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
Claim status
Claims 1-4, 29, 33, 36, 42, 44-45, 53-62 are pending
Claims 1-4, 58-62 are withdrawn
Claims 29, 33, 36, 42, 44-45, 53-57 are under examination
Election/Restrictions
Applicant’s election of the following invention in the reply filed on 6/24/2026 is acknowledged.
Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.03(a)).
The requirement is still deemed proper and is therefore made FINAL.
Group II, claims 29, 33, 36, 42, 44-46, 53-57, drawn to compositions of recombinant viral vectors, pharmaceutical compositions, and kits thereof.
.
Claims 1-4, 58-62 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable linking claim.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 1/19/2024, 2/22/2024, and 1/27/2025 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
However, Applicant is reminded that the listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
Objection to Drawings
Figure 6 of the Specification is out of order and does not conform to standards as having ”numbered in consecutive Arabic numerals, starting with 1, independent of the numbering of the sheets and, if possible, in the order in which they appear on the drawing sheet(s)” (see also 37 CFR 1.84(u)).
Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 29, 33, 36, and 42 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Groendahl et al., (US2019/0255193, filed 10/27/2016, published 8/22/2019, with priority to GB1519086.1 filed 10/28/2015, see IDS filed 1/19/2024)
In regard to claims 29 and 33, Groendahl claims a recombinant AAV vector comprising a nucleotide sequence encoding factor I (see Claims 1 and 2 of priority document GB1519086.1). In regard to the functional effects, Groendahl teaches that complement factor I increases the level of C3b-inactivating and iC3b-degradation activity ([0102, 0107] of 2109/02555193, see also priority document GB1519086.1 p. 7, Factor I).
In regard claim 36, Groendahl teaches the AAV vector forms an AAV particle comprises capsid proteins that encapsulated the AAV vector comprising the nucleic acid encoding the Factor I transgene (0220] of 2109/02555193, see also priority document p.19, 8th para., p.22, 2nd para).
In regard to claim 42, Groendahl teaches the AAV vector is in a pharmaceutical composition with a pharmaceutically acceptable carrier, diluent or excipient (see Claim 10 of priority document, as well as p.28, 5th para., Pharmaceutical compositions and injected solutions).
Accordingly, Groendahl anticipates instant claims.
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 of this title, 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.
The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 44 and 45 are rejected under 35 U.S.C. 103 as being unpatentable over Groendahl et al., (US2019/0255193, filed 10/27/2016, published 8/22/2019, with priority to GB1519086.1 filed 10/28/2015), in view of Zhong (WO 2008/124724, filed 4/08/2008, published 10/16/2008)
As discussed previously, Groendahl teaches an AAV vector comprising a nucleic acid encoding Factor I.
In regard to claim 44, as stated supra, Groendahl teaches the AAV vector is in a pharmaceutical composition with a pharmaceutically acceptable carrier, diluent or excipient.
In regard to claim 45, Groendahl teaches the AAV vector is replication-deficient, and requires helper functions in trans for completion of a replication and packaging cycle (p. 19, 1st para. of priority document).
However, Groendahl et al is silent with respect to the AAV vectors in kits.
Nevertheless, Groendahl cites the prior art of Zhong (WO2008) as incorporated by reference (p.19, 8th para. of priority document).
Zhong teaches an rAAV vector for gene therapy purposes. Specifically, in regard to claim 44, Zhong teaches the rAAV vector is in a kit with a pharmaceutical composition for therapeutic purposes [0023, 0030, 0095, 0097]. In regard to claim 45, alternatively Zhong teaches the rAAV vector is in a kit for production methodologies
Accordingly, it would have been prima facie obvious to one of ordinary skill in the art at the time of filing to prepare compositions comprising the rAAV vector either as a pharmaceutical composition or with helper genes in trans as taught by Groendahl, and combine those elements into kits for therapy or kits for production as taught by Zhong with a reasonable expectation of success. The ordinary skilled artisan would have been motivated to do so because such kits were well known in the art at the time the invention was made. Therefore, it would have been obvious to combine said components into a kit for the purposes of convenience and economy. Furthermore, form of the use of plasmids which comprise the rep and cap genes was well known and obvious as being encompassed by the helper function genes as disclosed by Groendahl.
