Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
DETAILED ACTION
1. Applicant’s amendment and response filed 6/24/25 is acknowledged and has been entered.
2. Applicant is reminded of Applicant's election without traverse of Group I and species of nucleic acid molecule encoding a signal sequence, a luminal domain of a lysosomal LAMP-1 protein, an allergen domain of CryJ2, the TM domain of LAMP-1, and a targeting domain of LAMP-1 in Applicant’s amendment and response filed 5/28/24.
Claims 15-19, 22, 24, 25, 27 and 29-34 are presently being examined as the read upon Applicant’s elected species SEQ ID NO: 3.
3. Applicant’s amendment filed 6/24/25 has overcome the prior rejection of record of claims 31-33 under 35 U.S.C. 101 and section 33(a) of the America Invents Act as being directed to or encompassing a human organism.
Applicant has amended the claims to recited that the cell is isolated.
4. Applicant’s amendment filed 6/24/25 has overcome the prior rejection of record of claims 15-19, 22, 24, 25, 27 and 29-34 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the enablement requirement.
Applicant has amended the claims to recite that the amino acid sequence identity is at least 95% or 98% identical to the recited sequence.
5. 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.
6. The following is a quotation of pre-AIA 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negated by the manner in which the invention was made.
7. Claims 15-19, 22, 25, 27 and 29-34 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over US 8,318,173 (IDS reference) in view of Hashimoto et al (Clin. Exp. Allergy, 1995, 25: 848-852, of record) and Holgate and Polosa (Nature, 2008, 8: 218-230, IDS reference).
This is a new ground of rejection necessitated by Applicant’s amendment filed 6/24/25.
Claim interpretation: The instant specification discloses at [013] that the signal sequence is provided to direct the encoded protein to the endoplasmic reticulum or a lysosome. The specification discloses that “Typically, the allergen domain comprises one or more allergen proteins, although in embodiments, immunogenic polypeptide or peptide fragments of allergenic proteins can be used” ([013]). Therefore the allergen domain may comprise an entire allergen polypeptide or protein or may comprise or consist of a fragment(s) of an allergen protein. In addition, the instant claims recite the open transitional phrase “comprising” opening the recited nucleic acid molecule or pharmaceutical composition thereof to comprise additional non-recited portions and/or ingredients. As pertains to the sequences recited in the instant claims that comprise the IOSD of LAMP-1 (see for example Figure 1 and the specification at [089]-[093], Applicant has stated on the record that the term “luminal domain of a lysosomal associated membrane (LAMP) protein” in claim 15 is clear that the domain represents the entire luminal region of LAMP-1. Applicant further states that the ISOD is disclosed in the specification to be the luminal domain of LAMP-1 and that Figs 1,3 and 4 show the allergen inserted between the ISOD (the intra-organelle stabilizing domain) and the TM domain (see page 6 of the response filed 11/1/24).
Instant base claim 15 recites a nucleic acid molecule encoding a polypeptide, wherein the polypeptide comprises an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO: 3 (Applicant’s elected species). Instant dependent claims 25 and 27 recite at least 98% identical to SEQ ID NO: 3.
The Examiner notes that instantly recited SEQ ID NO: 3 (i.e, a sequence 100% identical to SEQ ID NO: 3) comprises in N- to-C-terminal order, a signal sequence from LAMP-1, an ISOD from LAMP-1, a two amino acid linker, the Cryj2 allergen protein sequence, a two amino acid linker, the TM region of LAMP-1, and the same targeting sequence disclosed by the primary art reference cited below in this rejection.
US 8,318,173 discloses a nucleic acid molecule, including DNA or other polynucleotide sequence, or a vector comprising DNA, vaccine thereof, or other polynucleotide sequence such as RNA, and host cell comprising the said vector, including wherein the host cell is an antigen presenting cell, and further including pharmaceutically acceptable carriers, and pharmaceutical composition thereof, the nucleic acid molecule encoding a chimeric polypeptide that comprises a signal sequence, the luminal domain of a LAMP polypeptide (including a mammalian LAMP polypeptide such as human LAMP), more than one antigen, including wherein the antigens can be allergens, a transmembrane and cytoplasmic domain of LAMP that comprises a tetrapeptide sequence Y-Xaa-Xaa-Xbb (wherein X is any amino acid residues and Xbb is a hydrophobic residue, and including such a sequence as GYQTI that is the targeting domain of LAMP that targets a protein to an endosomal/lysosomal compartment or lysosome-related organelle for processing and MHC II loading). US 8,318,173 discloses constructs that comprise a signal sequence, a luminal domain followed by an antigen followed by a transmembrane and cytoplasmic domain comprising the trafficking tetrapeptide. 8,318,173 discloses that inter-nucleotide linkers may be interspersed between components. 8,318,173 discloses that these constructs are beneficial and advantageous in delivering antigens to MHC II processing/loading compartments, that this approach increases cellular and humoral responses to the MHC II peptides generated in said compartments and results in presentation of an increased number of epitopes. US 8,318,173 discloses that the domains of the chimeric construct may be provided in sequence or separated by nucleic acids encoding linker polypeptides. (See entire reference, especially column 3 at lines 44-51, column 4 at lines 28-63, paragraph spanning columns 7-8, column 14 at lines 17-67, paragraph spanning columns 6-7, column 15 at lines 1-9 and 36-39, column 18 at lines 52-57, column 19 at lines 44-55, paragraph spanning columns 23-24, column 24 at lines 24-26, column 27 at lines 15-38, column 28 at lines 2-5, Figures, claims).
