to be expressly stated in the prior art; the rationale may be expressly or impliedly contained in the prior art or it may be reasoned from knowledge generally available to one of ordinary skill in the art, established scientific principles, or legal precedent established by prior case law. In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988); In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992). See also In re Kotzab, 217 F.3d 1365, 1370, 55 USPQ2d 1313, 1317 (Fed. Cir. 2000) (setting forth test for implicit teachings); In re Eli Lilly & Co., 902 F.2d 943, 14 USPQ2d 1741 (Fed. Cir. 1990) (discussion of reliance on legal precedent); In re Nilssen, 851 F.2d 1401, 1403, 7 USPQ2d 1500, 1502 (Fed. Cir. 1988) (references do not have to explicitly suggest combining teachings); and Ex parte Levengood, 28 USPQ2d 1300 (Bd. Pat. App. & Inter. 1993) (reliance on logic and sound scientific reasoning). See MPEP §2144.
Prior to the effective filing date of the instantly claimed invention, it would have been obvious to one of ordinary skill in the art to substitute a first constitutive promoter, e.g. a CMV promoter, as disclosed by Kingsman et al, Scheule et al, and Barton et al, with a second constitutive promoter, i.e. a CAG promoter, as disclosed by Anguela Martinez et al, with a reasonable expectation of success because the simple substitution of one known element for another would have yielded predictable results to one of ordinary skill in the art at the time of the invention. M.P.E.P. §2144.07 states "The selection of a known material based on its suitability for its intended use supported a prima facie obviousness determination in Sinclair & Carroll Co. v. Interchemical Corp., 325 U.S. 327, 65 USPQ 297 (1945).” “Reading a list and selecting a known compound to meet known requirements is no more ingenious than selecting the last piece to put in the last opening in a jig-saw puzzle." 325 U.S. at 335, 65 USPQ at 301.).” When substituting equivalents known in the prior art for the same purpose, an express suggestion to substitute one equivalent component or process for another is not necessary to render such substitution obvious. In re Fout, 675 F.2d 297, 213 USPQ 532 (CCPA 1982). M.P.E.P. §2144.06. An artisan would be motivated to substitute a first constitutive promoter, e.g. a CMV promoter, with a second constitutive promoter, i.e. a CAG promoter, because Anguela Martinez et al disclosed that the constitutive promoter may be a CMV promoter or a CAG promoter.
It is proper to "take account of the inferences and creative steps that a person of ordinary skill in the art would employ." KSR Int'l Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741,82 USPQ2d 1385, 1396 (2007). See also Id. At 1742, 82 USPQ2d 1397 ("A person of ordinary skill is also a person of ordinary creativity, not an automaton.").
It should be noted that the KSR case forecloses the argument that a specific teaching, suggestion, or motivation is required to support a finding of obviousness. See the recent Board decision Ex parte Smith, —USPQ2d—, slip op. at 20, (Bd. Pat. App. & Interf. June 25, 2007) (citing KSR, 82 USPQ2d at 1396) (available at http: www. uspto.gov/web/offices/dcom/bpai/prec/fd071925 .pdf).
With respect to Claims 18 and 38, Scheule et al disclosed the AAV may be of serotype 8 [0067].
Xie et al taught wherein the AAV is an AAV9 serotype (e.g. pg 533, col. 2, Methods, “AAV9 vectors”).
Anguela Martinez et al disclosed the AAV vector may be of serotype 8 (WO ‘051, pg 8, line 34; ‘923, [0029]).
With respect to Claims 31-32 and 45-46, Kingsman et al disclosed the miR target may be a miR-1 target site (e.g. pg 6, para 3), and as many as four copies of a miR target sequence are cloned into the gene construct (pg 50, Example 2).
Xie et al successfully reduced to practice engineering a rAAV expression vector to comprise both miR-1 and miR-122 target sites into an rAAV vector (e.g. Figure 2c, three miR-1 binding sites and three miR-122 binding sites).
In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). It is routine procedure to optimize component amounts to arrive at an optimal product that is superior for its intended use, since it has been held where the general conditions of a claim are disclosed in the prior art, discovering the optimum or workable ranges involves only routine skill in the art. Similarly, a prima facie case of obviousness exists where the claimed ranges or amounts do not overlap with the prior art but are close enough that one skilled in the art would have expected them to have the same properties. See M.P.E.P. §2144.05(I).
