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 September 18, 2024.
Amendments
Applicant's response and amendments, filed September 18, 2024, is acknowledged. Applicant has cancelled Claims 1-29, and added new claims, Claims 30-44.
Claims 30-44 are pending and under consideration.
Priority
This application is a continuation of application 16/315,362, filed on January 4, 2019, now abandoned, which is a 371 of PCT/US2017/040735 filed on July 5, 2017. Applicant’s claim for the benefit of a prior-filed application provisional application 62/511,629 filed on May 26, 2017 and 62/358,541 filed on July 5, 2016 under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, or 365(c) is acknowledged.
The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of 35 U.S.C. 112(a) or the first paragraph of pre-AIA 35 U.S.C. 112, except for the best mode requirement. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994)
The disclosure of the prior-filed application, Application No. 62/358,541 filed on July 5, 2016 fails to provide adequate support or enablement in the manner provided by 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph for one or more claims of this application.
With respect to Claim 30, ‘541 fails to disclose the nucleic acid consisting of SEQ ID NO:2 flanked by rAAV ITRs.
Support for SEQ ID NO:2 may be found in 62/511,629 filed on May 26, 2017, e.g. claim 21.
With respect to Claims 31-32 and 37-38, ‘541 fails to disclose wherein one of the AAV ITRs is a mutant ITR, even more specifically, delta TRS ITR.
Support for SEQ ID NO:4 may be found in 62/511,629 filed on May 26, 2017, e.g. pg 14, lines 20-23).
With respect to Claims 34 and 40, ‘541 fails to disclose the SV40 promoter.
Support for SEQ ID NO:2 may be found in 62/511,629 filed on May 26, 2017, e.g. pg 16, line 30).
With respect to Claims 35 and 41, ‘541 fails to disclose the SV40 promoter nucleotide SEQ ID NO:4.
Support for SEQ ID NO:4 may be found in 62/511,629 filed on May 26, 2017, e.g. claim 24.
With respect to Claim 43, ‘541 fails to disclose the AAV2 capsid protein amino acid sequence SEQ ID NO:1.
Support for SEQ ID NO:2 may be found in 62/511,629 filed on May 26, 2017, e.g. pg 23, line 10).
Accordingly, the effective priority date of the instant claims is granted as May 26, 2017.
If applicant believes the earlier applications provide support for this disclosure, applicant should point out such support with particularity by page and line number in the reply to this Action.
Information Disclosure Statement
Applicant has filed an Information Disclosure Statement on September 18, 2024 that has been considered.
The signed and initialed PTO Forms 1449 are mailed with this action.
Specification
1. The disclosure is objected to because of the following informalities: the specification discloses “CB6” (e.g. Example 2), which appears to be Applicant’s lexicography for a promoter. However, the specification fails to disclose the identity of “CB6”.
Appropriate correction is required.
Claim Objections
2. Claims 32 and 38 are objected to because of the following informalities:
The claims recite “delta.TRS”. The abbreviation or acronym should be spelled out in the first appearance of the claims and should be followed by the abbreviation in parentheses.
Appropriate correction is required.
See, for example, Claim 30, “adeno-associated virus (AAV) and/or inverted terminal repeats (ITRs).
3. Claims 33 and 39 are objected to because of the following informalities:
The claims recite “CB6”. The abbreviation or acronym should be spelled out in the first appearance of the claims and should be followed by the abbreviation in parentheses.
Appropriate correction is required.
See, for example, Claim 30, “adeno-associated virus (AAV)” and/or “inverted terminal repeats (ITRs)”.
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.
4. Claims 33 and 39 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.
The claims recite “CB6” without first providing the complete name.
Where applicant acts as his or her own lexicographer to specifically define a term of a claim contrary to its ordinary meaning, the written description must clearly redefine the claim term and set forth the uncommon definition so as to put one reasonably skilled in the art on notice that the applicant intended to so redefine that claim term. Process Control Corp. v. HydReclaim Corp., 190 F.3d 1350, 1357, 52 USPQ2d 1029, 1033 (Fed. Cir. 1999). The term is indefinite because the specification does not clearly (re)define the term.
