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 the Claims
The amendment filed 8/15/2025 has been entered. Claims 1 and 9 have been amended. Claims 1-9, 11, 15-23, and 25 are currently pending and claims 15-23 and 25 are withdrawn. Claims 1-9 and 11 are examined herein.
Status of the Rejection
All 35 U.S.C. § 103 rejections from the Non-Final Office Action filed 5/22/2025 are withdrawn in view of the Applicant’s amendment.
New grounds of rejection under 35 U.S.C. § 112(a) and 112(b) are necessitated by the amendments as outlined below.
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 1-9 and 11 rejected 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. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
Claim 1 recites:
A method of separating viral vectors in a sample, the method comprising:
performing capillary isoelectric focusing (cIEF) on the sample comprising viral vectors containing exogenous polynucleotide under conditions and for a duration sufficient to separate the viral vectors based on the isoelectric point (pI) of each viral vector, wherein the viral vectors are free of a capsid;
generating a readout of cIEF results; and
analyzing the readout to identify the viral vectors based on exogenous polynucleotide content.
Case law holds that applicant’s specification must be “commensurately enabling [regarding the scope of the claims]” Ex Parte Kung, 17 USPQ2d 1545, 1547 (Bd. Pat. App. Inter. 1990). Otherwise, undue experimentation would be involved in determining how to practice and use applicant’s invention. The test for undue experimentation as to whether or not all embodiments within the scope of claim 1 can be used as claimed and whether claim 1 meets the test is stated in Ex parte Forman, 230 USPQ 546, 547 (Bd. Pat. App. Inter. 1986) and In re Wands, 8 USPQ2d 1400, 1404 (Fed.Cir. 1988). Addressing now the “Wands” factors (MPEP 2164.01(a)):
(A) The breadth of the claims: The claims are narrow in scope as they concern a method of separating viral vectors comprising performing capillary isoelectric focusing (cIEF) on a viral vector sample containing exogenous polynucleotide content, wherein the viral vectors are free of a capsid, and analyzing the resulting cIEF readout to identify the viral vectors based on exogenous polynucleotide content.
(B) The nature of the invention: The invention is directed to a method of separating viral vectors based on cIEF, wherein the viral vectors are free of a capsid, wherein the viral vectors are separated into vectors with full-length exogenous polynucleotide, vectors with exogenous polynucleotide fragments, or vectors lacking any exogenous polynucleotide based on their isoelectric points, as vectors with full-length exogenous polynucleotide have a lower pI relative to vectors with exogenous polynucleotide fragments and vectors with no exogenous polynucleotide.
(C) The state of the prior art: CIEF of viruses, viral vectors, and virus-like particles containing capsid protein is well known in the art. Schnabel et al. (“Determination of the pI of Human Rhinovirus Serotype 2 by Capillary Isoelectric Focusing,” 1996, Anal. Chem., vol. 68, pgs. 4300-4303) teaches a method of performing cIEF on a sample containing human rhinovirus serotype 2 [pg. 4300, Abstract], wherein the sample contains capsid proteins [pg. 4300, col. 2, para. 2]. Redfern et al. (“Addressing Key Attributes of Viral Vectors,” 2019, Bioprocess International) teaches that imaged cIEF is applicable to recombinant adeno-associated viral vectors (rAAVs) that include capsid protein [pg. 4, para. 3; pg. 5, col. 2, para. 3]. Goodridge et al. (“Isoelectric Point Determination of Norovirus Virus-like Particles by Capillary Isoelectric Focusing with Whole Column Imaging Detection,” 2004, Analytical Chemistry, vol. 76, pgs. 48-52) teaches a method of separating virus-like particles in a sample (applying capillary isoelectric focusing-whole column imaging detection [cIEF-WCID] to separate norovirus virus-like particles [VLPs] [pg. 48, col. 1, para. 1; pg. 52, col. 2, para. 3]), wherein the virus-like particles comprise only capsid protein [pg. 50, col. 1, para. 6].
(D) The level of one of ordinary skill: The level of one of ordinary skill in the art would be high as performing cIEF on a viral vector sample requires knowledge of electrophoresis and viral vector synthesis/isoelectric behavior.
(E) The level of predictability in the art: applying cIEF to a viral vector without capsid (i.e., a viral vector comprising only viral DNA/RNA) is not well established in the art, as isoelectric focusing is largely performed on proteins, rather than nucleic acids. This is because, chemically and structurally, proteins are susceptible to separation by pH gradients due to the variety of exposed amino acids with differing pIs. The acid in nucleic acids is typically only phosphate, which forms the phosphate backbone in DNA, such that SDS electrophoresis is much more suitable for separating nucleic acid molecules. Gel isoelectric focusing of transfer RNA (tRNA) and oligonucleotides is known in Drysdale et al. (“Fractionation of Nucleic Acids by Isoelectric Focusing,” 1972, Biochemistry, vol. 11, pgs. 4044-4051); however, tRNA and oligonucleotides are not analogous to viral vectors free of a capsid. Thus, the result of applying cIEF to a viral vector free of capsid is unpredictable.
(F) and (G) The amount of direction provided by the inventor and the existence of working examples:
Regarding the definition of a viral vector free of capsid, the instant specification only discloses in para. [0039]: “a ‘viral vector’ refers to a viral construct (e.g., viral molecule comprising one or more of DNA, RNA, or protein) used as a vehicle to harbor or carry foreign genetic material (i.e., an exogenous polynucleotide) into another cell where it can be replicated and/or expressed.” However, exemplary viral vectors and working examples in the specification only provide viral vectors with capsid proteins (“Exemplary viral vectors include retroviruses, lentiviruses, adenoviruses, adeno-associated viruses (AAV), and hybrids that are genetically modified to have qualities of more than one vector” in para. [0039] and the “empty” and “full capsids” in Table 1). The instant specification does not provide a standard for ascertaining a viral vector free of capsid. Since no working examples or guidance is provided for a viral vector free of capsid, one of ordinary skill in the art would have to speculate what constructs would fall within this definition.
