DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Election/Restrictions
Claims 1-20 are pending. Applicant’s election of Group I (claims 1-11) and the species AAVrh74 in the reply filed 5/11/26 is acknowledged. Because Applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)). Claims 12-20 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention.
Examination on the merits commences on claims 1-11
Claim Rejections - 35 USC § 101
`35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefore, subject to the conditions and requirements of this title.
Claims 1 and 3 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception (i.e., a law of nature, a natural phenomenon, or an abstract idea) without significantly more. The claims are drawn to an oligonucleotide comprising a regulatory control element and a lipase A (LIPA) cDNA sequence. However, the claims do not include elements, when considered separately and in combination, that are sufficient to amount to significantly more than the judicial exceptions as outlined below.
Subject Matter Eligibility Test for Products and Processes: Claims 1 and 3.
Step 1 - Is the Claim to a Process, Machine, Manufacture or Composition of Matter? YES
Claims 1 and 3 are directed to an oligonucleotide comprising a regulatory control element and a lipase A (LIPA) cDNA sequence. Thus, the claims are directed to a statutory category (e.g., a product).
Step 2A, Prong One - Does the Claim Recite an Abstract Idea, Law of Nature, or Natural Phenomenon? YES
Natural phenomena have been identified by the courts by way of example, including products of nature. Claim 1 recites an oligonucleotide comprising a regulatory control element and a lipase A (LIPA) cDNA sequence and claim 3 further recites SEQ ID NO: 1 which is the WT coding sequence for LIPA, which is a product of nature. Natural products, products that are not “markedly different” than their naturally occurring counterpart are judicial exceptions. See MPEP 2016.04(b). The courts have identified polynucleotides as one such natural product that may not be markedly different from their counterpart, the human LIPA gene. MPEP 2106.04(c) outlines the markedly different analysis. The claimed polynucleotide with regulatory control element, a LIPA cDNA sequence, and SEQ ID NO: 1 exists complementary to the human LIPA gene. Hutchinson (Hutchinson, A., US-20190151420-A1) teaches a reference SEQ ID NO: 1 as the wild-type LIPA nucleotide coding sequence, where reference SEQ ID NO: 1 (claim 1) has 100% identity to instant SEQ ID NO: 1 and which is the known coding sequence for the wild-type human LIPA gene [0016] and is thus is complementary to the human WT LIPA gene.
Therefore, the claimed polynucleotide is not markedly different than its naturally occurring LIPA gene counterpart and constitutes a judicial exception.Step 2A, Prong Two - Does the Claim Recite Additional Elements that Integrate the Judicial Exception into a Practical Application? NO
The Supreme Court has long distinguished between principles themselves, which are not patent eligible, and the integration of those principles into practical applications, which are patent eligible. The phrase "integration into a practical application" requires an additional element or a combination of additional elements in the claim to apply, rely on, or use the judicial exception in a manner that imposes a meaningful limit on the judicial exception, such that it is more than a drafting effort designed to monopolize the exception. In this case, claims 1 and 3 do not recite any additional elements that would integrate the natural product into a practical application.
Step 2B - Does the Claim Recite Additional Elements that Amount to Significantly More than the Judicial Exception? NO
The Supreme Court has identified a number of considerations for determining whether a claim with additional elements amounts to "significantly more" than the judicial exception(s) itself. The claims as a whole are evaluated as to whether it amounts to significantly more than the recited exception, i.e., whether any additional element, or combination of additional elements, adds an inventive concept to the claim (MPEP 2106.05). In this case no additional elements are recited in claims 1 and 3. Therefore, the claims do not amount to something significantly more than the judicial exception.
Subject Matter Eligibility Test for Products and Processes – Dependent claims
Note that Claims 4-6 are not rejected under §101. Claims 4-6 are further limited by oligonucleotides containing engineered expression systems and thus are more than mere natural phenomenon. See the §103 rejections below for details on SEQ ID NO: 3 and SEQ ID NO: 4 and nucleotides 1853-3906 of SEQ ID NO: 4 as containing engineered expression systems.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim(s) 1, 2, 7, 9, 10, and 11 are rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by Esteves (Esteves, M., WO-2020072873-A1).