Morris et al (The Myeloid Zinc Finger Gene, MZF-l, Regulates the CD34 Promoter In Vitro, Blood 86(10): 3640-3647, 1995) is considered relevant prior art for having taught an expression vector identified using laboratory lexicography “CB6”, wherein the artisan’s cDNA of interest is operably linked to a CMV IE promoter (e.g. pg 3641, col. 1).
Gao et al (U.S. 2013/0281516) is considered relevant prior art for having disclosed rAAV expression vectors, wherein the artisan’s transgene of interest is operably linked to a CMV “CB” promoter comprising a CMV enhancer (e.g. Figure 1).
It appears that different artisans use different laboratory lexicography to describe/attribute the same transcriptional regulatory sequence.
The instant claims as a whole do not apprise one of ordinary skill in the art of its scope and, therefore, does not serve the notice function required by 35 U.S.C. 112, second paragraph, by providing clear warning to others as to what constitutes infringement of the patent.
5. Claims 35, 41, and 43 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.
See Office Action mailed August 4, 2023 (pg 4, item 3) in parent application 16/315,362.
As a first matter, a broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, the claims recite the broad recitation “the sequence set forth in”, and the claim also recites “SEQ ID NO”, which is the narrower statement of the range/limitation. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
As a second matter, the claims recite the phrases “the sequence set forth in” which renders the claims indefinite because the reference SEQ ID NO’s are each composed of a plurality of amino acid or nucleotide sequences or subsequences, respectively, and it is unclear to which sequence or subsequence “set forth in” the reference SEQ ID NO Applicant refers.
The preposition “in”, per “set forth in” does not have the same meaning as the preposition “of”. For example, “in” indicates a location or position within a limit or reference, e.g. a fragment or some portion of the referenced SEQ ID NO.
The house is in Tippecanoe county.
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Three cows are grazing in the field.
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The preposition “of” indicates possession of the reference, characteristic, or trait, that is to say, the entirety of the referenced SEQ ID NO.
The instant claims as a whole do not apprise one of ordinary skill in the art of its scope and, therefore, does not serve the notice function required by 35 U.S.C. 112, second paragraph, by providing clear warning to others as to what constitutes infringement of the patent.
The Examiner suggests amending the claims to instead recite “the sequence of SEQ ID NO”.
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.
6. Claims 30, 33, 36, 39, 42, and 44 are rejected under AIA 35 U.S.C. 103 as being unpatentable over Krishnan et al (June 2015; Applicant’s own work; of record in 16/315362 and IDS) in view of Schneider et al (1998; of record in 16/315362 and IDS), Tyckocinski (U.S. 2015/0353642; of record in 16/315362 and IDS), GenBank 4MSV_A (2014; of record in 16/315362 and IDS), and GenBank AY225406 (human FasL, 2003).
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 30, 36, and 42, Krishnan et al is considered relevant prior art for having taught an rAAV2 virus whose genome comprises a CB6 promoter operably linked to a sFasL transgene (e.g. Methods, mouse model, intravitreal injection of AAV2CB6.sFasL).
Those of ordinary skill in the art have long-recognized that the artisan’s transgene of interest is inherently and/or naturally flanked by the rAAV ITRs.
Krishnan et al do not teach wherein the sFasL polypeptide is encoded by a nucleic acid sequence consisting of SEQ ID NO:2.
