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 Status
Claims 1-13, 15-16, 18-22 are pending on the application.
Claims 1-7, 12-13, 15-16 and 18-20 are examined on the merits.
Priority
The applicant’s application is a U.S. National Stage application of PCT International Patent Application Serial No. PCT/GB2021/051985, filed July 30, 2021, which itself claims the benefit of Great Britain Patent Application Serial No. GB2011871.7, filed July 30, 2020 is acknowledged.
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Election/Restrictions
Applicant’s election without traverse of Group I corresponding to claims 1-7, 12-13, 15-16 and 18-20 in the reply filed on 10/15/2025 is acknowledged.
Applicant elects for examination (I) SEQ ID NO:1 as the amino acid insert selected from the amino acid insert sequences recited in claim 1, (II) SEQ ID NO:11 as the AAV capsid protein selected from the AAV capsid protein sequences recited in claim 7, and (III) (d) the macrophage-specific promoter or enhancer derived from CD11b as the macrophage- specific promoter or enhancer listed in claim 16, without traverse.
Claims 8-11, 21-22 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected Group, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 11/24/2025.
Claim Rejections - 35 USC § 112
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 5-6 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.
Claim 5 is drawn to the AAV capsid protein. The rejected claim, comprise the unmodified AAV capsid protein which is a wild-type PHP.eB capsid protein, or an AAV capsid protein comprising a sequence having at least 80% sequence identity to SEQ ID NO: 10. The dependent claim 6 is drawn to the AAV capsid protein of claim 5, wherein the amino acid sequence is inserted between amino acids 588 and 589 of SEQ ID NO: 10, or at an equivalent position in a sequence having at least 80% sequence identity to SEQ ID NO: 10.
To provide adequate written description and evidence of possession of a claimed genus, the specification must provide sufficient distinguishing identifying characteristics of the genus. The factors to be considered include disclosure of a complete or partial structure, physical and/or chemical properties, functional characteristics, structure/function correlation, and any combination thereof.
The specification describes creation of novel AAV capsid proteins that can be introduced into AAV viral particles. AAVs having the modified capsid proteins are capable of crossing the blood brain barrier to efficiently target cells throughout the CNS, including microglia and brain macrophages, which include CNS-infiltrating macrophages derived from recruited monocytes. (e.g., lane 28, page 2). The specification envisions the modified AAV capsid protein having an insertion sequence in the binding arm is a wild-type PHP.eB capsid protein having the sequence of SEQ ID NO: 10. The modified AA V capsid protein of the present invention
also encompasses variants of SEQ ID NO: 10 that differ in sequence from SEQ ID NO: 10, but retain the ability to form viral particles that can infect and/or transduce microglia or brain macrophages. Such sequences have at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 98% or at least 99% sequence identity to SEQ ID NO: 10 (e.g., lane 12, page 13). The specification envisions the amino acid sequence of SEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8 or 9, or a variant thereof as described above is inserted between amino acids 588 and 589 of SEQ ID NO: 10. For example, the amino acid sequence of SEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8 or 9 or any one of SEQ ID NOs: 147-150, 162-164 and 176-181 is inserted
30 between amino acids 588 and 589 of SEQ ID NO: 10. In the context of infecting and/or transducing microglia or brain macrophages, the amino acid sequence of any of the insertion sequences set out in Table 4 (SEQ ID NOs: 54 to 207) can be inserted between amino acids 588 and 589 of SEQ ID NO: 10 (e.g., lane 26, page 14).
No description is provided of any modifications of SEQ ID NO: 10, with at least 80%, homology that retain the ability to maintain transduction efficiency.
The examples described in the specification does not meet the limitation of the rejected claims (at least 80%, identity), the examples are only representative of random library screen of the PHP.eB capsid capable of infecting microglia. “At least 80 % identity” encompasses a very large number of different amino acid sequences (i.e., every sequence at least 80% identical to SEQ ID NO: 10), but there is insufficient guidance provided indicating any of the elements that are critical to the functioning of the polypeptide, thus it cannot be determined which amino acids can be changed without disrupting the function of the polypeptide; thus further experimentation would be required to determine which variants of SEQ ID NO: 10 are functional and which are not.
As such, the claims encompasses significantly more than what is disclosed in the specification and does not satisfy the written description requirement under 35 U.S.C 112(a).
Therefore, the skilled artisan would have reasonably concluded applicants were not in possession of the claimed invention for claims 5-6.
The claims listed in the statement of rejection but not otherwise discussed are rejected because they are similarly not limited to particular polynucleotides that are considered to be adequately described by the specification.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JULIO GOMEZ RODRIGUEZ whose telephone number is (571)270-0991. The examiner can normally be reached Monday - Friday 8:00 am - 5:00 pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Jennifer Dunston can be reached at 5712722916. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/JULIO WASHINGTON GOMEZ RODRIGUEZ/Examiner, Art Unit 1637
/J. E. ANGELL/Primary Examiner, Art Unit 1637