Hence, the claimed invention as a whole was prima facie obvious in the absence of evidence to the contrary.
Claims 53-55 are rejected under 35 U.S.C. 103 as being unpatentable over Groendahl et al., (US2019/0255193, filed 10/27/2016, published 8/22/2019, with priority to GB1519086.1 filed 10/28/2015)
As discussed previously, Groendahl teaches an AAV vector comprising a nucleic acid encoding complement factor I (Claims 1 and 2 of priority document).
In regard to claim 53, Gorendahl teaches the human complement factor I that is encoded by nucleic acid sequence SEQ ID NO: 2 ([0130] of 2019/0255193, see also Claim 2 of priority document GB1519086.1 p. 9), which corresponds to NM_000204 and is translated into the amino acid of SEQ ID NO:2 (see SCORE report 8/14/2026, rup file, result #2). In regard to the AAV vector pseudotyped to confer liver tropism, Groendahl teach the rAAV vector comprises an AAV8 capsid (see below), which is known to confer liver tropism.
In regard to claims 53-55, Groendahl teach the rAAV vector is an AAV2/8 vector ([0232] of 2019/0255193, see also priority document GB1519086.1 p. 24 line 24).
However, Groendahl is silent to a preferred embodiment of a AAV2/8 vector.
Nevertheless, it would have been obvious to one having ordinary skill in the art at the time the invention was filed to produce a AAV2/8 vector because each of the individual elements of the instant claims are independently presented by Groendahl as embodiments and are taught that they can be combined in various embodiments; therefore a combination of all the elements into a single embodiment would be apparent to an artisan skilled in gene therapy in light of the Supreme Court’s KSR decision (see MPEP 2143 Exemplary Rationale (A)). Regarding the rationale for combining prior art elements according to known methods to yield predictable results, all of the claimed elements were known in the prior art and one skilled in the art could have combined the element as claimed by known methods with no change in their respective functions, and the combination would have yielded predictable results to one of ordinary skill in the art at the time of the invention. Each of the elements (AAV2/8 vector, delivery methods and formulations) are taught by Groendahl and further they are taught in various combinations and are shown to be used in a method for producing rAAV. It would have been therefore predictably obvious to use a combination of these elements in said vector.
Hence, the claimed invention as a whole was prima facie obvious in the absence of evidence to the contrary.
Claims 29, 33, 36, and 42 are rejected under 35 U.S.C. 103 as being unpatentable over Lachmann (WO2010/103291, published 9/16/2010, see IDS filed 1/19/2024), in view of Song et al., (US2019/0177381, filed 9/23/2016, with priority to 62/232,008 filed 9/24/2015, see IDS filed 1/19/2024)
In regard to Claim 29, Lachmann teaches the cDNA for recombinant human complement factor I in order to raise the level of Factor I in a subject to treat disease linked to overactivity of the complement system (Abstract, p. 21, 2nd para.).
However, in regard to Claim 29, although Lachmann teaches that recombinant complement factor I is used therapeutically (p. 13, last para., p. 19, last para.), they are silent to a viral vector for the overexpression of recombinant human complement factor I in vivo. Nevertheless, expressing recombinant human complement factors in viral vectors for treating complement-mediated disorders were well known in the art.
In regard to instant claims, Song (US2019) teaches an rAAV vector encoding a recombinant human complement factor H protein ([0027-0028, 0033-0034, 0039-0040, 0043, 0047-0048] and Figs. 10-11, 15-16, 21, 22, 24, and 28-29 of 2019/0177381, see also 62/232,008 priority document p. 7, last para., p. 8, 2nd para., p. 9, 4th para., p. 10, 2nd para, p. 11 3rd & 4th para., p. 12, 2nd para., p. 39, 2nd para., and Fig. 10-11, 18, and 24-26). Much like complement factor I, Song teaches that complement factor H is a cofactor for complement factor I and works in the C3 breakdown pathway by increasing C3b-inactiving levels (see Fig. 7 of Song from the 62/232,008 priority document).