With respect to Claim 37, Kingsman et al disclosed a pharmaceutical comprising a therapeutically effective amount of a gene construct and/or a vector, together with one or more pharmaceutically acceptable excipients or vehicles (pg 45, ¶2-4).
Scheule et al disclosed a pharmaceutical comprising a therapeutically effective amount of a gene construct and/or a vector, together with one or more pharmaceutically acceptable excipients or vehicles [0083].
Barton disclosed a pharmaceutical comprising a therapeutically effective amount of a gene construct and/or a vector, together with one or more pharmaceutically acceptable excipients or vehicles (pg 24, lines 1-20).
Xie et al taught a pharmaceutical comprising a therapeutically effective amount of a gene construct and/or a vector, together with one or more pharmaceutically acceptable excipients or vehicles (pg 533, col. 2, Methods).
Anguela Martinez et al disclosed a pharmaceutical comprising a therapeutically effective amount of a gene construct and/or a vector, together with one or more pharmaceutically acceptable excipients or vehicles (WO ‘051, pg 9, line 10; ‘923, [0019, 30]).
The cited prior art meets the criteria set forth in both Graham and KSR, and the teachings of the cited prior art provide the requisite teachings and motivations with a clear, reasonable expectation of success. Thus, absent evidence to the contrary, the invention as a whole is prima facie obvious.
Response to Amendment
Applicant does not contest that prior to the effective filing date of the instantly claimed invention, it would have been obvious to one of ordinary skill in the art to substitute a first constitutive promoter, e.g. a CMV promoter, as disclosed by Kingsman et al, Scheule et al, and Barton et al, with a second constitutive promoter, i.e. a CAG promoter, as disclosed by Anguela Martinez et al, with a reasonable expectation of success because the simple substitution of one known element for another would have yielded predictable results to one of ordinary skill in the art at the time of the invention. M.P.E.P. §2144.07 states "The selection of a known material based on its suitability for its intended use supported a prima facie obviousness determination in Sinclair & Carroll Co. v. Interchemical Corp., 325 U.S. 327, 65 USPQ 297 (1945).” “Reading a list and selecting a known compound to meet known requirements is no more ingenious than selecting the last piece to put in the last opening in a jig-saw puzzle." 325 U.S. at 335, 65 USPQ at 301.).” When substituting equivalents known in the prior art for the same purpose, an express suggestion to substitute one equivalent component or process for another is not necessary to render such substitution obvious. In re Fout, 675 F.2d 297, 213 USPQ 532 (CCPA 1982). M.P.E.P. §2144.06. An artisan would be motivated to substitute a first constitutive promoter, e.g. a CMV promoter, with a second constitutive promoter, i.e. a CAG promoter, because Anguela Martinez et al disclosed that the constitutive promoter may be a CMV promoter or a CAG promoter.
3. Claims 30 and 44 are rejected under AIA 35 U.S.C. 103 as being unpatentable over Kingsman et al (WO 08/071959; of record in IDS) in view of Kelly et al (2009; of record in IDS), Xie et al (2011; of record in IDS), Scheule et al (U.S. 2010/0216709; of record), Barton (WO 14/012025; of record in IDS), Kasprzak et al (2013; of record), and Alberini et al (US20030166555; of record), as applied to Claims 18, 31-33, and 36-37 above, and in further view of Lagos-Quintana et al (2002; of record in IDS).
Determining the scope and contents of the prior art, and Ascertaining the differences between the prior art and the claims at issue.
Kelly et al taught that target elements to multiple miRNAs engineered within a single vector can increase gene silencing in multiple tissues (pg 411, col. 1), whereby miR-122a target sites are useful to inhibit expression in the liver and miR-1, miR-133, or miR-206 target sites, as per Kingsman et al, are useful to inhibit expression in the heart (Table 1).
Xie et al introduced miR-1 and/or miR-122 target sites into an rAAV vector (e.g. pg 527, col. 1, “complementary sites for miR-1, miR-122, or both were engineered…”).
Xie et al taught the miR-122 target site (Figure 4a; lower line) comprises a nucleotide sequence identical to nucleotides 1-22 of instant SEQ ID NO:8 (upper line), as shown below of:
1 CAAACACCATTGTCACACTCCA 22
||||||||||||||||||||||
ACAAACACCATTGTCACACTCCA
Neither Kingsman et al, Kelley et al, nor Xie et al teach/disclose wherein the gene construct comprises at least one target sequence of miRNA-122a consisting of the nucleotide sequence of SEQ ID NO:8.
