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 1-5, 7-11, 13-16, 18-20, 22, 28, and 40 are pending.
Priority
Claims 1-5, 7-11, 13-16, 18-20, 22, 28, and 40 are a CON of PCT/US 2022/011239 filed on January 5, 2022, which has priority to PRO 63/134,139 filed on January 5, 2021.
Claim Objections
Claim 9 is objected to for the following reasons:
Claim 9 recites “at least one month, two month or three months” should read “at least one month, two months or three months”.
Claim Rejections - 35 USC § 112
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, 2, 3, 9, 10, 18, and 40 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.
Regarding claim 1, the phrase "such as" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d). The phrase is found in both part (a) and part (b) and part (3).
A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, claim 1 recites the broad recitation “at least one month”, and the claim also recites “or two months” which is the narrower statement of the range/limitation. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
Regarding claim 2, the phrase "such as" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, claim 2 recites the broad recitation “at least one month”, and the claim also recites “two months or three months” which is the narrower statement of the range/limitation. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
Regarding claim 3, the phrase "such as" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, claim 3 recites the broad recitation “at least one month”, and the claim also recites “two months or three months” which is the narrower statement of the range/limitation. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
Regarding claim 9, the phrase "such as" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, claim 9 recites the broad recitation “at least one month”, and the claim also recites “two months or three months” which is the narrower statement of the range/limitation. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
Regarding claim 10, the phrase "such as" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d). The phrase is found in both part (a) and part (b).
Regarding claim 18, the phrase "such as" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, claim 40 recites the broad recitation “greater than or equal to 1:1”, and the claim also recites “1:1.2, 1:1.5, 1:2, 1:3, 1:5, 1:7 or 1:10” which is the narrower statement of the range/limitation. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
Claim Rejections - 35 USC § 102
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.
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.
Claim 1, 5, 8, 9, 10, 11, 15, 16, 18, 22, and 28 are rejected under 35 U.S.C. §102(a)(1) as being anticipated by Meliani et al. [Antigen-selective modulation of AAV immunogenicity with tolerance rapamycin nanoparticles enables successful vector re-administration, Nature Communications, 2018].
Regarding claim 1, Melaini et al. teaches (1) a first dosing that comprises concomitantly administering [Abstract] (a) a viral vector, such as an AAV vector, that is not attached to any synthetic nanocarriers [Abstract], and (b) synthetic nanocarriers that are attached to an immunosuppressant, such as rapamycin, and that comprise no viral vector antigen-presenting (APC) presentable antigens of the viral vector [Methods; SVP[Rapa] nanoparticles production ¶ 1]; (2) a second dosing that comprises administering (c) the synthetic nanocarriers that are attached to an immunosuppressant and that comprise no viral vector APC antigens of the viral vector and without concomitant administration of the viral vector or concomitantly the synthetic nanocarriers that are attached to an immunosuppressant and that comprise no viral vector APC antigens of the viral vector and the viral vector, wherein the viral vector is at a dose lower than the dose of the viral vector of the first dosing [SVP[Rapa] control memory T cell responses to AAV ¶ 1]; and (3) administering the first and second dosings to a subject according to an administration schedule that reduces an undesired humoral immune response to the viral vector and/or increases transgene or nucleic acid material expression or provides durable transgene or nucleic acid material expression, such as for at least one month or two months from the first dosing [Id.].
For claim 5, Meliani et al. teaches the method of claim 1, wherein the second dosing is about a month after the first dosing [SVP[Rapa] permits AAV vector re-dosing in nonhuman primates ¶ 1].
For claim 8, Meliani et al. teaches the method of claim 1, wherein the administering of the first dosing, second dosing and/or third dosing is by intravenous administration [Fig. 1].
For claim 9, Meliani et al. teaches the method of claim 1, wherein the method further comprises identifying the subject as having a risk or at risk of having an undesired humoral immune response to the viral vector and/or as being in need of effective or durable transgene or nucleic acid material expression, such as for at least one month, two month[s] or three months [Abstract, Introduction ¶ 1].