Instant SEQ ID NO:2 encodes the sFasL amino acid sequence of SEQ ID NO:3, as shown below:
EKQIGHPSPPPEKKELRKVAHLTGKSNSRSMPLEWEDTYGIVLLSGVKYKKGGLVINETG
LYFVYSKVYFRGQSCNNLPLSHKVYMRNSKYPQDLVMMEGKMMSYCTTGQMWARSSYLGA
VFNLTSADHLYVNVSELSLVNFEESQTFFGLYKL*
However, prior to the effective filing date of the instantly claimed invention, and with respect to Claim(s) 30, Schneider et al is considered relevant prior art for having taught human FasL is naturally processed by proteolytic cleavage between amino acids 126^127, thereby generating soluble FasL consisting of amino acids 127-281 of full-length FasL (Figure 1c, ‘naturally processed sFasL’; lower line below), one amino acid longer than SEQ ID NO:3 (upper line), as shown below:
-EKQIGHPSPPPEKKELRKVAHLTGKSNSRSMPLEWEDTYGIVLLSGVKYKKGGLVINETGLY
LEKQIGHPSPPPEKKELRKVAHLTGKSNSRSMPLEWEDTYGIVLLSGVKYKKGGLVINETGLY
FVYSKVYFRGQSCNNLPLSHKVYMRNSKYPQDLVMMEGKMMSYCTTGQMWARSSYLGAVFNL
FVYSKVYFRGQSCNNLPLSHKVYMRNSKYPQDLVMMEGKMMSYCTTGQMWARSSYLGAVFNL
TSADHLYVNVSELSLVNFEESQTFFGLYKL
TSADHLYVNVSELSLVNFEESQTFFGLYKL
Similarly, Tyckocinski is considered relevant prior art for having disclosed the use of:
a soluble FasL amino acid sequence (SEQ ID NO:11) comprising N-terminal Leucine and SEQ ID NO:3 (e.g. [0108]), as per Schneider et al; or
a soluble FasL amino acid sequence (SEQ ID NO:12) consisting of SEQ ID NO:3 (e.g. [0109]).
Similarly, GenBank 4MSV_A is considered relevant prior art for having taught a recombinant sFasL fragment used to study the crystal structure of FasL and Dcr3 complex (per Liu et al; see cover page Accession Numbers 4MSV; Table 1, “PDB ID” 4MSV), wherein the FasL fragment (lower line) is composed of 152 amino acids and consists of amino acids 3-154 of SEQ ID NO:3 (upper line), as shown below:
EKQIGHPSPPPEKKELRKVAHLTGKSNSRSMPLEWEDTYGIVLLSGVKYKKGGLVINETGLY
--QIGHPSPPPEKKELRKVAHLTGKSNSRSMPLEWEDTYGIVLLSGVKYKKGGLVINETGLY
FVYSKVYFRGQSCNNLPLSHKVYMRNSKYPQDLVMMEGKMMSYCTTGQMWARSSYLGAVFNL
FVYSKVYFRGQSCNNLPLSHKVYMRNSKYPQDLVMMEGKMMSYCTTGQMWARSSYLGAVFNL
TSADHLYVNVSELSLVNFEESQTFFGLYKL
TSADHLYVNVSELSLVNFEESQTFFGLYKL
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).
The prior art taught/disclosed the use of sFasL whose N-terminal amino acids are:
i) LEKQIGHPSP…FFGLYKL (Schneider et al; Tyckocinski);
ii) EKQIGHPSP…FFGLYKL (instant SEQ ID NO:3, Tyckocinski); and
iii) --QIGHPSP…FFGLYKL (GenBank 4MSV_A).
Instant specification fails to disclose an element of criticality for the sFasL N-terminus of EKQIGHP…, as opposed to the sFasL N-terminus of LEKQIGHP… (+1 amino acid) and/or QIGHP… (-2 amino acids) taught/disclosed by the prior art.
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.
GenBank AY225406 is considered relevant prior art for having taught a nucleic acid sequence encoding human FasL, wherein nucleotides 382-846 are 100% identical to instant SEQ ID NO:2.
In light of GenBank AY225406, those of ordinary skill in the art would have recognized the sFasL-encoding nucleic acids of Schneider et al; Tyckocinski, and GenBank 4MSV_A, respectively (lower lines), relative to instant SEQ ID NO:2 (upper line, underlined), to be:
---GAGAAGCAAATAGGCCACCCCAGTCCACCCCCTGAAAAAAAGGAGCTGAGGAAAGT
TTGGAGAAGCAAATAGGCCACCCCAGTCCACCCCCTGAAAAAAAGGAGCTGAGGAAAGT
---GAGAAGCAAATAGGCCACCCCAGTCCACCCCCTGAAAAAAAGGAGCTGAGGAAAGT
---------CAAATAGGCCACCCCAGTCCACCCCCTGAAAAAAAGGAGCTGAGGAAAGT
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).
