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 .
Status of Claims
Claims 1, 4-5, 8-9, 13, 15, 132-139, and 143 are pending and examined herein.
Claims 2-3, 6-7, 10-12, 14, 16-131 and 140-142 are cancelled.
Withdrawn Rejections
The rejection of claims 135-137 on the grounds of 35 U.S.C. 112(a) as failing to comply with the written description requirement has been modified, necessitated by amendments filed 11/26/2025.
The rejection of claims 1-2, 4-5, 8-9, 13, 132-134, 139, and 141-142 on the grounds of 35 U.S.C. 101 has been withdrawn, necessitated by amendments filed 11/26/2025. The addition of selecting AAV capsid proteins if it specifically binds to CD59A to independent claim 1 adds significantly more to the judicial exception.
The rejection of claims 1-2, 4-5, 8-9, 13, 132-134, 139, and 141-142 on the grounds of 35 U.S.C. 102(a)(1) has been withdrawn, necessitated by amendments filed 11/26/2025.
Claim Interpretation
In light of the section heading “In vitro binding assays” on page 55 of the applicant’s specification, “selecting the AAV capsid protein if it specifically binds to the protein of the Ly6/uPAR [lymphocyte antigen-6/urokinase-type plasminogen activator receptor] protein family attached to the surface of the cell” is interpreted as equivalent to “selecting the AAV capsid protein if it transduces a cell with a protein of the Ly6/uPAR [lymphocyte antigen-6/urokinase-type plasminogen activator receptor] protein family attached to the surface of that cell”. On page 55, the specification recites, “The viruses that remained bound to the cells were extracted with TRIzol (Invitrogen)”. According to the product page Invitrogen TRIzol reagent (TRIzol™ Reagent 100 mL | Buy Online | Invitrogen™ | thermofisher.com), the reagent “[o]ffers superior lysis capability”. Because the binding assays of the specification involve an extraction step with lysis of the cells, the results will indicate both viruses bound to the cells and viral transduction, therefore, the two are indistinguishable and will be treated as equivalent for purposes of claim interpretation.
It is noted that the specification discloses multiple methods for the AAV capsid selecting steps. In addition to the in vitro binding assays, the specification discloses the use of purified fusion proteins in virus pull down assays (see, e.g., p. 62, under “Virus pull down with purified Fc-tagged protein”; and p. 77, under “Example 10: Purified Fc-fusion proteins can be used to identify novel AAV capsids that bind to specific receptors.”). However, the fusion proteins are not on the surface of cells as described in the claims. Under the section “Western blotting and virus overlay assays” on page 53, the specification discloses assays to measure the interaction between capsid proteins and target proteins from protein lysates. However, the target proteins from the cell lysates are no longer on the cell surface when the interaction is measured. Under the section “Luciferase transduction assay” on page 55-56, the specification discloses a transduction assay utilizing the enzyme luciferase. The assay is clearly measuring transduction, not binding. None of the methods disclose a selecting step by simply measuring binding of the AAV capsid proteins to proteins the Ly6/uPAR protein family. Furthermore, even if arguendo, the selecting step involves simply measuring the binding between the AAV capsid protein and the protein of the Ly6/uPAR protein family, it is unclear how the binding is detected.
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 135-137 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 claims contain 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 inventors, at the time the application was filed, had possession of the claimed invention. This is a new matter rejection.
The examiner is unable to find support for the newly added claims 135-137, i.e., “A method comprising: […] wherein the protein of the Ly6/uPAR protein family is a fusion protein, and wherein the protein of the Ly6uPAR protein family is CD59A”. Applicant states that support for the amendment can be found throughout the specification and claims as originally filed. However, the specification teaches the use of purified fusion proteins in virus pull down assays (see, e.g., p. 62, under “Virus pull down with purified Fc-tagged protein”; and p. 77, under “Example 10: Purified Fc-fusion proteins can be used to identify novel AAV capsids that bind to specific receptors.”). It does not provide support for cells expressing CD59a fusion proteins on the surface thereof. Applicant is required to cancel the new matter in response to this office action.
Should applicant disagree with the examiner’s factual determination above, applicant should provide evidence that either or both of the provisional applications provide support for the invention now claimed in the manner required by 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph. This could be accomplished, for example, by pointing to the specific page and line numbers within the specification, which disclose each limitation of the claimed invention.
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.
Claim 8 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 8 recites the method of claim 1 wherein that the protein of the Ly6/uPAR protein family is a human protein. However, claim 1 recites wherein the protein of the Ly6/uPAR protein family is CD59A. CD59A is a mouse protein (see, e.g., applicant’s specification, p. 36, para. 4). It is unclear how the protein is both a human protein and a mouse protein. Therefore, the metes and bounds of the claim cannot be ascertained.
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 134 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. Claim 134 recites, “The method of claim 1, wherein the method is a method for identifying an AAV capsid protein that can cross the blood-brain barrier”. The wherein clause merely recites intended use of the method. The clause does not further limit the steps of the method itself, therefore, the claim is improperly dependent. Applicant may cancel the claim, amend the claim to place the claim in proper dependent form, rewrite the claim in independent form, or present a sufficient showing that the dependent claim complies with the statutory requirements.