Regarding claim 1, Esteves teaches AAV encoding polynucleotides including regulatory control elements coding for CNS associated genes including the LIPA gene (lipase A) sequence (pg 39 line 29 and pg 22 line 16 and pg 30 line 25) used for the treatment diseases including lysosomal storage disorders (pg 32 line 10 and pg 38 line 20). Esteves teaches the rAAV comprising a promoter operably linked to a transgene wherein the transgene encodes a lysosomal storage protein (pg 32 line 10) and includes Wolman Disease (Acid Lipase Disease) (pg 37 line 23).
Regarding claim 2, Esteves teaches regulatory control elements including hybrid control elements and fragments of control elements and includes the CMV promoter and fragments of the CMV promoters including minimal promoters inside hybrid control elements (pg 30 line 23-pg 31 line 25) and where the rAAVs comprise a CMV element or a portion thereof (pg 31 line 19).
Regarding claims 7, 9, and 10, Esteves teaches the polynucleotide compositions within rAAV adenoviral delivery constructs (claim 1).
Regarding claim 11, Esteves teaches the compositions are formulated for intravenous delivery administration (pg 41 line 24).
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claim(s) 3 is/are rejected under 35 U.S.C. 103 as being unpatentable over Esteves (Esteves, M., WO-2020072873-A1), as applied to claim 1, in view of Hutchinson (Hutchinson, A., US-20190151420-A1).
The teachings of Esteves applied above to claim 1 are incorporated here.
Regarding claim 3, Esteves does not teach LIPA cDNA comprises a nucleotide sequence at least 95% identical to instant SEQ ID NO: 1.
Hutchinson teaches mutations in the nucleotide sequence of a human LIPA gene associated with reduced lysosomal acid lipase (LAL) activity [0006]. Hutchinson teaches a method for treating a patient afflicted with or suspected of being afflicted with the lysosomal storage disease LAL-D comprising administering a therapeutically effective amount of a recombinant human gene with nucleotide sequence containing portions of the LIPA gene, i.e. SEQ ID NO: 1 where the wild-type LIPA nucleotide coding sequence, reference SEQ ID NO: 1 (claim 1) has 100% identity to instant SEQ ID NO: 1 and which is the known coding sequence for the wild-type human LIPA gene [0016].
It would have been obvious to one skilled in the art before the effective filing date of the claimed invention to have modified Esteves’ LIPA cDNA rAAV gene delivery construct which treats lysosomal storage diseases affected by the LAL gene to have delivered the WT LIPA gene sequence of SEQ ID NO: 1 taught by Hutchinson in an rAAV delivery construct. It would have merely amounted to a simple combination of prior art elements according to known methods to yield predictable results. The skilled artisan would have had a reasonable expectation that the SEQ ID NO: 1 sequence utilized within the rAAV gene delivery construct would predictably treat lysosomal storage diseases because Esteves employs rAAV LIPA gene delivery for therapeutic treatment and Hutchinson established SEQ ID NO: 1 as the WT known LIPA gene for which fragments of as delivered within a similar rAAV delivery construct were effective at treating LAL related disorders. The skilled artisan would therefore be motivated to employ the full LIPA gene sequence of SEQ ID NO: 1 in Esteves’ method of LAL related gene disorders to enhance therapeutic effectiveness.
Claim(s) 4 is/are rejected under 35 U.S.C. 103 as being unpatentable over Esteves (Esteves, M., WO-2020072873-A1), as applied to claim 1, in view of Hutchinson (Hutchinson, A., US-20190151420-A1) as applied to claim 3, and in further view of Mclaughlin (Mclaughlin, K.J., WO-2018093954-A1).
The teachings of Esteves and Hutchinson applied above to claim 1 and 3 are incorporated here.
Regarding claim 4, Esteves does not teach the LIPA cDNA containing delivery polynucleotide comprises a nucleotide sequence of SEQ ID NO: 3.
Mclaughlin teaches a recombinant expression system that enables delivery of clustered regularly interspaced short palindromic repeats (CRISPR)-based gene editing tools to the mitochondrion [0005]. Mclaughlin teaches the expression vector comprises all or part of the nucleotide sequence of SEQ ID NO: 9 [0144], which has 100% identity to the sequence of instant SEQ ID NO: 3.