US 8,318,173 does not disclose that the allergens are those of Cryj2.
Hashimoto et al teach that Cry J II (i.e., Cry J2 or Cryj2) is as important a major allergen as Cry j1, both of which are allergens from Japanese cedar (Cryptmeria japonica: CJ), that cause pollinosis (see entire reference, especially abstract and introduction, col. 26 at lines 59-63).
Holgate and Polosa teach that allergen-specific immunotherapy (SIT) induces immunological tolerance and induction of blocking IgG4 antibodies through repeated exposure to allergens and a decrease in the level of allergen-specific IgE antibodies (see entire reference, especially section spanning pages 221-222).
It would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made to have used the coding sequences for the Cryj2 allergen as the antigens in the nucleic acid construct disclosed by 8,318,173, either contiguously arranged or separated by an inter-nucleotide linker as is also disclosed by 8,318,173.
One of ordinary skill in the art would have been motivated to do this in order to create and use a nucleic acid molecule for treating Japanese cedar pollinosis, and with a reasonable expectation of success in doing so.
The instant claims are also included in this rejection for the following reasons. At least 95% identity to SEQ ID NO: 3 requires that 866 amino acid residues must be identical, while 45 may be different. At least 98% identity to SEQ ID NO: 3 requires 893 amino acid residues to be identical, while 18 may be different. The components of the art sequence are identical to instantly recited SEQ ID NO: 3 but for the presence in SEQ ID NO: 3 of a specific two amino acid residue linker between the IOSD and the CryJ2 sequence (i.e., amino acid residues 381-382) and a specific two amino acid residue linker between the sequence of CryJ2 and the TM (i.e., amino acid residues 1233-1234). Four amino acid residues difference is well within the number of amino acid residues that may be different, i.e, ranging from 45 to 18 for at least 95% and for at least 98% identity, respectively. In addition, the primary art reference discloses that generic peptide linkers may be interposed between components.
Applicant’s arguments have been fully considered but are not persuasive. Applicant’s said arguments are of record in the amendment and response filed 6/24//25 on pages 3-6.
Applicant presents largely the same arguments as those of record, and the Examiner’s rebuttal to said prior arguments also apply hereto, as they equally apply to the claims as presently amended by Applicant. As to Applicant’s further arguments that the claims reciting [a nucleic acid molecule encoding a polypeptide that comprises] an amino acid sequence at least 98% identical to SEQ ID NO: 3 (i.e., the combination of the cited references does not provide a motivation or a reasonable expectation of success in obtaining the recited nucleic acid molecule), these arguments have been addressed in the said prosecution history. In brief, the primary art reference teaches the presently recited components of the chimeric protein save the specific CryJ2 allergen protein and the two aforementioned 2-amino acid residue linkers between the luminal domain of LAMP-1 and the generic allergen portion and the TM of LAMP-1 of the primary reference art construct, and nucleic acid molecule encoding it. The Hashimoto reference teaches that Cry J2 is an important major allergen of Japanese cedar allergen, while Holgate and Polosa teach allergen-specific immunotherapy through repeated exposure to allergens, providing motivation to combine the references, as is enunciated in the instant rejection. The argument of reasonable expectation of success is addressed in the prosecution history of record.
8. No claim is allowed.
9. Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
10. Any inquiry concerning this communication or earlier communications from the examiner should be directed to MARIANNE DIBRINO whose telephone number is (571)272-0842. The examiner can normally be reached on M, T, Th, F.
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/Marianne DiBrino/
Marianne DiBrino, Ph.D.
Patent Examiner
Group 1640
Technology Center 1600
/MICHAEL SZPERKA/Primary Examiner, Art Unit 1641
Prosecution Insights