Regarding the application of cIEF to a viral vector free of capsid, the instant specification only discloses in para. [0048]: “the cIEF method disclosed herein can separate and distinguish viral vectors as having a full length exogenous polynucleotide, having an exogenous polynucleotide fragment, or lacking any exogenous polynucleotide, based on the pI of each viral vector.” While this statement, taken in combination with the definition of “viral vector” in para. [0039], could be interpreted to mean that the disclosed cIEF method separates viral vectors comprising one or more of DNA and RNA but not protein, the working examples provided only detail viral vectors with capsid protein (see “empty” and “full capsids” in Table 1). Since no working examples or guidance is provided for the application of cIEF to a viral vector free of capsid, one of ordinary skill in the art would have to speculate how to perform cIEF on a viral vector free of capsid.
(H) The quantity of experimentation needed to make or use the invention based on the content of the disclosure: For the reasons discussed above, which in sum, are that the instant application does not provide working examples or guidance as to the application of cIEF to a viral vector sample free of capsid, use of the invention would require undue experimentation and so is not enabled.
Claims 1-9 and 11 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.
As rejected above, regarding the 112(a) scope of enablement, the scope of claim 1 covers “performing capillary isoelectric focusing (cIEF) on the sample comprising viral vectors containing exogenous polynucleotide… wherein the viral vectors are free of a capsid.” However, the instant specification does not provide proper written description for applying cIEF to viral vectors free of a capsid. As discussed previously, this would require a viral vector free of a capsid, working examples of which are not provided in the instant specification. Therefore, one of ordinary skill in the art would not know what comprises the sample or how to perform cIEF on such a sample. The instant specification provides no working examples or guidance regarding the application of cIEF to a viral vector sample free of capsid. Therefore, 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 at the time the application was filed, had possession of the broadly claimed invention. Claims 2-9 and 11 are further rejected by virtue of their dependence upon and because they fail to cure the deficiencies of claim 1 regarding a viral vector free of a capsid.
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 1-9 and 11 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.
Claim 1 states “performing capillary isoelectric focusing (cIEF) on the sample comprising viral vectors containing exogenous polynucleotide… wherein the viral vectors are free of a capsid.” However, the instant specification does not provide proper written description for a viral vector free of capsid. The ordinary meaning of “viral vector” in the art is “DNA or RNA surrounded by a capsid” (see pg. 293, col. 2, para. 3 in Laporte et al. [“Matrices and scaffolds for DNA delivery in tissue engineering,” 2007, Advanced Drug Delivery Reviews, vol. 59, pgs. 292-307]). Thus, the examiner is directed to the instant specification to determine the intended meaning of “viral vector,” wherein the applicant acts as their own lexicographer in cases where terms are used in a manner contrary to or inconsistent with one or more of their ordinary meanings (see MPEP 2173.05(a)(III)). The instant specification states in para. [0039]: “a ‘viral vector’ refers to a viral construct (e.g., viral molecule comprising one or more of DNA, RNA, or protein) used as a vehicle to harbor or carry foreign genetic material (i.e., an exogenous polynucleotide) into another cell where it can be replicated and/or expressed.” However, it is unclear what structures would form a viral vector free of capsid in light of this definition, as only DNA/RNA forming a structure around an exogenous polynucleotide is not a known viral vector in the art. Additionally, the viral “vehicle” is explicitly separate from the “foreign genetic material.” Thus, only separating the foreign genetic material via cIEF is not disclosed in the instant specification. Claims 2-9 and 11 are further rejected by virtue of their dependence upon and because they fail to cure the deficiencies of indefinite claim 1.
Claim 4 states “wherein the viral vectors are adeno-associated virus vectors.” This contradicts the limitation “wherein the viral vectors are free of a capsid” in claim 1 upon which claim 4 depends, as AAVs inherently include capsid proteins (see Table 1 and para. [0049] of the instant specification). Thus, it is unclear what AAV would fall within the scope of claim 4 in light of claim 1.
Claim 11 states “wherein the viral vectors are adeno-associated virus vectors.” This contradicts the limitation “wherein the viral vectors are free of a capsid” in claim 1 upon which claim 11 depends, as AAVs inherently include capsid proteins (see Table 1 and para. [0049] of the instant specification). Thus, it is unclear what AAV would fall within the scope of claim 11 in light of claim 1.
Response to Arguments
Applicant's arguments, see Remarks pgs. 1-5, filed 8/15/2025, with respect to the 35 U.S.C. § 103 rejections have been fully considered. All 35 U.S.C. § 103 rejections from the previous office action are withdrawn in view of the Applicant’s amendments.
Applicant’s arguments with respect to the 35 U.S.C. § 103 rejections are moot as they do not pertain to the current grounds of rejection for claims 1-9 and 11 under 35 U.S.C. § 112(a) and 112(b) above.
Conclusion
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 KAYLEE Y TSENG whose telephone number is (703)756-5542. The examiner can normally be reached Mon - Fri 9-6 PT.
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/K.T./Examiner, Art Unit 1795
/LUAN V VAN/Supervisory Patent Examiner, Art Unit 1795