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
This action is in response to the papers filed on 12/30/2025. Claims 1-5, 7-16, 18-23 and 26-27 are currently pending as per claims filed on 08/21/2023.
Applicant’s election of Group I (Claims 1-5, 7-12, and 19-20) drawn to nucleic acid comprising an iduronate-2-sulfatase gene sequence and a repeat of the Apolipoprotein E (ApoEII) gene sequence in the reply filed on 12/30/2025 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)).
After further consideration, claims 21 and 27 are rejoined with Group I there being no undue search burden.
Claims 13-16, 18, 22-23, and 26 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a non-elected invention, there being no allowable generic or linking claim.
The requirement for restriction is still deemed proper and is therefore made FINAL.
Therefore, claims 1-5, 7-12, 19-21 and 27 are subject to examination to which the following grounds of rejection are applicable.
Priority
Acknowledgement is made to the applicants’ claim for benefit as a DIV of 16/484,311 filed 08/07/2019 (now US Patent 11701390). 16/484,311 is a 371 of PCT/GB18/50347 filed 02/07/2018.
The instant application is an improper divisional, and thus does not receive benefit of the ‘121 shield’ over the parent application 16/484,311. The claims presented are not consonant with the restriction requirement set forth in prior-filed application 16/484,311. Specifically, the claims filed with the instant application and the inventive group elected for examination are identical to those of the parent application 16/484,311 and are not patentably distinct from the claims of filed on 08/07/2019 for parent application 16/484,311.
Applicants are required to correct the priority claim of the instant application by filing a new ADS, wherein under “domestic priority” the word “divisional” is lined through and the word “continuation” is written in and underlined.
Specification
Cross-Reference to Related Application.
The disclosure filed on 08/21/2023 is objected to because the cross-reference to related application on the first page of the specification required to be updated with the now US Patent 11701390. Moreover, the disclosure filed on 08/21/2023 is objected to because this application should claim continuity from application 16/484,311 as a continuation and not a divisional.
Appropriate correction is required.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 08/21/2023 were filed before the mailing date of the non-final office action. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Sequence Compliance
This application is objected to because the amino acid sequences of Figure 1b are not associated with a sequence identifier (a SEQ ID NO) in either the figure or the figure legend. All sequences longer than ten nucleotides or four amino acids referenced in the specification must include a SEQ ID NO and must be included in the Sequence Listing. MPEP 2422.02 requires, "that when a sequence is presented in a drawing, regardless of the format or the manner of presentation of that sequence in the drawing, the sequence must still be included in the Sequence Listing and the sequence identifier ("SEQ ID NO:X') must be used, either in the drawing or in the Brief Description of the Drawings." See MPEP § 2421-2422. Applicant must amend the Drawings or the brief description of the Drawings on page 15 of the specification in response to this office action and must confirm that all sequences within the FIGs are in fact included in the sequence listing.
Required response – Applicant must provide:
Replacement and annotated drawings in accordance with 37 CFR 1.121(d) inserting the required sequence identifiers;
AND/OR
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required sequence identifiers into the Brief Description of the Drawings, consisting of:
A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
A copy of the amended specification without markings (clean version); and
A statement that the substitute specification contains no new matter.
Claim Interpretation
Claim 1 recites “A nucleic acid comprising an iduronate-2-sulfatase (IDS) gene sequence and a repeat of the Apolipoprotein E (ApoEII) gene sequence.” The abbreviation ApoEII is then recited in the dependent claims. Apolipoprotein E isoform 2 is a known isoform in the prior art. However, neither the specification nor the claims detail that the Apolipoprotein E described by the instant application and (the abbreviation ApoEII) refers to a specific isoform. Instead, Applicants describe that the abbreviation ApoEII is equivalent to Apolipoprotein E. Therefore, the claims as written will be interpreted as referring to Apolipoprotein E, typically abbreviated in the prior art as ApoE. Please also see 112b rejection below.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1-5, 7-12, 19-21 and 27 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.
