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 .
Claim Objections
Claims 1-8 are objected to because of the following informalities:
Claim 1 recites “comprising nucleotide sequence encoding β-globin gene”. It appears that the claim should read “comprising a nucleotide sequence encoding a β-globin gene”.
Claim 2 recites “wherein P-globin gene comprises threonine to glutamine substitution at amino acid position 88 (T88Q)”. It appears that the claim should read “wherein the β -globin gene comprises a threonine to glutamine substitution at amino acid position 88 (T88Q)”.
Claim 3 recites “A viral genome of recombinant lentivirus (LV) particle encoded by nucleotide sequence of SEQ ID NO: 01”. It appears that the claim should read “A viral genome of a recombinant lentivirus (LV) particle encoded by the nucleotide sequence of SEQ ID NO: 01”.
Claim 4 recites “The viral genome of recombinant lentivirus (LV) particle”. It appears that the claim should read “The viral genome of a recombinant lentivirus (LV) particle”.
Claim 4 recites “wherein the expression control elements comprises”. It appears that the claim should read “wherein the expression control elements comprise a”.
Claim 5 recites “wherein the viral vector comprising”. It appears that the claim should read “wherein the vector comprises”.
Claim 6 recites “by nucleotide sequence of SEQ ID NO: 1”. It appears that the claim should read “by the nucleotide sequence of SEQ ID NO: 1”.
Claim 7 recites “administration of nucleotide sequence encoding beta globin gene”. It appears that the claim should read “administration of the nucleotide sequence encoding the beta globin gene”.
Claim 8 recites “administration of nucleotide sequence encoding beta globin gene”. It appears that the claim should read “administration of the nucleotide sequence encoding the beta globin gene”.
Appropriate correction is required.
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 3-8 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.
Claims 3 and 5 recite abbreviations HIV1 PSI, CTS, (HS2-HS3-HS3.2-HS4), and Delta-U3, collectively. It is not readily apparent what structure is required by each of these elements and therefore the claims are not definite.
Claim 5 recites the limitation "wherein said viral vector". There is insufficient antecedent basis for this limitation in the claim because the claim does not previously recite “viral vector”, but rather recites “lentivirus (LV) vector”. Amendment to read “wherein said vector” is suggested.
Claims 4 and 6-8 are rejected because they depend from claims 3 or 5.
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claim 1 is rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
The claim is directed to a lentivirus vector comprising “nucleotide sequence encoding β-globin gene”.
The specification discloses a single nucleotide sequence that encodes a β-globin gene, instant SEQ ID NO: 1 (page 2). The specification does not disclose any other species of nucleotide sequences that encode β-globin genes. The single species is not representative of the entire claimed genus. Without further description of the structure required for the function, one would not be able to recognize that applicant was in possession of the entire genus at the time of filing; and would not be able to readily envision which sequences are necessarily included or excluded from the recited genus.
Efstratiadis et al. (Cell, Vol. 21, 653-666. October 1980) teach that β-like globin genes and their flanking sequences may ultimately provide information relevant to the understanding of the evolution of regulatory pathways. Efstratiadis et al. teach complete nucleotide sequences of genes encoding β-globin genes (page 653) and teach alignment of various β-globin sequences (Figure 5). Efstratiadis et al. is evidence as to the variability of the recited genus.
Additionally, claim 3 recites “expression control elements”, which is a genus that the specification does not adequately describe the structure required for the function. The specification discloses the minimal species of instant claim 4, which are not representative of the entire claimed genus. Without further description of the structure required for the function, one would not be able to readily envision which elements are necessarily included or excluded from the genus of “expression control elements”.
The MPEP states that for a generic claim, the genus can be adequately described if the disclosure presents a sufficient number of representative species that encompass the genus. See MPEP § 2163. If the genus has a substantial variance, the disclosure must describe a sufficient variety of species to reflect the variation within that genus. See MPEP § 2163. Although the MPEP does not define what constitute a sufficient number of representative species, the courts have indicated what do not constitute a representative number of species to adequately describe a broad genus. In Gostelli, the courts determined that the disclosure of two chemical compounds within a subgenus did not describe that subgenus. In re Gostelli, 872, F.2d at 1012, 10 USPQ2d at 1618. Additionally, in Carnegie Mellon University v. Hoffman-La Roche Inc., Nos. 07-1266, -1267 (Fed. Cir. Sept. 8, 2008), the Federal Circuit affirmed that a claim to a genus described in functional terms was not supported by the specification’s disclosure of species that were not representative of the entire genus. Furthermore, for a broad generic claim, the specification must provide adequate written description to identify the genus of the claim. In Regents of the University of California v. Eli Lilly & Co. the court stated:
"A written description of an invention involving a chemical genus, like a description of a chemical species, 'requires a precise definition, such as by structure, formula, [or] chemical name,' of the claimed subject matter sufficient to distinguish it from other materials." Fiers, 984 F.2d at 1171, 25 USPQ2d 1601; In re Smythe, 480 F.2d 1376, 1383, 178 USPQ 279, 284985 (CCPA 1973) ("In other cases, particularly but not necessarily, chemical cases, where there is unpredictability in performance of certain species or subcombinations other than those specifically enumerated, one skilled in the art may be found not to have been placed in possession of a genus ...") Regents of the University of California v. Eli Lilly & Co., 43 USPQ2d 1398.