Accordingly, it would have been prima facie obvious to one of ordinary skill in the art at the time of filing to produce a cDNA for making a recombinant complement factor I for protein therapy of complement-mediated disorders as taught by Lachmann and combine the cDNA into a recombinant rAAV vector encoding the complement factor protein for gene therapy of complement-mediated disorders as taught by Song with a reasonable expectation of success. The ordinary skilled artisan would have been motivated to do so for several reasons. First, Song teaches that protein therapy requires large scale heterologous expression systems which require significant effort (see 62/232,008 priority document p. 3, last para.). Second, Song teaches that administered proteins have a quick clearance rate (note that Lachmann teaches that complement factor I protein has a plasma half-life of only a week) thereby making protein therapy cumbersome and less practical as multiple and frequent administrations of such protein drugs would be required (see 62/232,008 priority document pgs. 3-4 of Song). By contrast, Song teaches that compared to using the cDNA for recombinant protein therapy, AAV expression is preferred for efficiency and for convenience, where an AAV mediated gene-therapy expression of complement factor proteins can work for months (62/232,008 priority document see Fig. 23 of Song). Thus, it would have been obvious to combine the cDNA for protein therapy of Lachman into an rAAV vector for the gene therapy methods.
In regard to claims 33 and 36, as stated supra, Song makes obvious combining the human complement factor I cDNA into an rAAV, which forms a viral particle encapsulating the vector (see also 62/232,008 priority document p. 6, 5th para., p. 26, last para. to p.27, last para. of Song).
In regard to claim 42, Song teaches the rAAV is in a pharmaceutical composition with a physiologically acceptable carrier (62/232,008 priority document p. 28, last two para. of Song), which would have been obvious in order to safely administering the rAAV to a subject with a complement-disorder.
Hence, the claimed invention as a whole was prima facie obvious in the absence of evidence to the contrary.
Claims 53-54 and 56 are rejected under 35 U.S.C. 103 as being unpatentable over Lachmann (WO2010/103291, published 9/16/2010, see IDS filed 1/19/2024), in view of Ullman et al. (Mol Immuno, 1998, 35:503-512, see IDS filed 1/19/2024), Catterall et al. (Biochem J. 1987, 242:849-856, see IDS filed 1/19/2024), Song et al., (US2019/0177381, filed 9/23/2016, with priority to 62/232,008 filed 9/24/2015, see IDS filed 1/19/2024), and Nilsson et al., (Mol Immunology, 2011, 48:1611-1620, see IDS filed 1/19/2024)
In regard to Claim 53, Lachmann teaches the cDNA for recombinant human complement factor I in order to raise the level of Factor I in a subject to treat disease linked to overactivity of the complement system (Abstract, p. 21, 2nd para.).
However, Lachmann is silent to the sequence of the human complement factor I. Nevertheless, Lachmann references Ullman et al. (1998) for the recombinant overexpression of human complement Factor I (p. 21, 2nd para. of Lachmann). Ullman references Catterall et al. (1987) for the origin of the sequence (p. 504, Materials and methods of Ullman).
In regard to claim 53, Catterall teaches the cloning and characterization of human complement factor I from human liver tissue corresponding to an amino acid sequence that is 100% identical to SEQ ID NO:2 (see SCORE report 10/07/2021, rpr file, result #1).