For claim 10, Meliani et al. teaches a composition comprising: (1) one or more first doses that each comprise (a) a viral vector, such as an AAV vector, that is not attached to any synthetic nanocarriers [Abstract, Introduction ¶ 1], and/or (b) synthetic nanocarriers that are attached to an immunosuppressant, such as rapamycin, and that comprise no viral vector antigen-presenting cell (APC) presentable antigens of the viral vector [SVP[Rapa] nanoparticle production ¶ 1], wherein the one or more first doses in combination comprise (a) and (b); and (2) one or more second doses and, optionally, one or more third doses that each comprise (c) the synthetic nanocarriers that are attached to an immunosuppressant that comprise no viral vector APC presentable antigens of the viral vector and without a viral vector or (i) the synthetic nanocarriers that are attached to an immunosuppressant that comprise no viral vector APC presentable antigens of the viral vector and/or (ii) the viral vector, wherein the viral vector is at a dose lower than the one or more first doses, wherein the one or more second doses and/or on or more third doses in combination comprise (i) and (ii) [SVP[Rapa] control memory T cell responses to AAV ¶ 1]; optionally, for use in the method of reducing an undesired humoral immune response to the viral vector and/or increasing transgene or nucleic acid material expression or providing durable transgene or nucleic acid material expression, wherein the method comprises administering the first dose and second doses and, optionally, third doses to a subject according to an administration schedule [Id.].
For claim 11, Meliani et al. teaches the composition of claim 10, wherein the method further comprises determining that administration schedule for the first and second dose and, optionally, third doses that reduce an undesired humoral immune response to the viral vector and/or increase transgene or nucleic acid material expression or provides durable transgene or nucleic acid material expression [Fig. 5].
For claim 15, Meliani et al teaches the method of claim 1, wherein the immunosuppressants comprise a statin, an mTOR inhibitor, a TGF-B signaling agent, a corticosteroid, an inhibitor of mitochondrial function, a P38 inhibitor, an NF-KB inhibitor, an adenosine receptor agonist, a prostaglandin E2 agonist, a phosphodiesterase 4 inhibitor, and HDAC inhibitor or a proteasome inhibitor [Abstract].
For claim 16, Meliani et al. teaches the method of claim 1, wherein the immunosuppressant is an mTOR inhibitor [Abstract].
For claim 18, Meliani et al. teaches the method of claim 1, wherein the viral vector is an AAV vector, such as an AAV8 vector [SVP[Rapa] treatment allows for AAV vector re-administration ¶ 1].
For claim 22, Meliani et al. teaches the method of claim 1, wherein the synthetic nanocarriers are polymeric synthetic nanocarriers [SVP[Rapa] nanoparticle production ¶ 1].
For claim 28, Meliani et al. teaches the method of claim 1, wherein the mean particle size distribution obtained using dynamic light scattering of the synthetic nanocarriers of the population is a diameter greater than 100nm [SVP[Rapa] nanoparticle production ¶ 1].
Claim Rejections - 35 USC § 103
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.
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, 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 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.
Claims 2, 3, 4, 7, 19, 20, and 40 are rejected under 35 U.S.C. §103 as being unpatentable over Meliani et al. [Antigen-selective modulation of AAV immunogenicity with tolerogenic rapamycin nanoparticles enables successful vector re-administration, Nature Communications, 2018], in view of Ilyinskii and Kishimoto (Hereinafter Kishimoto) [US 2018 0193482 A1, 2018], in view of Chandler and Vendetti (Hereinafter Chandler) [Gene therapy for methylmalonic acidemia: past, present, and future, Hum Gene Ther., 2019].
Meliani et al. teaches every element of claim 1. However, Meliani et al. does not teach the addition of a third dose as found in claim 2.