The claims are rejected under the written description requirement for failing to disclose adequate species to represent the claimed genus, the genus being nucleotide sequences that encode a β-globin gene; and any possible expression control element.
The Guidelines for Examination of Patent Applications under the 35 USC § 112, first paragraph, “Written Description” Requirement”, published at Federal Register, Vol. 66, No. 4, pp. 1099-1111 outline the method of analysis of claims to determine whether adequate written description is present. The first step is to determine what the claim as a whole covers, i.e., discussion of the full scope of the claim. Second, the application should be fully reviewed to understand how applicant provides support for the claimed invention including each element and/or step, i.e., compare the scope of the claim with the scope of the description. Third, determine whether the applicant was in possession of the claimed invention as a whole at the time of filing.
Thus, having analyzed the claims with regard to the Written Description guidelines, it is clear that the specification does not disclose a representative number of species for nucleotide sequences that encode a β-globin gene; or for expression control elements. Thus, one skilled in the art would be led to conclude that Applicant was not in possession of the claimed invention at the time the application was filed.
Claim Rejections - 35 USC § 102
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 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 and 2 is/are rejected under 35 U.S.C. 102(a)(1) and (a)(2) as being anticipated by Sadelain et al. (WO 2019/113321 A1).
Sadelain et al. teaches an expression cassette that allows for the expression of a beta-globin gene or a functional portion thereof, and a lentiviral vector comprising the same (see abstract, claims 1, 39, 40 & 55-57) (instant claim 1).
Sadelain et al. teaches that the expression cassette comprises a human beta-globin gene or a functional portion thereof encoding at least one anti-sickling amino acid residue such as a threonine to glutamine mutation at codon 87 (T87Q), operably linked to a β-globin locus control region (LCR) that comprises a DNase I hypersensitive site-2 (HS2) region, a DNase I hypersensitive site-3 (HS3) region, and a DNase I hypersensitive site-4 (HS4) region, a human β-globin promoter, and a human β-globin 3' enhancer positioned upstream of the globin gene or functional portion thereof (claims 42, 43, and 45). The threonine to glutamine mutation at codon 87 (T87Q) corresponds to amino acid position 88 (instant claim 2).
The primary sequence of haemoglobin subunit beta has 147 amino acids with initiator methionine at position 1 and threonine at position 88, whereas the actual peptide is 146 amino acids long with the first amino acid being valine as initiator methionine is removed during post-translational processing which is why the amino acids are numbered from valine (the second amino acid in the primary sequence) in which case, threonine is present at position 87. In fact, there is no T88 (threonine at position 88) in the haemoglobin subunit beta but only leucine. Hence, the mutation T88Q in beta-globin gene stated in present claims is the same as the T870 in the beta-globin gene of expression cassette of Sadelain et al.
Sadelain et al. teaches a recombinant vector comprising the said expression cassette wherein the said vector is a retroviral vector such as lentivirus vector, which further comprises a heterologous promoter, one or more left and right long terminal repeat sequences (LTR) in native or truncated form, a packaging signal, RRE (Rev response element of HIV-1), cPPT and a polyadenylation signal (see claims 1, 39-43, 45, 46, 49, 53-57, 59 & 60, lines 10-15 on page-101, example-5 and figure-1).
Therefore, the claims are anticipated by Sadelain et al.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 1-8 is/are rejected under 35 U.S.C. 103 as being unpatentable over Sadelain et al. (WO 2019/113321 A1), in view of Miccio et al. (WO 2018/220210 A1), and Negre et al. (WO 2013/043196 A1).
Sadelain et al. teaches an expression cassette that allows for the expression of a beta-globin gene or a functional portion thereof, and a lentiviral vector comprising the same (see abstract, claims 1, 39, 40 & 55-57) (instant claim 1).