Claim 1is indefinite due to the use of parentheticals. It is not clear whether the parenthetical is used to indicate a limitation, a preferred embodiment, or synonym, etc. Accordingly, the metes and bounds of the claim are not clear. Apolipoprotein E isoform 2 is a known isoform in the prior art. However, neither the specification nor the claims detail that the Apolipoprotein E described by the instant application refers to a specific isoform. Instead, they describe that the abbreviation ApoEII is equivalent to Apolipoprotein E. Therefore, the claim as written will be interpreted as referring to Apolipoprotein E. Applicant must amend plainly recite what the intended mean is for this claim. .
The phrase “a derivative sequence having at least 90% homology thereof” in line 3 of claim 5 is vague and renders the claim indefinite. It is unclear whether the “derivative sequence” is intended to be a partial sequence of a full-length sequence of SEQ ID No. 1 or 2. It is also unclear whether the phrase “at least 90% homology thereof” means it is at least 90% homology sequence having at least 95% homology thereof” in line 5 of claim 5 is also vague and renders the claim indefinite for the same reason stated above.
Claim 5 is indefinite in its recitation of the phrase “the sequence according to” in lines 2 and 4 because it is unclear if the phrase “the sequence according to” should be interpreted narrowly to encompass only materials that have a structure identical to the SEQ ID NO: or if the phrase should be interpreted broadly to encompass materials which have a structure “similar” to the SEQ ID NO:. The metes and bounds are not clearly set forth.
The phrase “a derivative sequence having at least 95% homology thereof” in line 3 of claim 7 is vague and renders the claim indefinite. It is unclear whether the “derivative sequence” is intended to be a partial sequence of a full-length sequence of SEQ ID No. 4. It is also unclear whether the phrase “at least 95% homology thereof” means it is at least 95% homology to a partial sequence or the full length sequence of SEQ ID No. 4.
Claim 7 is indefinite in its recitation of the phrase “the sequence according to” in line 2 because it is unclear if the phrase “the sequence according to” should be interpreted narrowly to encompass only materials that have a structure identical to the SEQ ID NO: or if the phrase should be interpreted broadly to encompass materials which have a structure “similar” to the SEQ ID NO:. The metes and bounds are not clearly set forth.
Claim 19 recites the limitation "the composition of claim 1" in line 1. There is insufficient antecedent basis for this limitation in the claim. Claim 19 depends from claim 1, which fails to recite any “composition”. Thus, the phrase "the composition of claim 1" in line 1 lacks antecedent basis. Claim 20 depends from claim 19.
Claims 11, 19 and 21 are vague and indefinite in its recitation of the phrase "for use in the treatment " in that the metes and bounds of the term " for use in the treatment " are unclear. It is unclear whether the claims 11, 19 and 21 encompass methods or products claims. Applicant appears to be attempting to claim both a composition and a use thereof, which is not statutory. The claims should be redrafted such that they particularly point out the components and, where necessary, the absolute amounts thereof within the composition. As such, the metes and bounds of the claims cannot be determined.
Claim 2 is vague and indefinite in the recitation of “…capable of…” , since this phrase refers to a latent ability, and it is unknown whether the ability is expressed or observed in the invention.
Note, it has been held that the recitation that an element is “capable of” performing a function is not a positive limitation, but only requires the ability to so perform. It does not constitute a limitation in any patentable sense. In re Hutchinson, 69 USPQ 138.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1, 4, 8-9, 11-12 and 19-20 are directed to a nucleic acid comprising an iduronate-2-sulfatase (IDS) gene sequence and a repeat of the apolipoprotein E (ApoEII) gene sequence. Claim 4 specifies the repeat of the ApoEII sequence is in the form of a tandem repeat. Claim 8 specifies the nucleic acid is incorporated in a gene therapy vector. Claim 9 specifies the vector is a lentiviral vector. Claim 11 specifies the nucleic acid is for use in the treatment, management, retardation of progression or normalization of development of a disease or condition attributable to induronate-2-sulfatase (IDS) deficiency. Claim 12 specifies the disease or condition comprises mucopolysaccharidosis type II (MPS II) or Hunters syndrome. Claim 19 specifies the composition for use in the treatment, management, retardation of progression or normalization of development of a disease or condition attributable to induronate-2-sulfatase (IDS) deficiency. Claim 20 specifies the disease or condition comprises mucopolysaccharidosis type II (MPS II) or Hunters syndrome.