However, before the effective filing date of the instantly claimed invention, and with respect to Claim 30, Lagos-Quintana et al is considered relevant prior art for having taught three art-recognized target sequences of miR-122 (SEQ ID NO:8), whereby the SEQ ID NO:8 sequence is shared by all miR-122 target sequences. Lagos-Quintana et al also taught three art-recognized target sequences of miR-1 (SEQ ID NO:15), whereby 21 of the 22 nucleotides of the SEQ ID NO:15 sequence is shared by all miR-1 target sequences.
MiR-122 target sequence [SEQ ID NO:8]
miR-122a: 5’- tcaaacaccattgtcacactcca -3’
miR-122b: 5’- acaaacaccattgtcacactcca -3’
miR-122a,b: 5’- .caaacaccattgtcacactcca -3’
Considering objective evidence present in the application indicating obviousness or nonobviousness.
The focus when making a determination of obviousness should be on what a person of ordinary skill in the pertinent art would have known at the time of the invention, and on what such a person would have reasonably expected to have been able to do in view of that knowledge. This is so regardless of whether the source of that knowledge and ability was documentary prior art, general knowledge in the art, or common sense. M.P.E.P. §2141.
The rationale to modify or combine the prior art does not have to be expressly stated in the prior art; the rationale may be expressly or impliedly contained in the prior art or it may be reasoned from knowledge generally available to one of ordinary skill in the art, established scientific principles, or legal precedent established by prior case law. In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988); In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992). See also In re Kotzab, 217 F.3d 1365, 1370, 55 USPQ2d 1313, 1317 (Fed. Cir. 2000) (setting forth test for implicit teachings); In re Eli Lilly & Co., 902 F.2d 943, 14 USPQ2d 1741 (Fed. Cir. 1990) (discussion of reliance on legal precedent); In re Nilssen, 851 F.2d 1401, 1403, 7 USPQ2d 1500, 1502 (Fed. Cir. 1988) (references do not have to explicitly suggest combining teachings); and Ex parte Levengood, 28 USPQ2d 1300 (Bd. Pat. App. & Inter. 1993) (reliance on logic and sound scientific reasoning). See MPEP §2144.
Prior to the effective filing date of the instantly claimed invention, it would have been obvious to one of ordinary skill in the art to substitute a first miR-122 target sequence comprising SEQ ID NO:8, as taught by Xie et al, with a second miR-122 target sequence, i.e. a miR-122a target sequence consisting of SEQ ID NO:8, as taught by Lagos-Quintana et al, with a reasonable expectation of success because the simple substitution of one known element for another would have yielded predictable results to one of ordinary skill in the art at the time of the invention. M.P.E.P. §2144.07 states "The selection of a known material based on its suitability for its intended use supported a prima facie obviousness determination in Sinclair & Carroll Co. v. Interchemical Corp., 325 U.S. 327, 65 USPQ 297 (1945).” “Reading a list and selecting a known compound to meet known requirements is no more ingenious than selecting the last piece to put in the last opening in a jig-saw puzzle." 325 U.S. at 335, 65 USPQ at 301.).” When substituting equivalents known in the prior art for the same purpose, an express suggestion to substitute one equivalent component or process for another is not necessary to render such substitution obvious. In re Fout, 675 F.2d 297, 213 USPQ 532 (CCPA 1982). M.P.E.P. §2144.06. It would have been obvious to one of ordinary skill in the art to choose from a finite number of identified, predictable options because “a person of ordinary skill has good reason to pursue the known options within his or her technical grasp. If this leads to the anticipate success, it is likely that product not of innovation but of ordinary skill and common sense.” The ordinary artisans previously recognized that there is a finite list of three known options of miR-122 target sequences.