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It would have been obvious to one skilled in the art before the effective filing date of the claimed invention to have modified Esteves’ LIPA cDNA gene delivery construct which treats lysosomal storage diseases affected by the LAL gene to have included Mclaughlin’s SEQ ID NO: 9 vector components. It would have merely amounted to a simple combination of prior art elements according to known methods to yield predictable results. The skilled artisan would have had a reasonable expectation that reference SEQ ID NO: 9 would be effective in a gene delivery construct because Mclaughlin teaches this vector sequence effectively employed to deliver genetic material to targeted regions. The skilled artisan would therefore be motivated to employ Mclaughlin’s vector sequence identical to claimed SEQ ID NO: 3 in Esteves’ modified method of rAAV LIPA gene deliver to treat LAL related gene disorders for enhanced therapeutic effectiveness.
Claim(s) 5, 6, and 8 is/are rejected under 35 U.S.C. 103 as being unpatentable over Esteves (Esteves, M., WO-2020072873-A1), as applied to claim 1, in view of Hutchinson (Hutchinson, A., US-20190151420-A1) as applied to claim 3, and in further view of Kotin (Kotin, R., US 20190000940 A1).
The teachings of Esteves and Hutchinson applied above to claim 1 and 3 are incorporated here.
Regarding claims 5 and 6, although Esteves and Hutchinson do not teach a polynucleotide 95% identical to instant SEQ ID NO: 4, the instant Specification (page 25, table 2) outlines SEQ ID NO: 4 components: plasmid r(sc) AAVrh74.miniCMV.LIPA such that it would have been obvious to combine the claimed known components (Specification Table 2, below) of SEQ ID NO: 4 with a LIPA transcript variant component of SEQ ID NO: 4, given SEQ ID NO: 4 LIPA transcript variant 1 component (position 2254-3453, 1200 bases) is 100% identical to the 1200 bases of known WT LIPA transcript SEQ ID NO: 1 disclosed by Hutchinson.
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Regarding the remaining components of instant SEQ ID NO: 4, Kotin teaches, in a similar method of rAAV gene delivery, the incorporation of known features for rAAV gene delivery such as: Kanamycin resistance gene [0150], origin of replication [0113], lacZ reporter [0152], CMV promoter fragments [0234, 0017]], 5′ and 3′ ITR [0017], SV40 poly(A) tail (AAV2-CMV-hGH intron-hAADC-SV40 poly(A) vector) [0223], and the elected AAVrh.74 serotype [0016].
Therefore, it would have been obvious to one skilled in the art before the effective filing date of the claimed invention to have further modified Esteves’ LIPA cDNA gene delivery construct which treats lysosomal storage diseases affected by the LAL gene to have also included SEQ ID NO: 4 components taught by Kotin and Hutchinson. It would have merely amounted to a simple combination of prior art elements according to known methods to yield predictable results. The skilled artisan would have had a reasonable expectation that components of SEQ ID NO: 4 would be effective at enhanced gene delivery because Hutchinson teaches SEQ ID NO: 1 which includes the exact LIPA transcript variant of instant SEQ ID NO: 4 and Kotin teaches the remaining components of SEQ ID NO: 4 employed within effective gene delivery constructs in a similar method. The skilled artisan would be motivated to combine the components of Esteves, Hutchinson, and Kotin such that a sequence of instant SEQ ID NO: 4 would be included in the LIPA gene delivery construct to treat LAL related gene disorders for enhanced therapeutic effectiveness.
Regarding 8, Kotin teaches the method constructs effectively employed within AAVrh74 serotype adenoviral vectors [0016 and 0069].
Conclusion
All claims are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JOHN CHARLES MCKILLOP whose telephone number is (703)756-1089. The examiner can normally be reached Mon-Fri 8:30-5:30.
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/JOHN CHARLES MCKILLOP/Examiner, Art Unit 1637
/EKATERINA POLIAKOVA-GEORGANTAS/Primary Examiner, Art Unit 1637
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