The prior art taught/disclosed the use of sFasL, which, in light of GenBank AY225406, would be encoded by the nucleotides:
i) TTGGAGAAGCAAA… (Schneider et al; Tyckocinski);
ii) ---GAGAAGCAAA… (instant SEQ ID NO:2, Tyckocinski); and
iii) ---------CAAA… (GenBank 4MSV_A).
Instant specification fails to disclose an element of criticality for the sFasL N-terminus of EKQIGHP…, as opposed to the sFasL N-terminus of LEKQIGHP… (+1 amino acid) and/or QIGHP… (-2 amino acids) taught/disclosed by the prior art.
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.
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 and gene therapy expression vectors. 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 sFasL amino acid sequence, as taught by Applicant (Krishnan et al) with a second sFasL amino acid sequence comprising the amino acid sequence of SEQ ID NO:3, encoded by the nucleic acid sequence of SEQ ID NO:2, in a recombinant AAV expression vector encoding and expressing a human sFasL protein 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 sFasL amino acid sequence with a second sFasL amino acid sequence comprising the amino acid sequence of SEQ ID NO:3, encoded by the nucleic acid sequence of SEQ ID NO:2, in a recombinant AAV expression vector encoding and expressing a human sFasL protein because those of ordinary skill in the art previously recognized and successfully reduced to practice expression of:
i) a sFasL amino acid sequence comprising 1 additional N-terminal amino acid relative to instant SEQ ID NO:3 (Schneider et al; Tyckocinski);
ii) a sFasL amino acid sequence consisting of instant SEQ ID NO:3 (Tyckocinski); and
iii) a sFasL amino acid sequence comprising 2 fewer N-terminal amino acids relative to instant SEQ ID NO:3 (GenBank 4MSV_A).
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.”
One of ordinary skill in the art would understand how to design rAAV expression vector nucleic acid molecules encoding sFasL, whereby the ordinary artisan could have pursued the known potential options with a reasonable expectation of success, per the decades-old, routine molecular biology reagents, long-practiced in the art, whereby the number of possible sFasL sequences from which to choose is neither astronomical nor insurmountable, and it would be only routine experimentation to determine which yields sFasL expression and activity.
As discussed above, 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).
The prior art taught/disclosed the use of sFasL whose N-terminal amino acids are:
i) LEKQIGHPSP…FFGLYKL (Schneider et al; Tyckocinski);
ii) EKQIGHPSP…FFGLYKL (instant SEQ ID NO:3, Tyckocinski); and
iii) --QIGHPSP…FFGLYKL (GenBank 4MSV_A).
In light of GenBank AY225406, those of ordinary skill in the art would have recognized the sFasL-encoding nucleic acids of Schneider et al; Tyckocinski, and GenBank 4MSV_A, respectively (lower lines), relative to instant SEQ ID NO:2 (upper line, underlined), to be:
---GAGAAGCAAATAGGCCACCCCAGTCCACCCCCTGAAAAAAAGGAGCTGAGGAAAGT
TTGGAGAAGCAAATAGGCCACCCCAGTCCACCCCCTGAAAAAAAGGAGCTGAGGAAAGT
---GAGAAGCAAATAGGCCACCCCAGTCCACCCCCTGAAAAAAAGGAGCTGAGGAAAGT
---------CAAATAGGCCACCCCAGTCCACCCCCTGAAAAAAAGGAGCTGAGGAAAGT
Instant specification fails to disclose an element of criticality for the sFasL N-terminus of EKQIGHP…, as opposed to the sFasL N-terminus of LEKQIGHP… (+1 amino acid) and/or QIGHP… (-2 amino acids) taught/disclosed by the prior art.
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.
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 33 and 39, Krishnan et al taught wherein the rAAV vector whose genome comprises a CB6 promoter operably linked to a sFasL transgene (e.g. Methods, mouse model, intravitreal injection of AAV2CB6.sFasL).
With respect to Claim 44, Krishnan et al taught wherein the rAAV is formulated with a pharmaceutically acceptable excipient (e.g. Methods, mouse model, intravitreal injection of AAV2CB6.sFasL), whereby those of ordinary skill in the art have long-recognized that administration of rAAV gene therapy vectors is routinely performed using pharmaceutically acceptable excipients.