The "mere existence of differences between the prior art and an invention does not establish the invention's nonobviousness." Dann v. Johnston, 425 U.S. 219, 230, 189 USPQ 257, 261 (1976). The gap between the prior art and the claimed invention may not be "so great as to render the [claim] nonobvious to one reasonably skilled in the art."Id
Instant specification fails to disclose an element of criticality for an art-recognized miR-122 target site sequence consisting of SEQ ID NO:8
CAAACACCATTGTCACACTCCA
as opposed to an art-recognized miR-122 target site sequence comprising SEQ ID NO:8, as taught by Xie et al
ACAAACACCATTGTCACACTCCA
It is proper to "take account of the inferences and creative steps that a person of ordinary skill in the art would employ." KSR Int'l Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741,82 USPQ2d 1385, 1396 (2007). See also Id. At 1742, 82 USPQ2d 1397 ("A person of ordinary skill is also a person of ordinary creativity, not an automaton.").
It should be noted that the KSR case forecloses the argument that a specific teaching, suggestion, or motivation is required to support a finding of obviousness. See the recent Board decision Ex parte Smith, —USPQ2d—, slip op. at 20, (Bd. Pat. App. & Interf. June 25, 2007) (citing KSR, 82 USPQ2d at 1396) (available at http: www. uspto.gov/web/offices/dcom/bpai/prec/fd071925 .pdf).
The cited prior art meets the criteria set forth in both Graham and KSR, and the teachings of the cited prior art provide the requisite teachings and motivations with a clear, reasonable expectation of success. Thus, absent evidence to the contrary, the invention as a whole is prima facie obvious.
Response to Amendment
Applicant does not contest that prior to the effective filing date of the instantly claimed invention, it would have been obvious to one of ordinary skill in the art to substitute a first miR-122 target sequence comprising SEQ ID NO:8, as taught by Xie et al, with a second miR-122 target sequence, i.e. a miR-122a target sequence consisting of SEQ ID NO:8, as taught by Lagos-Quintana et al, with a reasonable expectation of success because the simple substitution of one known element for another would have yielded predictable results to one of ordinary skill in the art at the time of the invention. M.P.E.P. §2144.07 states "The selection of a known material based on its suitability for its intended use supported a prima facie obviousness determination in Sinclair & Carroll Co. v. Interchemical Corp., 325 U.S. 327, 65 USPQ 297 (1945).” “Reading a list and selecting a known compound to meet known requirements is no more ingenious than selecting the last piece to put in the last opening in a jig-saw puzzle." 325 U.S. at 335, 65 USPQ at 301.).” When substituting equivalents known in the prior art for the same purpose, an express suggestion to substitute one equivalent component or process for another is not necessary to render such substitution obvious. In re Fout, 675 F.2d 297, 213 USPQ 532 (CCPA 1982). M.P.E.P. §2144.06. It would have been obvious to one of ordinary skill in the art to choose from a finite number of identified, predictable options because “a person of ordinary skill has good reason to pursue the known options within his or her technical grasp. If this leads to the anticipate success, it is likely that product not of innovation but of ordinary skill and common sense.” The ordinary artisans previously recognized that there is a finite list of three known options of miR-122 target sequences.
The "mere existence of differences between the prior art and an invention does not establish the invention's nonobviousness." Dann v. Johnston, 425 U.S. 219, 230, 189 USPQ 257, 261 (1976). The gap between the prior art and the claimed invention may not be "so great as to render the [claim] nonobvious to one reasonably skilled in the art."Id
Instant specification fails to disclose an element of criticality for an art-recognized miR-122 target site sequence consisting of SEQ ID NO:8
CAAACACCATTGTCACACTCCA
as opposed to an art-recognized miR-122 target site sequence comprising SEQ ID NO:8, as taught by Xie et al
ACAAACACCATTGTCACACTCCA
It is proper to "take account of the inferences and creative steps that a person of ordinary skill in the art would employ." KSR Int'l Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741,82 USPQ2d 1385, 1396 (2007). See also Id. At 1742, 82 USPQ2d 1397 ("A person of ordinary skill is also a person of ordinary creativity, not an automaton.").
4. Claims 18, 29, 33, 36, and 38 are rejected under AIA 35 U.S.C. 103 as being unpatentable over Kingsman et al (WO 08/071959; of record in IDS) in view of Kelly et al (2009; of record in IDS), Xie et al (2011; of record in IDS), Scheule et al (U.S. 2010/0216709; of record), Barton (WO 14/012025; of record in IDS), Kasprzak et al (2013; of record), and Alberini et al (US20030166555; of record), as applied to Claims 18, 31-33, and 36-37 above, and in further view of Monsonego (U.S. Patent 10,117,895; filed May 13, 2013; of record) and GenBank NM_001111284.1 (human IGF preproprotein, isoform 2; January 29, 2012; of record).