Accordingly, it would have been prima facie obvious to one of ordinary skill in the art at the time of filing produce a recombinant human complement factor I for treating complement-mediated disorders in a subject, and choose the sequence of the human complement factor I protein corresponding to SEQ ID NO:2 as taught by Catterall with a reasonable expectation of success. The ordinary skilled artisan would have been motivated to do so because, as stated supra, Lachmann references the prior art that includes Catterall, thus out of convenience and common sense it would have been obvious to turn to the known human sequence for complement factor I that were being used for similar purposes of recombinant expression. Furthermore, the successful cloning and sequencing of the cDNA encoding a known protein is obvious, and thus unpatentable, if (1) there was some suggestion or motivation in the prior art to clone the cDNA, and (2) there was a “reasonable expectation of success,” based on "detailed enabling methodology" in the prior art. Ex parte Kubin, 83 U.S.P.Q.2d (BNA) 1410 (B.P.A.I. 2007), aff'd, 561 F.3d 1351 (Fed. Cir. 2009), which are provided by both Lachmann and Catterall.
However, in regard to Claim 53, although Lachmann teaches that recombinant complement factor I is used therapeutically (p. 13, last para., p. 19, last para.), they are silent to a viral vector for the overexpression of recombinant human complement Factor I in vivo. Nevertheless, expressing recombinant human complement factors in viral vectors for treating complement-mediated disorders were well known in the art.
In regard to instant claims, Song (US2019) teaches an rAAV vector encoding a recombinant human complement factor H protein ([0027-0028, 0033-0034, 0039-0040, 0043, 0047-0048] and Figs. 10-11, 15-16, 21, 22, 24, and 28-29 of 2019/0177381, see also 62/232,008 priority document p. 7, last para., p. 8, 2nd para., p. 9, 4th para., p. 10, 2nd para, p. 11 3rd & 4th para., p. 12, 2nd para., p. 39, 2nd para., and Fig. 10-11, 18, and 24-26). Much like complement factor I, Song teaches that complement factor H is a cofactor for complement factor I and works in the C3 breakdown pathway by increasing C3b-inactiving levels (see Fig. 7 of Song from the 62/232,008 priority document).
Accordingly, it would have been prima facie obvious to one of ordinary skill in the art at the time of filing to produce a cDNA comprising SEQ ID NO:2 for making a recombinant complement factor I for protein therapy of complement-mediated disorders as suggested by Lachmann et al. and combine the cDNA into a recombinant rAAV vector encoding the complement factor protein for gene therapy of complement-mediated disorders as taught by Song with a reasonable expectation of success. The ordinary skilled artisan would have been motivated to do so for several reasons. First, Song teaches that protein therapy requires large scale heterologous expression systems which require significant effort (see 62/232,008 priority document p. 3, last para.). Second, Song teaches that administered proteins have a quick clearance rate (note that Lachmann teaches that complement factor I protein has a plasma half-life of only a week) thereby making protein therapy cumbersome and less practical as multiple and frequent administrations of such protein drugs would be required (see 62/232,008 priority document pgs. 3-4 of Song). By contrast, Song teaches that compared to using the cDNA for recombinant protein therapy, AAV expression is preferred for efficiency and for convenience, where a AAV mediated gene-therapy expression of complement factor proteins can work for months or years (62/232,008 priority document see Fig. 23 of Song). Thus, it would have been obvious to combine the cDNA for protein therapy of Lachman into an rAAV vector for the gene therapy methods of Song.
However, although Lachmann teaches systemic administration of the recombinant complement factor I protein (p. 13, 2nd -5th para., see Claim 43 Lachmann), and Catterall teaches that human complement factor I cDNA was isolated from human liver tissue, they are silent to an AAV vector comprising the cDNA for human complement factor I being pseudotyped for liver tropism, and having a liver-specific promoter.
Nevertheless, in regard to claim 53, as well as claims 54 and 56, Song teaches that targeting the vector to the liver is desirable for maximizing expression of the secreted complement factor protein, and Song teaches doing so with an AAV8 pseudotyped vector, which is known to exhibit liver tropism, and a liver-specific promoter ([0027-0028, 0033-0034, 0039-0040, 0043, 0047-0048, 0080] and Figs. 10-11, 15-16, 21, 22, 24, and 28-29 of 2019/0177381, see also 62/232,008 priority document p. 7, last para., p. 8, 2nd para., p. 9, 4th para., p. 10, 2nd para, p. 11 3rd & 4th para., p. 12, 2nd para., p. 22, 3rd para., p. 39, 2nd para., and Fig. 10-11, 18, 24-26, and 33, see claims 15 and 16 of Song).