Gao et al disclosed wherein the rAAV is formulated with a pharmaceutically acceptable excipient (e.g. [0093-94, 97-98]).
With respect to Claim 42, Krishnan et al taught wherein the rAAV comprises an AAV2 capsid (e.g. Methods, AAV2CB6.sFasL).
Gao et al disclosed wherein the rAAV comprises an AAV2 capsid (e.g. [0066, 146]).
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.
7. Claim 43 is rejected under AIA 35 U.S.C. 103 as being unpatentable over Krishnan et al (June 2015; Applicant’s own work; of record in 16/315362 and IDS) in view of Schneider et al (1998; of record in 16/315362 and IDS), Tyckocinski (U.S. 2015/0353642; of record in 16/315362 and IDS), GenBank 4MSV_A (2014; of record in 16/315362 and IDS), and GenBank AY225406 (human FasL, 2003), as applied to Claims 30, 33, 36, 39, 42, and 44 above, and in further view of Li et al (U.S. 2005/0112765).
Determining the scope and contents of the prior art, and Ascertaining the differences between the prior art and the claims at issue.
Applicant (Krishnan et al) previously taught an rAAV2 virus whose genome encodes and expresses a sFasL transgene.
Applicant did not teach wherein the AAV2 capsid comprises the amino acid sequence of SEQ ID NO:1.
However, prior to the effective filing date of the instantly claimed invention, and with respect to Claim(s) 43, Li et al is considered relevant prior art for having disclosed rAAV viruses comprising an AAV2 capsid, wherein the AAV2 capsid comprises the amino acid sequence (e.g. SEQ ID NO:9) that is 100% identical to instant SEQ ID NO: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 AAV2 capsid, as taught by Applicant, with a second AAV2 capsid whose amino acid sequence is 100% identical to instant SEQ ID NO:1, as disclosed by Li et al, in a recombinant AAV expression vector encoding and expressing a human sFasL protein 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).” 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 AAV2 capsid with a second AAV2 capsid whose amino acid sequence is 100% identical to instant SEQ ID NO:1 in a recombinant AAV expression vector encoding and expressing a human sFasL protein because those of ordinary skill in the art had long-recognized and successfully reduced to practice the ability to generate rAAV2 viruses encoding the artisan’s transgene of interest, wherein said rAAV2 virus comprises an AAV2 capsid amino acid sequence that is 100% identical to instant SEQ ID NO:1.
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, the invention as a whole is prima facie obvious.
8. Claims 31-35, 37-42, and 44 are rejected under AIA 35 U.S.C. 103 as being unpatentable over Krishnan et al (June 2015; Applicant’s own work; of record in 16/315362 and IDS) in view of Schneider et al (1998; of record in 16/315362 and IDS), Tyckocinski (U.S. 2015/0353642; of record in 16/315362 and IDS), GenBank 4MSV_A (2014; of record in 16/315362 and IDS), and GenBank AY225406 (human FasL, 2003), as applied to Claims 30, 33, 36, 39, 42, and 44 above, and in further view of Gao et al (U.S. 2013/0281516).
Determining the scope and contents of the prior art, and Ascertaining the differences between the prior art and the claims at issue.
Applicant (Krishnan et al) previously taught a rAAV2 expression vector whose genome comprises a sFasL-encoding nucleic acid operably linked to a CB6 promoter.
As discussed above, the Examiner interprets “CB6” to mean a CMV immediate-early (IE) promoter.
To the extent Applicant argues otherwise, see 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, above.