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 135-137 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Sivasankar, et al. (“CD59a deficient mice display reduced B cell activity and antibody production in response to T-dependent antigens”, published 2007-02-12).
With regards to claims 135-137, Sivasankar teaches a method comprising providing a targeting peptide, incubating the targeting peptide with a CD59A Fc fusion protein, and selecting the targeting protein if it specifically binds to the CD59A fusion protein (see, e.g., p. 2979, col. 2, under “2.3 Flow cytometry”, para. 1: “For binding of CD59a-IgG2a fusion protein, splenocytes were incubated with cell specific markers and biotinylated CD59a-IgG2a fusion protein, or an irrelevant mAb of the IgG2a istotype [sic] as a control, at various dilutions for 30 min on ice. After three washes, cells were stained with SA-PE, washed and fixed in 1% paraformaldehyde prior to flow cytometry using a BD FACScalibur”). It is understood the cell specific markers are targeting peptides and the selection is completed by staining. It is understood that the CD59A-IgG2a fusion protein is a Fc fusion protein because IgG2a comprises a Fc portion. It is understood that the fusion of CD59A with IgG2a comprises an Fc-tag.
Conclusion
Claims 1, 4-5, 8-9, 13, 15, 132-134, 138-139, and 143 are free of the prior art. However, claims 8 and 134 are rejected as stated above.
The following is a statement of reasons for allowance of claims 1, 4-5, 9, 13, 15, 132-133, 138-139, and 143 :
The prior art of record does not teach or make obvious independent claim 1:
“A method comprising:
providing an adeno-associated virus (AAV) capsid protein;
contacting the AAV capsid protein with a cell that expresses a protein of the lymphocyte antigen-6 (Ly6)/urokinase-type plasminogen activator receptor (uPAR) protein family attached to the surface of the cell; and
selecting the AAV capsid protein if it specifically binds to the protein of the Ly6/uPAR protein family attached to the surface of the cell; wherein the protein of the Ly6/uPAR protein family is expressed recombinantly in the cell, and wherein the protein of the Ly6/uPAR protein family is CD59A.”
The closest art of record is Deverman (WO 2017100671 A1, published 2017-06-15, cited in PTO-892 dated 07/30/2025) as evidenced by Huang, et al. (“Delivering genes across the blood-brain barrier: LY6A, a novel cellular receptor for AAV-PHP.B capsids”, published 2019-11-14, cited in PTO-892 dated 07/30/2025). Deverman teaches a method for selecting an AAV capsid protein, specifically AAV-PHP.N (also referred to as AAV-PHP.eB), with greater central nervous system transduction by providing an AAV capsid protein and contacting it with a cell (see, e.g., under “FIG. 4A”; p. 51, para. [0153]-[0154]; p. 21, para. [0050]; and p. 52, para. [0156]). The selection method disclosed in Deverman (titled the CREATE method) includes recovering vector DNA from mouse tissue samples transduced by AAV capsid proteins and selecting the AAV capsid protein variants that showed evidence of enrichment in the tissues (see, e.g., p. 57, under “In vivo selection”, para. [0170]-[0171]). The transduction described is considered to involve binding as discussed above in the claim interpretation section. While when Deverman was published the receptor for AAV-PHP.N was unknown, Huang discloses that an “essential receptor” was Ly6a of the Ly6/uPAR protein family, as in claim 1 (see, e.g., p. 1, under “Abstract”). Huang provided comprehensive evidence that Ly6a is responsible for the AAV capsid transduction in mice models by transfecting green fluorescent protein (GFP) into a strain of mice with high levels of Ly6a and a strain of mice with low levels of Ly6a (see, e.g., AAV capsid protein GFP transduction – p. 3, under “Fig 1.”, panel “A”; Ly6a levels - p. 5, under “Fig 2”, panel “C”). The mice strain with high levels of Ly6a were transduced by the AAV capsid protein at a higher level, indicating that Ly6a is involved with the AAV capsid protein transduction. Huang discloses they “identified a single missense variant in Ly6a, out of a starting pool of millions of genetic variants, which segregates with efficient CNS transduction by AAV-PHP.eB” (see, e.g., p. 9, para. 2). Furthermore, while Huang does not identify Ly6a as the only receptor involved in AAV capsid protein transduction, page 40 of the applicant’s specification recites “’specific binding’ or ‘preferential binding’ does not necessarily require (although it can include) exclusive binding” (see, e.g., p. 40, para. 3). However, Deverman fails to teach the Ly6a/uPAR protein is CD59A.
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MICHAEL C SVEIVEN whose telephone number is (703)756-4653. The examiner can normally be reached Monday to Friday - 8AM to 5PM PST.
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/MICHAEL CAMERON SVEIVEN/Examiner, Art Unit 1678
/GREGORY S EMCH/Supervisory Patent Examiner, Art Unit 1678