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
Claims 15 and 16 are cancelled. Claims 1-14 are pending and under examination.
Claim Objections
Claim 4 is objected to because of the following informalities: the claim contains grammatical errors and convoluted language. The claim may be amended to recite:
The method of claim 1, wherein increasing expression of the AADC polypeptide in the substantia nigra of the subject comprises administering an agent that facilitates localized increase expression of the AADC.
Appropriate correction is required.
Claim Rejections - 35 USC § 112(b)
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 1-3, 11 and 12 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.
Regarding claim 1, increasing expression of AADC is not an active method step. It is a desired result or outcome but the claimed method does not require any operational limitation to carry out the treatment process. Therefore, claim 1, and dependent claims 2 and 3, are indefinite.
Claim 11 recites: wherein another injection of the agent is not performed for at least 1 week prior to or after the single injection. It is unclear if the method requires an additional injection 1 week prior to or after the single injection, or if an additional injection 1 week prior to or after the single injection is optional. In sum, it is unclear how many injections of the agent are required.
Claim 12 recites: wherein another injection of the agent is not performed for at least 30 days prior to or after the single injection. It is unclear if the method requires an additional injection 30 days prior to or after the single injection, or if an additional injection 30 days prior to or after the single injection is optional. In sum, it is unclear how many injections of the agent are required.
Claim Rejections - 35 USC § 112(a)
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.
Claims 1-14 are 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.
MPEP 2163.05 II states “the written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species. A ‘representative number of species’ means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus. See AbbVie Deutschland GmbH & Co., KG v. Janssen Biotech, Inc., 759 F.3d 1285, 1300, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014) (Claims directed to a functionally defined genus of antibodies were not supported by a disclosure that ‘only describe[d] one type of structurally similar antibodies’ that ‘are not representative of the full variety or scope of the genus.’). The disclosure of only one species encompassed within a genus adequately describes a claim directed to that genus only if the disclosure "indicates that the patentee has invented species sufficient to constitute the gen[us].’”
Claims 1-14 encompass a genus of agents that increase expression of an aromatic amino acid decarboxylase (AADC) polypeptide and are drawn to a method of treating Parkinson’s disease comprising increasing expression of AADC in the substantia nigra of a subject suffering from Parkinson’s disease, wherein increasing expression comprises administering a nucleic acid encoding the polypeptide, wherein the nucleic acid shares 70% sequence identity with instant SEQ ID NO:2. The specification has not demonstrated that Applicants are in possession of the entire genus of agents capable of increasing expression of AADC.
The instant specification reduces to practice one AADC variant (Figure 5), but does not disclose the entire genus of AADC variants that are able to catalyze the conversion of L-DOPA to dopamine for the treatment of Parkinson’s disease. The instant specification does not disclose what structural properties are required for the enzyme to convert L-DOPA to dopamine, or disclose which regions of the amino acid sequence of the decarboxylase, are the active site residue(s) for conserving the claimed enzyme activity. The specification does not disclose all nucleic acid sequences up to 30% sequence divergence from instant SEQ ID NO:2 that encode a functional AADC enzyme. Therefore, the disclosed species are not representative of the entire genus of claimed AADC enzyme variants or nucleic acids encoding said AADC enzymes.
Kotin et al., (JP2019010110A) teaches a method for increasing the level of aromatic L-amino acid decarboxylase (AADC) protein in a subject in need thereof wherein the subject has Parkinson’s (p. 51, last two claims) and teaches a polynucleotide encoding AADC for the treatment of Parkinson’s disease (Abstract). However, Kotin does not disclose all possible AADC polypeptide variants that are capable of converting L-DOPA to dopamine, and does not disclose nucleic acid sequences with up to 30% divergence from SEQ ID NO:2 that encode a function AADC enzyme.
In summary, neither the instant specification, nor the prior art, discloses a structure-function relationship between conserved amino acid residues in the claimed enzyme structure and the claimed decarboxylation activity. The instant specification, nor the prior art, discloses a structure-function relationship between conserved nucleic acid residues in the gene sequence and the ability to encode a functional AADC enzyme. One of ordinary skill in the art cannot reasonably predict which residues of an AADC polypeptide may be modified to generate a functional decarboxylase capable of converting L-DOPA to dopamine. One of ordinary skill in the art cannot reasonably predict which nucleic acids of SEQ ID NO:1 may be modified to encode a functional AADC enzyme. Based on the instant disclosure, those skilled in the art would not conclude that the applicant was in possession of all claimed variants.
To obviate the rejection, Applicant may consider the following claim amendment which has been drafted by the Examiner:
Claim 1. A method of treating Parkinson’s disease (PD) comprising administering a nucleic acid encoding the aromatic amino acid decarboxylase (AADC) polypeptide shown in SEQ ID NO:1, or a vector containing the nucleic acid, in the substantia nigra of a subject suffering from PD.
Cancel claim 3.
Cancel claim 4.
Claim 5. The method of claim 4, wherein the nucleic acid consists of SEQ ID NO:2.
Cancel claim 6.