Sadelain et al. teaches that the expression cassette comprises a human beta-globin gene or a functional portion thereof encoding at least one anti-sickling amino acid residue such as a threonine to glutamine mutation at codon 87 (T87Q), operably linked to a β-globin locus control region (LCR) that comprises a DNase I hypersensitive site-2 (HS2) region, a DNase I hypersensitive site-3 (HS3) region, and a DNase I hypersensitive site-4 (HS4) region, a human β-globin promoter, and a human β-globin 3' enhancer positioned upstream of the globin gene or functional portion thereof (claims 42, 43, and 45). The threonine to glutamine mutation at codon 87 (T87Q) corresponds to amino acid position 88 (instant claim 2).
The primary sequence of haemoglobin subunit beta has 147 amino acids with initiator methionine at position 1 and threonine at position 88, whereas the actual peptide is 146 amino acids long with the first amino acid being valine as initiator methionine is removed during post-translational processing which is why the amino acids are numbered from valine (the second amino acid in the primary sequence) in which case, threonine is present at position 87. In fact, there is no T88 (threonine at position 88) in the haemoglobin subunit beta but only leucine. Hence, the mutation T88Q in beta-globin gene stated in present claims is the same as the T870 in the beta-globin gene of expression cassette of Sadelain et al.
Sadelain et al. teaches a recombinant vector comprising the said expression cassette wherein the said vector is a retroviral vector such as lentivirus vector, which further comprises a heterologous promoter, one or more left and right long terminal repeat sequences (LTR) in native or truncated form, a packaging signal, RRE (Rev response element of HIV-1), cPPT and a polyadenylation signal (see claims 1, 39-43, 45, 46, 49, 53-57, 59 & 60, lines 10-15 on page-101, example-5 and figure-1).
Sadelain et al. does not teach incorporation of every element recited in claims 3 and 5. Claims 3 and 5 recite abbreviations HIV1 PSI, CTS, (HS2-HS3-HS3.2-HS4), and Delta-U3, collectively. It is not readily apparent what structure is required by each of these elements. The cited references are evidence that design of expression cassette elements in lentiviral vectors for expression of a beta-globin gene was routine in the art. The instant claims do not require any specific configuration of any specific structures that applicant has demonstrated an unexpected result with. Choice of suitable expression control elements which also didn't have an associated unforeseen technical effect, would be well within the conventional expertise of a person skilled in the art.
Miccio et al. discloses a recombinant lentiviral vector comprising in its genome a nucleotide sequence encoding a protein such as beta-globin and variants such as a beta-globin gene comprising a T87Q mutation (see claim 1, page-8 and fig-14), a self-inactivating LTR configuration, a packaging signal such as HIV-1 psi, a Rev Response Element (RRE) to enhance nuclear export of unspliced recombinant lentiviral vector RNA, a central polypurine tract (cPPT) to enhance nuclear import of recombinant lentiviral vector genomes, and LCR (see lines 11-20 on page-11 and example-1). The threonine to glutamine mutation at codon 87 (T87Q) corresponds to amino acid position 88 (instant claim 2).
Negre et al. teach gene therapy vectors for the treatment of conditions associated with hematopoietic system such as thalassemia, and discloses a lentiviral vector comprising a left (5') and a right (3') retroviral LTR, a hematopoietic cell expression control sequence operably linked to a gene of interest wherein the hematopoietic cell expression control sequence comprises a human beta-globin promoter; a human beta-globin locus control region (LCR), wherein the gene of interest is human beta-globin encoding a threonine to glutamine mutation at codon 87 (T87Q).
Negre et al. teach that the vector can have a heterologous promoter such as a Rous Sarcoma Virus (RSV) promoter, one or more Psi packaging sequences, RRE, a central polypurine tract/DNA flap (cPPT/FLAP), a retroviral export element, a polyadenylation of sequence such as AAТААА, АТТААА or AGTAAA (see abstract, claims 1, 4, 6, 7, 24-28, 30, 39, 44-47, 55 & 62 and figure-1). For the same reasons already mentioned (supra), the mutation T88Q of the beta-globin gene stated in present claims is the same as the T87Q in the beta-globin gene of the lentiviral vector of Negre et al.
This is further evident from the peptide of Seg ID No: 7 of Negre et al. which sets forth an amino acid sequence of the 147 AA long mutant human beta-globin polypeptide wherein glutamine (Q) is seen at position 88 but since the initiator methionine which is later removed is usually not numbered, said residue will be identified as Q87 in usage, resulting from the T870 mutation in the gene encoding the mutant peptide.
It is noted that claims 7 and 8 recite outcomes rather than method steps and would therefore necessarily flow from the method steps.
Conclusion
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/AMY ROSE HUDSON/Primary Examiner, Art Unit 1636