For claim 2, Meliani et al. teaches every element of claim 2 except where the method comprises administering a third dose that is similar to the second dose where the dosage amount is lower than the initial dose. However, it would have been prima facie obvious to a person of ordinary skill in the art prior to the filing of the claimed invention to modify the systems and methods of Meliani et al. where a first and second dose was administered with the second dose being lower than the first dose. It would have been obvious for an artisan to administer third dose under the same parameters as the second dose given that repeat dosing is a common strategy in gene therapy that allows sustained gene expression. It also would have been prima facie obvious to a person of ordinary skill that repeated lower doses of the synthetic nanocarrier coupled with an immunosuppressant, i.e. rapamycin, would be given in the same manner given that immunosuppressants are typically administered with a load dose in order to achieve therapeutic efficacy followed by lower doses acting as maintenance doses. Because of this, there is a reasonable expectation of success that an artisan would understand the teachings of Meliani et al. that a third or multiple doses following the lower second dose could be administered at or lower than the second dose in order to maintain transgene expression as well as immune suppression in order to prevent a humoral immune response due to administering a viral vector.
For claim 3 where the administration schedule of the first and second doses are determined, Meliani et al. teaches the administration of AAV8 vector encoding secreted human embryonic alkaline phosphatase together with SVP[Rapa] or SVP[empty] (control group) were given a second treatment at or around 93 days [Results ¶ 1].
For claim 4 where the dosing is less than but at least 1/10 of the dose of the first viral vector of the first dosing, Meliani et al. teaches that the C57BL/6 mice received an initial dose of AAV8-Luc vector at a dose of 2 x 1012 vgkg-1 and a second dose of 4 x 1011 vgkg-1 on day 77 which is roughly 1/5 of the dose of the initial, i.e. first, dose [SVP[Rapa] control memory T cell responses to AAV ¶ 1].
For claim 7 where the method of claim 2 comprises assessing the undesired humoral immune response, Meliani et al. teaches that T cell responses with the control AAV8-Luc with SVP[Rapa] were analyzed for anti-AAV8 IgG antibodies [Fig. 5].
Here, it would have been prima facie obvious to a person of ordinary skill in the art prior to the filing of the claimed invention to modify the systems and methods of Meliani et al. where viral vectors and synthetic nanoparticles carrying rapamycin were co-administered to mice for first and second dosing and then analyzed in order to determine the presence of a humoral immune response. Given this, there is a reasonable expectation of success that a person of ordinary skill would recognize the teachings of Meliani et al. to conduct multiple dosings of viral vectors in conjunction with synthetic nanoparticles carrying an immunosuppressant and then analyze the treated subjects for any evidence of a humoral immune response or lack of a response to determine the efficacy of the concomitant of viral vector and synthetic nanoparticles carrying an immunosuppressant that results in suppressed immune response to the presence of a viral vector and/or enhances gene expression through mitigating interference from the host’s immune response.
For claim 13 where the method of claim 10 is included in a kit, Kishimoto describes the use of kits for both the viral vectors and synthetic nanocarriers that comprise an immunosuppressant [¶ 0034-0038].
For claim 14 where the method of claim 10 further contains a pharmaceutically acceptable carrier, Kishimoto discloses that a pharmaceutically acceptable carrier or excipient would be included and is made up of a pharmacologically inactive material used with a pharmacologically active material that can include materials such as saccharides, antimicrobial agents, reconstitution aids, colorants, saline, and buffers [¶ 0093].
Given this, it would have been prima facie obvious to a person of ordinary skill prior to the filing of the claimed invention to modify the systems and methods of Meliani et al. where viral vectors and synthetic nanoparticles carrying rapamycin were co-administered to mice for first and second dosing and then analyzed in order to determine the presence of a humoral immune response with the additional teachings of Kishimoto to include an inactive pharmacological material, e.g. saline or buffers, as part of the composition and to include such composition in a kit capable of providing one or more of any of the predetermined dosage amounts. Here, there is a reasonable expectation of success that a person of ordinary skill in the art would combine the teachings of Meliani et al. with the additional teachings of Kishimoto to provide a kit that contains a predetermined dosage of a composition that includes both a viral vector and a separate synthetic nanoparticle with an immunosuppressant payload to be administered to a subject for purposes of expressing the viral vector transgene while inhibiting an immune response through the use of nanocarriers coupled with an immunosuppressant for reducing or inhibiting the humoral immune response in the subject.