With respect to Claims 34-35 and 40-41, Gao et al is considered relevant prior art for having disclosed rAAV expression vectors, wherein the artisan’s transgene of interest is operably linked to a CMV “CB” promoter comprising a CMV enhancer (e.g. Figure 1) or an SV40 promoter (e.g. SEQ ID NO:14) comprising a nucleic acid sequence 100% identical to instant SEQ ID NO:4, as shown below:
TCTCCCCCCCCTCCCCACCCCCAATTTTGTATTTATTTATTTTTTAATTATTTTGTGCAG
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
TCTCCCCCCCCTCCCCACCCCCAATTTTGTATTTATTTATTTTTTAATTATTTTGTGCAG
CGATGGGGGCGGGGGGGGGGGGGGGGGGGGCGCGCGCCAGGCGGGGCGGGGCGGGGCGAG
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
CGATGGGGGCGGGGGGGGGGGGGGGGGGGGCGCGCGCCAGGCGGGGCGGGGCGGGGCGAG
GGGCGGGGCGGGGCGAGGCGGAGAGGTGCGGCGGCAGCCAATCAGAGCGGCGCGCTCCGA
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
GGGCGGGGCGGGGCGAGGCGGAGAGGTGCGGCGGCAGCCAATCAGAGCGGCGCGCTCCGA
AAGTTTCCTTTTATGGCGAGGCGGCGGCGGCGGCGGCCCTATAAAAAGCGAAGCGCGCGG
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
AAGTTTCCTTTTATGGCGAGGCGGCGGCGGCGGCGGCCCTATAAAAAGCGAAGCGCGCGG
CGGGCGGGAGCGGGATCAGCCACCGCGGTGGCGGCCCTAGAGTCGATCGAGGAACTGAAA
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
CGGGCGGGAGCGGGATCAGCCACCGCGGTGGCGGCCCTAGAGTCGATCGAGGAACTGAAA
AACCAGAAAGTTAACTGGTAAGTTTAGTCTTTTTGTCTTTTATTTCAGGTCCCGGATCC
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
AACCAGAAAGTTAACTGGTAAGTTTAGTCTTTTTGTCTTTTATTTCAGGTCCCGGATCC
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 promoter, e.g. a CB6 promoter of Krishnan et al, with a second promoter, i.e. an SV40 promoter comprising a nucleic acid sequence 100% identical to instant SEQ ID NO:4, in a recombinant AAV expression vector encoding and expressing a human sFasL protein 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).” 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 promoter, e.g. a CB6 promoter, with a second promoter, i.e. an SV40 promoter comprising a nucleic acid sequence 100% identical to instant SEQ ID NO:4, in a recombinant AAV expression vector encoding and expressing a human sFasL protein because Gao et al disclosed and successfully demonstrated the ability to synthesize rAAV expression vectors in which the artisan’s transgene of interest is operably linked to CMV/CB promoter or an SV40 promoter comprising a nucleic acid sequence 100% identical to instant SEQ ID NO:4.
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 33 and 39, Krishnan et al taught wherein the rAAV vector whose genome comprises a CB6 promoter operably linked to a sFasL transgene (e.g. Methods, mouse model, intravitreal injection of AAV2CB6.sFasL).
Gao et al disclosed rAAV expression vectors, wherein the artisan’s transgene of interest is operably linked to a CMV “CB” promoter comprising a CMV enhancer (e.g. Figure 1), which the Examiner interprets to read upon instant “CB6”.
To the extent Applicant argues otherwise, see 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, above.
With respect to Claims 31-32 and 37-38, Gao et al disclosed wherein at least one of the rAAV ITRs is a mutant ITR, more specifically, a delta.TRS ITR (e.g. [0006, 8]; pg 19, Construct A, SEQ ID NO:14)
With respect to Claim 44, Krishnan et al taught wherein the rAAV is formulated with a pharmaceutically acceptable excipient (e.g. Methods, mouse model, intravitreal injection of AAV2CB6.sFasL), whereby those of ordinary skill in the art have long-recognized that administration of rAAV gene therapy vectors is routinely performed using pharmaceutically acceptable excipients.
Gao et al disclosed wherein the rAAV is formulated with a pharmaceutically acceptable excipient (e.g. [0093-94, 97-98]).
With respect to Claim 42, Krishnan et al taught wherein the rAAV comprises an AAV2 capsid (e.g. Methods, AAV2CB6.sFasL).
Gao et al disclosed wherein the rAAV comprises an AAV2 capsid (e.g. [0066, 146]).
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.
Conclusion
9. No claims are allowed.
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KEVIN K. HILL
Examiner
Art Unit 1638
/KEVIN K HILL/Primary Examiner, Art Unit 1638
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