Claims 1, 4, 8-9, 11-12 and 19-20 are rejected under 35 U.S.C. 103 as being unpatentable over Heller et al., 2016 (WO 2016/077356 A2, IDS filed 8/21/2023) in view of Wang et al., 2013 (PNAS, Vol. 110, No. 8, p. 2999-3004, IDS filed 8/21/2023).
Regarding claims 1, 4, 8-9, 11-12 and 19-20, Heller teaches a pharmaceutical composition comprising a blood brain barrier (BBB) peptide and a human peptide such as an iduronate-2-sulfatase protein (IDS) protein, and the use of the composition for treating MOS I disease (e.g. Abstract, p. 4, lines 21-23). The composition comprising a human protein (e.g. IDS) and a carrier peptide that facilitates the transport of the human protein across the BBB for treating MPS I (e.g. p. 4, lines 24-28). The BBB carrier peptide comprises a first portion comprising a transferrin-receptor binding site of a transferrin, or a receptor binding domain of an apolipoprotein, linked to a second portion comprising a hydrophilic segment of from 4-50 hydrophilic amino acids. The receptor-binding domain of an apolipoprotein can be from ApoE (ApoEII of the instant application), ApoE2, ApoE3 and ApoE4 (e.g. p. 4, lines 29-34). Heller also discloses a nucleic acid sequence encoding IDS can be molecularly cloned into a suitable vector for expression (e.g. p. 36, lines 23-26). Suitable expression vector includes AAV based vector, retrovirus based vector and plasmid vectors (e.g. p. 37, lines 11-14). The recombinant IDS used in the formulation can be produced in vitro using cultured host cells, which can be mammalian cells. The mammalian cells include human embryonic kidney 293 cells (HEK293), HeLa cells, mouse kidney cells, human liver cells, human lung cells, and human hepatoma line (Hep G2) (e.g. p. 37 line 15 to page 38 line 1).
Heller does not specifically teach a repeat (claim 1) or a tandem repeat (claim 4) of the ApoEII gene sequence (claim 1), or the vector is a lentiviral vector (claim 9).
Wang reports “Engineering a lysosomal enzyme with a derivative of receptor-binding domain of ApoE (ApoEII of the instant application) enables delivery across the blood-brain barrier” (e.g. Title). Wang identified two fusion candidates, IDUAe1 and IDUAe2, which exhibited desirable receptor-mediated binding, endocytosis and transendothelial transport as well as appropriate lysosomal enzyme trafficking and biological function (e.g. Abstract). Wang designed 6 candidate peptides from ApoE, specifically from residues 148-173 of precursor ApoE, corresponding to the extended putative receptor-binding domain of ApoE, and Wang teaches that the ApoE derived peptides were configured as either single units (monomers) or tandemly repeated unites (tandem dimers); Wang also designed one peptide from the receptor binding domain of ApoB for a total of 7 IDUA-Rb candidates. Seven IDUA-Rb (receptor-binding peptide) fusion candidates were constructed at the C-terminus of IDUA3Myc. All IDUA fusion candidates could be overexpressed and released into the extracellular space from 3T3 cells. The released forms of all IDUA fusion proteins remained catalytically active while bound to anti-myc antibody (e.g. p. 3000, right column, 1st paragraph). Wang describes gene therapy of Hurler syndrome by reprogramming erythroid cells with a tissue-specific lentiviral vector (LV) expressing IDUA, and leading to phenotypic correction in all systematic organs evaluated (e.g. p. 2999, bridging left and right column). Plasmid overexpressing different IDUA fusion candidates from CMV promoter were constructed by using pcDNA3.1 vector (e.g. p. 3004, left column, 2nd paragraph).
It would have been prima facie obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to use a repeat or a tandem repeat of the ApoEII sequence in the IDS fusion protein taught by Heller because Heller teaches a fusion protein comprising a human protein (e.g. IDS) and a BBB carrier peptide including a receptor binding domain of an apolipoprotein (e.g. ApoE2), and a vector expressing the recombinant IDS, and Wang teaches plasmids overexpressing different IDUA fusion candidates including IDUA-Rb (ApoE receptor-binding peptide) fusion candidates and the extended putative receptor-binding domain of ApoE can be monomer or tandem dimers. Both Heller and Wang teach preparation of fusion proteins comprising lysosomal enzyme (IDS taught by Heller and IDUA taught by Wang) and receptor-binding domain (ApoE, ApoE2, ApoE3 and ApoE4 taught by Heller and ApoE taught by Wang). Since Wang also teaches that the receptor-binding domain of ApoE can be monomer or tandem dimers, i.e., tandem repeat, it would be obvious for one of ordinary skill in the art to use tandem repeat of ApoE sequence in the fusion protein comprising a human protein (e.g. IDS) and a BBB carrier peptide including a ApoE receptor binding domain taught by Heller in order to facilitate and optimize the transport of the human protein across the BBB with reasonable expectation of success.