Determining the scope and contents of the prior art, and Ascertaining the differences between the prior art and the claims at issue.
Neither Kingsman et al, Scheule et al, Barton et al, nor Anguela-Martinez et al disclose wherein the polynucleotide encoding IGF-1 preproprotein, isoform 2, is SEQ ID NO:3 (7204 nucleotides in length).
However, before the effective filing date of the instantly claimed invention, and with respect to Claim 29, Monsonego is considered relevant prior art for having disclosed genetically modified T cells constitutively expressing a polypeptide of interest (e.g. col. 4, lines 9-10; col. 23, lines 35-38), wherein the polypeptide includes IGF-1 (e.g. col. 18), wherein the nucleotide sequence encoding IGF-1 is SEQ ID NO:52 (NM_001111284.1, col. 19, line 13), which is 100% identical to instant SEQ ID NO:3, as disclosed in the instant application (pg 15, lines 11-13; NM_001111284.1).
Considering objective evidence present in the application indicating obviousness or nonobviousness.
The focus when making a determination of obviousness should be on what a person of ordinary skill in the pertinent art would have known at the time of the invention, and on what such a person would have reasonably expected to have been able to do in view of that knowledge. This is so regardless of whether the source of that knowledge and ability was documentary prior art, general knowledge in the art, or common sense. M.P.E.P. §2141.
The rationale to modify or combine the prior art does not have to be expressly stated in the prior art; the rationale may be expressly or impliedly contained in the prior art or it may be reasoned from knowledge generally available to one of ordinary skill in the art, established scientific principles, or legal precedent established by prior case law. In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988); In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992). See also In re Kotzab, 217 F.3d 1365, 1370, 55 USPQ2d 1313, 1317 (Fed. Cir. 2000) (setting forth test for implicit teachings); In re Eli Lilly & Co., 902 F.2d 943, 14 USPQ2d 1741 (Fed. Cir. 1990) (discussion of reliance on legal precedent); In re Nilssen, 851 F.2d 1401, 1403, 7 USPQ2d 1500, 1502 (Fed. Cir. 1988) (references do not have to explicitly suggest combining teachings); and Ex parte Levengood, 28 USPQ2d 1300 (Bd. Pat. App. & Inter. 1993) (reliance on logic and sound scientific reasoning). See MPEP §2144.
Prior to the effective filing date of the instantly claimed invention, it would have been obvious to one of ordinary skill in the art to substitute a first nucleic acid sequence encoding IGF-1, as disclosed by Kingsman et al, with a second nucleic acid sequence encoding IGF-1, to wit, SEQ ID NO:3, as disclosed by Monsonego and GenBank NM_001111284.1, with a reasonable expectation of success because the simple substitution of one known element for another would have yielded predictable results to one of ordinary skill in the art at the time of the invention. M.P.E.P. §2144.07 states "The selection of a known material based on its suitability for its intended use supported a prima facie obviousness determination in Sinclair & Carroll Co. v. Interchemical Corp., 325 U.S. 327, 65 USPQ 297 (1945).” “Reading a list and selecting a known compound to meet known requirements is no more ingenious than selecting the last piece to put in the last opening in a jig-saw puzzle." 325 U.S. at 335, 65 USPQ at 301.).” When substituting equivalents known in the prior art for the same purpose, an express suggestion to substitute one equivalent component or process for another is not necessary to render such substitution obvious. In re Fout, 675 F.2d 297, 213 USPQ 532 (CCPA 1982). M.P.E.P. §2144.06. An artisan would be motivated to substitute a first nucleic acid sequence encoding IGF-1 with a second nucleic acid sequence encoding IGF-1, to wit, SEQ ID NO:3, because those of ordinary skill in the art previously recognized the existence of SEQ ID NO:3 to encode IGF-1 and Monsonego et al disclosed the use of SEQ ID NO:3 in an expression vector to express IGF-1 in the artisan’s host cell of interest.
It is proper to "take account of the inferences and creative steps that a person of ordinary skill in the art would employ." KSR Int'l Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741,82 USPQ2d 1385, 1396 (2007). See also Id. At 1742, 82 USPQ2d 1397 ("A person of ordinary skill is also a person of ordinary creativity, not an automaton.").