For claim 19 where the viral vector is for treating methylmalonic acidemia, Chandler, discussing current and potential future gene therapy treatments for methylmalonic acidemia (MMA), discloses several viral vectors carrying a MMA murine model phenotype including dosing, promoter, and cDNA/mRNA [Table 1]. Chandler also discloses rAAV gene therapy in the Mmut -/- mice tested showed that the rAAV9 vector was able to utilize the identical cassette as in the rAAV8 gene, and that it, too, had a strong liver tropism as rAAV8 [Canonical Adeno-associated virus gene therapy ¶ 3]. Chandler also disclosed that rAAV9 was able to obtain hepatic Mmut expression with a sustained therapeutic benefit [Id.].
For claim 20 where the method of claim 1 where the load of immunosuppressant across the population of synthetic nanocarriers is between 0.1% and 50%, Kishimoto discloses that the load of the immunosuppressant comprised in the synthetic nanocarriers, on average across the synthetic nanocarriers, is between 0.1% and 50% (weight/weight) [¶ 0032].
For claim 40 where the method of claim 1 the nanocarriers have an aspect ratio that is greater or equal to 1:1, 1:1.2, 1:1.5, 1:2, 1:3, 1:5, 1:7 or 1:10, Kishimoto discloses that the aspect ratio of a population of synthetic nanocarriers is greater than 1:1, 1:1.2, 1:1.5, 1:2, 1:3, 1:5, 1:7 or 1:10 [¶ 0033].
It would have been prima facie obvious to a person of ordinary skill in the art to modify the systems and methods of Meliani et al. where viral vectors and synthetic nanoparticles carrying rapamycin were co-administered to mice for first and second dosing and then analyzed in order to determine the presence of a humoral immune response with the teachings of Chandler where the authors discussed the current and future trends of gene therapy, including the use of viral vectors, in the treatment of methymalonic acidemia with the further teachings of Kishimoto that discloses the preferred payload range for the nanocarriers and immunosuppressant along with the preferred aspect ratio, i.e. size and shape. Therefore, there is a reasonable expectation of success that a person of ordinary skill in the art would combine the teachings of Meliani et al. with the further teachings of Chandler and Kishimoto in order to select an appropriate means for a gene therapy application targeting methylmalonic acidemia that included the payload percentage of immunosuppressant to be delivered to the subject in order to inhibit or reduce the humoral immune response from the subject being exposed to a viral vector antigen and that the synthetic nanocarrier would consist of a certain aspect ratio in order to maximize payload capacity and contribute to cellular uptake, circulation/biodistribution, drug loading, and release.
The Supreme court has acknowledged:
When a work is available in one field of endeavor, design incentives and other market forces can prompt variations of it, either in the same field or a different one. If a person of ordinary skill can implement a predictable varition..103 likely bars its patentability…if a technique has been used to improve one device, and a person of ordinary skill in the art would recognize that it would improve similar devices in the same way, using the technique is obvious unless its actual application is beyond that person’s skill. A court must ask whether the improvement is more than the predictable use of prior-art elements according to their established functions…
…the combination of familiar elements according to known methods is likely to be obvious when it does no more than yield predictable results (see KSR International Co. v. Teleflex Inc., 82 USPQ2d 1385 U.S. 2007) emphasis added.
In KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398 (2007), the Supreme Court reaffirmed "the conclusion that when a patent 'simply arranges old elements with each performing the same function it had been known to perform' and yields no more than one would expect from such an arrangement, the combination is obvious." Id. at 417 (quoting Sakraida v. Ag Pro, Inc., 425 U.S. 273,282 (1976)). The Supreme Court also emphasized a flexible approach to the obviousness question, stating that the analysis under 35 U.S.C. § 103 "need not seek out precise teachings directed to the specific subject matter of the challenged claim, for a court can take account of the inferences and creative steps that a person of ordinary skill in the art would employ." Id. at 418; see also id. at 421 ("A person of ordinary skill is... a person of ordinary creativity, not an automaton.").
From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
Conclusion
No claims allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JOHN DAVID MOORE whose telephone number is (703)756-1887. The examiner can normally be reached M-F 8-5.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Tracy Vivlemore can be reached on 571-272-2914. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/JOHN DAVID MOORE/Examiner, Art Unit 1638
/Tracy Vivlemore/Supervisory Primary Examiner, Art Unit 1638