It would have been prima facie obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to use a lentiviral vector to express the IDS-ApoE receptor-binding domain because Heller teaches Suitable expression vector for expressing the recombinant IDS includes AAV based vector, retrovirus based vector and plasmid vectors, and Wang describes gene therapy of Hurler syndrome by reprogramming erythroid cells with a tissue-specific lentiviral vector (LV) expressing IDUA. Both Hurler syndrome (MPS I, IDUS deficiency) and Hunter syndrome (MPS II, IDS deficiency) are mucopolysaccharidosis diseases. Since Heller teaches using retroviral vector, which encompass lentiviral vector, to express recombinant IDS and Wang teaches using lentiviral vector to express IDUS, it would be obvious for one of ordinary skill in the art to use lentiviral vector taught by Wang as a type of retroviral vector taught by Heller so as to express the recombinant IDS with reasonable expectation of success.
One having ordinary skill in the art before the effective filing date of the claimed invention would have been motivated to do so in order to facilitate the transport of the human protein across the BBB as taught by Heller or to engineer a lysosomal enzyme with a derivative of receptor-binding domain of ApoE to enable delivery across the blood-brain barrier as taught by Wang with reasonable expectation of success.
It is noted that claims 11-12 and 19-20 read on the nucleic acid is for use in the treatment, management, retardation of progression or normalization of development of a disease or condition attributable to induronate-2-sulfatase (IDS) deficiency, such as MPS II. The phrase “for use” is an intended use of the nucleic acid and it carries no weight in the prior art rejection. The nucleic acid of claims 11-12 and 19-20 is the same as the nucleic acid of claim 1. Even for the sake of argument, Heller teaches using the BBB carrier peptide-human IDS fusion protein for treating Hunter syndrome (MPS II), thus, it would be obvious for one of ordinary skill in the art to use the nucleic acid encoding the recombinant IDS for the treatment, management or retardation of Hunter syndrome (MPS II).
Claims 1-2 are rejected under 35 U.S.C. 103 as being unpatentable over Heller et al., 2016 (WO 2016/077356 A2, IDS filed 8/21/2023) in view of Wang et al., 2013 (PNAS, Vol. 110, No. 8, p. 2999-3004, IDS filed 8/21/2023) as applied to claim 1 above, and further in view of Lu et al., 2010 (Bioconjugate Chem. Vol. 21, p. 151-156, IDS filed 8/21/2023).
Claims 1-2 are directed to a nucleic acid comprising an iduronate-2-sulfatase (IDS) gene sequence and a repeat of the apolipoprotein E (ApoEII) gene sequence. Claim 2 further comprises an intervening linker sequence located between the IDS sequence and the ApoEII sequence.
With regard to instant claim 1, the combined teachings Heller and Wang renders obvious the claimed nucleic acid , as iterated above in the 103 rejection the content of which is incorporated herein, in its entirety.
Heller and Wang do not specifically teach an intervening linker sequence located between the IDS sequence and the ApoEII sequence.
Lu teaches human IDS protein was fused to the carboxyl terminus of the heavy chain of a chimeric monoclonal antibody (mAb) to the human insulin receptor (HIR) to enable BBB (blood-brain barrier) transport. The HIRMAb-IDS fusion protein was expressed in COS cells (e.g. Abstract). The human IDS cDNA encoding Ser26-Pro550, minus the 25 amino acid signal peptide, was produced by reverse transcription and PCR (e.g. p. 151, right column, last paragraph). The IDS forward PCR primer was a 23-mer coding for 7 amino acids at the beginning of the mature IDS protein, and the primer introduces a Ser-Ser linker between the carboxyl terminus of the CH3 region of the HIRMAb HC and the amino acid terminus of the IDS protein (e.g. p. 152, bridging left column and right column).