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.
Claims 1, 2, 4, 5, and 7-14 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Kotin et al., (JP2019010110A), cited in the IDS filed 12/15/2025.
Regarding claim 1, Kotin teaches a method for increasing the level of aromatic L-amino acid decarboxylase (AADC) protein in a subject in need thereof wherein the subject has Parkinson’s (p. 51, last two claims), and teaches a polynucleotide encoding AADC for the treatment of Parkinson’s disease (Abstract). Kotin teaches that the AADC polynucleotides may be in a nucleic acid expression vector for administration to a cell (p. 3, para. 5). Kotin teaches that the AADC polynucleotide may be driven by a promoter that provides payload expression for a period of time in a target tissue or sustained expression of payload in neural tissue (p. 5, para. 3-6). Kotin teaches administration of a recombinant AAV vector comprising the AADC polynucleotide to a patient having Parkinson’s disease, and teaches that the substantia nigra was injected (p. 44, Example 5).
Regarding claim 2, Kotin teaches that AADC catalyzes the decarboxylation of L-DOPA to dopamine (p. 3, para. 1).
Regarding claim 4, Kotin teaches that at least one element can be used with the AADC polynucleotides to enhance transgene target specificity and expression i.e., an agent facilitating localized increased expression of the AADC polypeptide (p. 6, para. 2). Kotin teaches injection of the AADC polynucleotide into the substantia nigra (p. 44, Example 5).
Regarding claims 5 and 7, Kotin teaches administration of a recombinant vector comprising the AADC polynucleotide, to a patient having Parkinson’s disease, and teaches that the substantia nigra was injected (p. 44, Example 5).
Regarding claim 8, Kotin teaches that viral vectors comprising the AADC polynucleotide may be used to introduce the polynucleotide into a host cell, and teaches that suitable vectors may be retroviral vectors, adenoviral vectors, adeno-associated vectors, and lentiviral vectors (p. 8, para. 6).
Regarding claim 9, Kotin teaches that the substantia nigra was injected with the AAV encoding the AADC polypeptide (p. 44, Example 5).
Regarding claim 10, Kotin teaches that the viral vector may be administered in a single dose (p. 16, para. 1). Kotin teaches a single injection into the substantia nigra (Example 5, p. 45, para. 4).
Regarding claims 11 and 12, using BRI, it is interpreted that only a single injection of a vector comprising an AADC polynucleotide into the substantia nigra is required, and that an additional injection 1 week or 1 month prior to or after the single injection is optional. As stated, Kotin teaches a single injection into the substantia nigra (Example 5, p. 45, para. 4).
Regarding claim 13, Kotin teaches that the AADC may be administered to a subject who is also receiving levodopa therapy (p. 14, para. 5).
Regarding claim 14, Kotin teaches the administration of carbidopa to the patient (Example 5, p. 46, para. 1)
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 3 is rejected under 35 U.S.C. 103 as being unpatentable over Kotin et al., (JP2019010110A) as applied to claim 1 above, and further in view of UniProt ID A0A0S2Z3N4, integrated into UniProt 2/17/2016.
Kotin teaches a AADC polypeptide sequence (p. 3, para. 7), but does not teach a sequence with 100% sequence identity to SEQ ID NO:1.
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However, UniProt ID A0A0S2Z3N4 teaches a sequence with 100% sequence identity to instant SEQ ID NO:1 (see alignment below).
It would have been obvious to one of ordinary skill in the art, prior to the effective filing date of the claimed invention, to substitute the AADC polypeptide sequence of UniProt ID A0A0S2Z3N4 for the AADC polypeptide sequence of Kotin. One of ordinary skill in the art would have had a reasonable expectation of success because substituting enzymes for those of similar function is well within the knowledge of one of ordinary skill, and the results are reasonably predictable.
Claim 6 is rejected under 35 U.S.C. 103 as being unpatentable over Kotin et al., (JP2019010110A) as applied to claim 5 above, and further in view of Asako et al., (JP2009065969A).
Kotin teaches AADC polynucleotide sequences, i.e., nucleic acid sequences (p. 4, para. 4) but does not teach a nucleic acid sequence with 70% sequence identity to instant SEQ ID NO:2.
However, Asako teaches a gene encoding an AADC enzyme with 100% sequence identity to instant SEQ ID NO:2 (see alignment attached to this Office action).
It would have been obvious to one of ordinary skill in the art, prior to the effective filing date of the claimed invention, to substitute the nucleic acid sequence of Asako for the nucleic acid sequence of Kotin. One of ordinary skill in the art would have had a reasonable expectation of success because substituting genes for those of similar function is well within the knowledge of one of ordinary skill, and the results are reasonably predictable.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to RACHEL EMILY MARTIN whose telephone number is (703)756-1416. The examiner can normally be reached M-Th 8:30-16:00, F 8:30-10:00 EST.
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/LOUISE W HUMPHREY/Supervisory Patent Examiner, Art Unit 1657
/RACHEL EMILY MARTIN/Examiner, Art Unit 1657