Accordingly, it would have been prima facie obvious to one of ordinary skill in the art at the time of filing to produce an AAV vector comprising a cDNA encoding recombinant human complement factor I of SEQ ID NO:2 as suggested by Lachmann et al., and choose an AAV8 vector with liver tropism and a liver-specific promoter as taught by Song with a reasonable expectation of success. The ordinary skilled artisan would have been motivated to do so for several reasons. First, as stated supra, Song teaches targeting the liver is desirable for maximizing expression of the serum secreted complement factor ([0080] of 2019/01777381; see also 62/232,008 priority document p. 22, lines 17-19). Furthermore, as stated supra, the cDNA for human complement factor I was cloned from human liver tissue, and the prior art review of Nilsson et al. (2011), teaches that complement factor I is a serum protein mainly synthesized in the liver (p. 1611, Abstract, Section 2). Thus, there would have been a reasonable expectation of success in overexpressing human complement factor I in the liver with an AAV8 vector with a tropism for human liver cells, and a liver specific promoter, since the cellular machinery of the human liver was equipped for expression of the human complement factor I gene.
Hence, the claimed invention as a whole was prima facie obvious in the absence of evidence to the contrary.
Claim 57 is rejected under 35 U.S.C. 103 as being unpatentable over Lachmann (WO2010/103291, published 9/16/2010, see IDS filed 1/19/2024), in view of Ullman et al. (Mol Immuno, 1998, 35:503-512, see IDS filed 1/19/2024), Catterall et al. (Biochem J. 1987, 242:849-856, see IDS filed 1/19/2024), Song et al., (US2019/0177381, filed 9/23/2016, with priority to 62/232,008 filed 9/24/2015, see IDS filed 1/19/2024), and Nilsson et al., (Mol Immunology, 2011, 48:1611-1620, see IDS filed 1/19/2024), as applied to claims 53 and 56, in further view of Hafenrichter et al. (Blood, 1994, 84:3394-404, see IDS filed 1/19/2024)
As stated supra, Lachmann et al. suggest a rAAV8 vector comprising a cDNA encoding human complement factor I protein of SEQ ID NO:2 operably linked to a liver specific promoter.
In regard to claim 57, Song suggests the liver specific promoter in humans is the alpha-1-anti-trypsin (AAT) promoter (see 62/232,008 priority document p. 22, lines 20 and 22).
Accordingly, it would have been prima facie obvious to one of ordinary skill in the art at the time of filing to produce a rAAV8 vector comprising a cDNA encoding human complement factor I protein operably linked to a liver specific promoter as suggested by Lachmann et al., and choose the human AAT liver specific promoter as suggested by Song with a reasonable expectation of success. The ordinary skilled artisan would have been motivated to do so for several reasons. First, Song teaches that the alpha-1-anti-trypsin (AAT) promoter from a limited genus of human liver specific promoters disclosed by Song because this would be applicable for expressing complement factors in the livers of humans. Furthermore, the prior art of Hafenrichter (1994) teaches among liver specific promoters tested for in vivo transduction of liver, the hAAT promoter resulted in the highest expression (Abstract, p. 3401, Table 2 & Fig. 5).
Hence, the claimed invention as a whole was prima facie obvious in the absence of evidence to the contrary.
Conclusion
No claims are allowed.
Examiner Contact Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ARTHUR S LEONARD whose telephone number is (571)270-3073. The examiner can normally be reached on Mon-Fri 9am-5pm.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, James Doug Schultz can be reached on 571-272-0763. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/ARTHUR S LEONARD/Examiner, Art Unit 1631
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