It would have been prima facie obvious for one of ordinary skill in the art to use an intervening linker sequence located between the IDS sequence and the ApoEII sequence because Heller teaches a fusion protein comprising a human protein (e.g. IDS) and a BBB carrier peptide including a receptor binding domain of an apolipoprotein (e.g. ApoE2), and Lu teaches human IDS protein was fused to the carboxyl terminus of the heavy chain of a chimeric monoclonal antibody (mAb) to the human insulin receptor (HIR) to enable BBB (blood-brain barrier) transport, and use primer to introduce a Ser-Ser linker between the carboxyl terminus of the CH3 region of the HIRMAb HC and the amino acid terminus of the IDS protein. Both Heller and Lu teach preparation of human IDS-BBB carrier peptide fusion protein and since Lu also teaches introducing a Ser-Ser linker between the carboxyl terminus of the CH3 region of the HIRMAb HC and the amino acid terminus of the IDS protein, it would be obvious for one of ordinary skill in the art to introduce the linker taught by Lu between the IDS sequence and the ApoEII sequence taught by Heller in order to facilitate and optimize the transport of the human protein across the BBB with reasonable expectation of success.
One having ordinary skill in the art before the effective filing date of the claimed invention would have been motivated to do so in order to facilitate the transport of the human protein across the BBB as taught by Heller or to engineer a lysosomal enzyme with a derivative of receptor-binding domain of ApoE to enable delivery across the blood-brain barrier as taught by Wang with reasonable expectation of success.
Claims 1 and 3 are directed to a nucleic acid comprising an iduronate-2-sulfatase (IDS) gene sequence and a repeat of the apolipoprotein E (ApoEII) gene sequence. Claim 3 specifies the IDS sequence comprises a codon-optimized sequence of the wild-type IDS sequence.
Claims 1 and 3 are rejected under 35 U.S.C. 103 as being unpatentable over Heller et al., 2016 (WO 2016/077356 A2, IDS filed 8/21/2023) in view of Wang et al., 2013 (PNAS, Vol. 110, No. 8, p. 2999-3004, IDS filed 8/21/2023) as applied to claim 1, above, and further in view of Diamond et al., 2014 (US 20140186401 A1, effective filing date 4-28-11, IDS filed 8/21/2023).
The teachings of Heller and Wang are as discussed above. Heller and Wang do not specifically teach the IDS sequence comprises a codon-optimized sequence of the wild-type IDS sequence.
Diamond teaches an expression vector having an expression cassette that encodes an SVN gene and the SVN gene may be a codon-optimized SVN (CO-SVN) to increase the efficiency of SVN expression in a particular delivery vehicle. The expression vector can be a plasmid, a viral vector or any other suitable vector that is able to express a recombinant protein or nucleic acid (e.g. [0057]).
It would have been prima facie obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to use the IDS sequence comprising a codon-optimized sequence of the wild-type IDS sequence because both Heller or Wang, and Diamond teach a vector such as a plasmid or viral vector comprising an ORF and Diamond teaches the gene in the vector may be a codon-optimized to increase the efficiency of gene expression in a particular delivery vehicle. It would be obvious for one of ordinary skill in the art to use the IDS sequence comprising a codon-optimized sequence of the wild-type IDS sequence in the vector taught by Heller or Wang in order to increase the expression of the gene in the vector with reasonable expectation of success.
One having ordinary skill in the art before the effective filing date of the claimed invention would have been motivated to do so in order to facilitate the transport of the human protein across the BBB as taught by Heller or to engineer a lysosomal enzyme with a derivative of receptor-binding domain of ApoE to enable delivery across the blood-brain barrier as taught by Wang with reasonable expectation of success.
Claims 1 and 5 are directed to a nucleic acid comprising an iduronate-2-sulfatase (IDS) gene sequence and a repeat of the apolipoprotein E (ApoEII) gene sequence. Claim 5 specifies the IDS sequence comprises the sequence according to SEQ ID No. 2 or a derivative sequence having at least 90% homology thereof.