It should be noted that the KSR case forecloses the argument that a specific teaching, suggestion, or motivation is required to support a finding of obviousness. See the recent Board decision Ex parte Smith, —USPQ2d—, slip op. at 20, (Bd. Pat. App. & Interf. June 25, 2007) (citing KSR, 82 USPQ2d at 1396) (available at http: www. uspto.gov/web/offices/dcom/bpai/prec/fd071925 .pdf).
With respect to Claim 36, Alberini et al is considered relevant prior art for having disclosed expression vectors, including viral vectors, e.g. retroviral vectors [0171], comprising a nucleic acid molecule encoding IGF-1 preproprotein, isoform 2 (SEQ ID NO:8) [0069, 105-106], wherein SEQ ID NO:8 is 100% identical to instant SEQ ID NO:23.
The instant specification discloses that NM_001111284 (syn. SEQ ID NO:3) inherently and naturally encodes SEQ ID NO:23 (e.g. pg 15, lines 11-13), and thus the IGF-1 nucleotide sequence of Monsonego (NM_001111284.1) necessarily encodes an IGF-1 amino acid sequence that is 100% identical to instant SEQ ID NO:23.
With respect to Claims 18 and 38, Kingsman et al disclosed wherein the vector is a viral vector, to wit, a retroviral vector (pg 9, ¶2) or a lentiviral vector (pg 11, ¶2).
Scheule et al disclosed wherein the vector is a viral vector, to wit, a retroviral vector, a lentiviral vector, or an adeno-associated viral vector [0046].
Barton disclosed wherein the vector is a viral vector, to wit, an adeno-associated viral vector (pg 5, lines 31-34).
Monsonego disclosed wherein the vector may be a retroviral vector, a lentiviral vector, or an adeno-associated viral vector (e.g. col. 25, lines 7-8; col 26, lines 1-10).
With respect to Claim 33, Kingsman et al disclosed wherein the promoter is a constitutive promoter, e.g. CMV promoter (pg 14, ¶3).
Scheule et al disclosed wherein the promoter is a constitutive promoter, e.g. CMV promoter [0047].
Barton disclosed wherein the promoter is a constitutive promoter, e.g. CMV promoter (pg 5, line 33).
Monsonego disclosed wherein the promoter is a constitutive promoter, e.g. CMV promoter (e.g. col. 24, lines 15-18, and 67, ‘pCMV’; col. 39, Example 9).
The cited prior art meets the criteria set forth in both Graham and KSR, and the teachings of the cited prior art provide the requisite teachings and motivations with a clear, reasonable expectation of success. Thus, absent evidence to the contrary, the invention as a whole is prima facie obvious.
Response to Arguments
Applicant does not contest that prior to the effective filing date of the instantly claimed invention, it would have been obvious to one of ordinary skill in the art to substitute a first nucleic acid sequence encoding IGF-1, as disclosed by Kingsman et al, with a second nucleic acid sequence encoding IGF-1, to wit, SEQ ID NO:3, as disclosed by Monsonego, with a reasonable expectation of success because the simple substitution of one known element for another would have yielded predictable results to one of ordinary skill in the art at the time of the invention. M.P.E.P. §2144.07 states "The selection of a known material based on its suitability for its intended use supported a prima facie obviousness determination in Sinclair & Carroll Co. v. Interchemical Corp., 325 U.S. 327, 65 USPQ 297 (1945).” “Reading a list and selecting a known compound to meet known requirements is no more ingenious than selecting the last piece to put in the last opening in a jig-saw puzzle." 325 U.S. at 335, 65 USPQ at 301.).” When substituting equivalents known in the prior art for the same purpose, an express suggestion to substitute one equivalent component or process for another is not necessary to render such substitution obvious. In re Fout, 675 F.2d 297, 213 USPQ 532 (CCPA 1982). M.P.E.P. §2144.06. An artisan would be motivated to substitute a first nucleic acid sequence encoding IGF-1 with a second nucleic acid sequence encoding IGF-1, to wit, SEQ ID NO:3, because those of ordinary skill in the art previously recognized the existence of SEQ ID NO:3 to encode IGF-1 and Monsonego et al disclose the use of SEQ ID NO:3 in an expression vector to express IGF-1 in the artisan’s host cell of interest.
Conclusion
5. No claims are allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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KEVIN K. HILL
Examiner
Art Unit 1638
/KEVIN K HILL/Primary Examiner, Art Unit 1638