Claims 1 and 5 are rejected under 35 U.S.C. 103 as being unpatentable over Heller et al., 2016 (WO 2016/077356 A2, IDS filed 8/21/2023) in view of Wang et al., 2013 (PNAS, Vol. 110, No. 8, p. 2999-3004, IDS filed 8/21/2023) as applied to claim 1, above, and further in view of Sugimura et al., 2011 (GeneSeq Accession No. AZM63958, computer printout, pages 1-3).
The teachings of Heller and Wang are as discussed above. Heller and Wang do not specifically teach the IDS sequence comprises the sequence according to SEQ ID No. 2 or a derivative sequence having at least 90% homology thereof.
Sugimura teaches human iduronic-acid 2-sulfatase DNA (SEQ ID NO. 1) sequence, GeneSeq Accession No. AZM63958, which is 100% identical to the sequence of SEQ ID No. 2, and preparation of a vector comprising the gene encoding lysosomal enzyme, introduction of the vector into cells for production of recombinant human lysosomal enzymes.
It would have been prima facie obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to use the IDS sequence comprising the sequence according to SEQ ID No. 2 or a derivative sequence having at least 90% homology thereof because Heller teaches a vector for expressing the recombinant human IDS protein and Sugimura teaches human iduronic-acid 2-sulfatase DNA (SEQ ID NO. 1) sequence, GeneSeq Accession No. AZM63958, which is 100% identical to the sequence of SEQ ID No. 2. Since Sugimura teaches the presence of human IDS DNA sequence, it would be obvious for one of ordinary skill in the art to use the human IDS DNA sequence taught by Sugimura in the vector taught by Heller in order to express the recombinant human IDS with reasonable expectation of success.
One having ordinary skill in the art before the effective filing date of the claimed invention would have been motivated to do so in order to facilitate the transport of the human protein across the BBB as taught by Heller or to engineer a lysosomal enzyme with a derivative of receptor-binding domain of ApoE to enable delivery across the blood-brain barrier as taught by Wang with reasonable expectation of success.
Claims 1, 10, 21 and 27 are directed to a nucleic acid comprising an iduronate-2-sulfatase (IDS) gene sequence and a repeat of the apolipoprotein E (ApoEII) gene sequence. Claim 10 specifies the nucleic acid is transduced in one or more hematopoietic stem and progenitor cells (HSPCs). Claim 21 reads on HSPCs have been removed from the patient, transduced ex vivo with the nucleic acid of claim 1 and the transduced HSPCs administered to the individual. Claim 27 is directed to a combination of a nucleic acid comprising an IDS gene sequence and a repeat of the ApoEII gene sequence and one or more hematopoietic stem and progenitor cells (HSPCs).
Claims 1, 10, 21 and 27 are rejected under 35 U.S.C. 103 as being unpatentable over Heller et al., 2016 (WO 2016/077356 A2, IDS filed 8/21/2023) in view of Wang et al., 2013 (PNAS, Vol. 110, No. 8, p. 2999-3004, IDS filed 8/21/2023) as applied to claims 1, 4, 8-9, 11-12 an 19-20 above, and further in view of Scadden et al., 2008 (US 20080057579 A1, IDS filed 8/21/2023).
The teachings of Heller and Wang are as discussed above. Heller and Wang do not specifically teach transducing the HSPCs with the nucleic acid of claim 1 ex vivo and the transduced HSPCs are administered back to the individual.
Scadden teaches a method for manipulating hematopoietic stem cells and related products (e.g. Abstract). “The hematopoietic stem cells are readily accessible for treatment, particularly in combination with the methods of the invention” (e.g. [0127]). Isolated hematopoietic stem cells can be further manipulated for use in gene therapy applications. The genes can be added to the cells by any known methods. The isolated hematopoietic stem cells using the method of the invention can be transduced with a therapeutic gene (e.g. [0128]). “Methods for expressing exogenous genes in vitro, ex vivo and in vivo are well known in the art… An “ex vivo” in method as used herein is a method which involves isolation of a cell from a subject, manipulation of the cell outside of the body, and reimplantation of the manipulated cell into the subject” (e.g. [0129]).
It would have been prima facie obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to transduce the HSPCs with the nucleic acid of claim 1 ex vivo and the transduced HSPCs are administered back to the individual because Heller teaches suitable expression vector for expressing the recombinant IDS includes AAV based vector and retrovirus based vector, and the vector can be introduced into mammalian cells for the production of recombinant IDS, Wang teaches hematopoietic stem cell (HSC) transplantation or enzyme therapy has been used to treat MPS I (Hurler syndrome) (e.g. p. 2999, left column, last paragraph), and Scadden teaches a therapeutic gene can be transduced into isolated hematopoietic stem cells, and ex vivo method involves isolation of a cell from a subject, manipulation of the cell outside of the body, and reimplantation of the manipulated cell into the subject. Since Wang teaches HSC transplantation has been used to treat MPS I, which is a type of mucopolysaccharidosis, and Scadden teaches transducing isolated HSCs with a therapeutic gene and the ex vivo method for cell therapy, it would be obvious for one of ordinary skill in the art to transduce the HSCs isolated from a subject with the nucleic acid encoding human IDS taught by Heller ex vivo, and reimplant the transduced HSCs back into the subject in order to treat mucopolysaccharidosis including MPS I and MPS II with reasonable expectation of success. It is noted that when the HSCs are contacted with the nucleic acid encoding the recombinant IDS, it reads on the limitation of claim 27, i.e. a combination of the claimed nucleic acid and one or more HSPCs.
One having ordinary skill in the art before the effective filing date of the claimed invention would have been motivated to do so in order to facilitate the transport of the human protein across the BBB as taught by Heller or to engineer a lysosomal enzyme with a derivative of receptor-binding domain of ApoE to enable delivery across the blood-brain barrier as taught by Wang with reasonable expectation of success.
Double Patenting
A rejection based on double patenting of the “same invention” type finds its support in the language of 35 U.S.C. 101 which states that “whoever invents or discovers any new and useful process... may obtain a patent therefor...” (Emphasis added). Thus, the term “same invention,” in this context, means an invention drawn to identical subject matter. See Miller v. Eagle Mfg. Co., 151 U.S. 186 (1894); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Ockert, 245 F.2d 467, 114 USPQ 330 (CCPA 1957).
A statutory type (35 U.S.C. 101) double patenting rejection can be overcome by canceling or amending the claims that are directed to the same invention so they are no longer coextensive in scope. The filing of a terminal disclaimer cannot overcome a double patenting rejection based upon 35 U.S.C. 101.
Claims 1-5, 7-12, 19-21 and 27 is/are rejected under 35 U.S.C. 101 as claiming the same invention as that of claim 1-7 of prior U.S. Patent No. 11,701,390. This is a statutory double patenting rejection. The claims of prior U.S. Patent No. 11,701,390 are provided for ease of reference:
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Claim 1 of US Patent ‘390 is directed to: A nucleic acid comprising an iduronate-2-sulfatase (IDS) gene sequence and a tandem repeat of an Apolipoprotein E (ApoEII) gene sequence, further comprising an intervening linker sequence located between the IDS 5’ sequence and the ApoEII sequence, wherein the intervening linker sequence comprises the sequence according to SEQ ID No. 4 or a derivative sequence having at least 95% homology to SEQ ID No. 4.
Claim 1 of the invention is directed to:
A nucleic acid comprising an iduronate-2-sulfatase (IDS) gene sequence and a
repeat of the Apolipoprotein E (ApoEII) gene sequence.
Claim 2 of the invention is directed to The nucleic acid as claimed in claim 1, further comprising an intervening linker sequence located between the IDS sequence and the ApoEII sequence.
Claim 4 of the invention is directed to the nucleic acid of claim l, wherein the repeat of the ApoEII sequence is in the form of a tandem repeat.
Claim 7 of the invention is directed to the nucleic acid of claim 2, wherein the intervening linker sequence comprises the sequence according to SEQ ID NO: 4 or a derivative sequence having at least 95% homology thereof.
Thus, the claims of the instant application are encompassed by, or overlap in scope significantly with, the claims of US Patent 11,701,390.
Claim 1 is generic to that which is recited in claim 1 of US Patent 11,701,390. Thus, the claims of the instant application are anticipated by claims of US Patent 11,701,390.
Conclusion
Claims 1-5, 7-12, 19-21 and 27 are rejected.
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/KODYE LEE ABBOTT/Examiner, Art Unit 1634
/MARIA G LEAVITT/Supervisory Patent Examiner, Art Unit 1634