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 .
Election/Restrictions
Applicant’s election without traverse of IRAK-4, and dendritic cells in the reply filed on 11/11/15 is acknowledged.
It is noted that the claims have been clarified/amended to exclusively identify the IRAK degrader of the claims an IRAK-4 degrader.
Status of the Claims
Applicant’s amendment submitted 11/11/25 is acknowledged. Claims 1-4,7,9-13,16,18,22-23,27,32 and 34-39 are pending.
Priority
The application claims the benefit of priority to US Provisional 63/330,245, filed 4/12/22.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 9/11/23 and 11/11/25 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements have been considered by the examiner.
Specification
The lengthy specification has not been checked to the extent necessary to determine the presence of all possible minor errors. Applicant’s cooperation is requested in correcting any errors of which applicant may become aware in the specification.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-4,7,9-13,16,18,22-23,27,32 and 34-39 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-13, 15, 17, 18, 33, 38, 39, 48 and 60 of copending Application No. 18/299,632 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other.
Both applications claim methods of delivering nucleic acid therapy, improving gene therapy, suppressing immune response, and selecting an individual for treatment with gene therapy, relying on the same steps and gene therapy component administered, however the claims of ‘632 are broader in scope for the IRAK degrader, specifically identifying the instantly claimed compound of formula I as one of 3 options in claim 11. Claims such as claims 7, 9, and 60 identify that the IRAK degrader/modulator targets IRAK-4. It would have been obvious to have used the specifically enumerated (and instantly claimed) IRAK-4 degrader compound of claim 11 in ‘632 in the methods because it is specifically identified for use and would be expected to perform as claimed.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claim Rejections - 35 USC § 112
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 7 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. As amended, claim 7 is no longer limiting because all claims are drawn to IRAK-4 degraders, and to a single compound of Formula (I), and the function/activity claimed in claim 7 would be inherent to the compound and does not limit the compound structurally. Effectively, the amendment to the claims has incorporated claim 7 into the base claim 4. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
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.
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.
Claim(s) 1-4, 7, 9, 16, 23 and 27 are rejected under 35 U.S.C. 103 as being unpatentable over KYMERA (US 2021/0323952 A1) in view of KNIGHT (US 10851349 B1).
The claims are drawn generally to treatments of gene therapy/gene delivery in combination with an IRAK-4 degrader of formula [I]. each method requires the same steps – administer the IRAK-4 degrader of Formula (I) and a gene therapy agent. KYMERA claims a method of treating an IRAK-mediated disorder (claim 24) and teaches the compound instantly claimed in the specification, for example [4476].
KYMERA teaches compounds that degrade and/or inhibit IRAK kinases (IRAK-1, IRAK-2, IRAK-4) for therapeutic use in patients, including oral administration formulations and routes such as oral, IV, and parenteral [1363–1366], [1350], [1359], [1343–1346] and preferred dosage is formulated so that 0.01–100 mg/kg body weight/day of the compound can be administered; regimen depends on patient factors and physician judgment [1360]–[1361]. The compounds are formulated with pharmaceutically acceptable carriers (e.g., salts, buffers, fixed oils), and dosage forms include tablets, capsules, solutions, suspensions, suppositories, topical creams/ointments, ophthalmic solutions/ointments, nasal aerosols/inhalation, and transdermal patches [1343]–[1358].
The compounds are useful for treating IRAK-mediated diseases, including cancers (hematologic and solid), autoimmune and inflammatory disorders, respiratory diseases (e.g., asthma, COPD), dermatologic, gastrointestinal, cardiovascular, neurological/neurodegenerative, metabolic, infectious/immunodeficiency, transplantation-related conditions, and bone/joint disorders [1372]–[1379], [1380]–[1391], [1393]–[1395], [1397], [1470], [1376], [1384]–[1389], [1390]–[1393]. KYMERA expressly teaches combination therapy: compounds “may be administered in combination with” one or more additional therapeutic agents appropriate for the disease; co-administration may be simultaneous or sequential; and mixed single-dosage compositions are contemplated [1408]–[1411], [1414]–[1419]. Example combination partners include small molecules, biologics, monoclonal antibodies, and nucleic-acid therapeutics (e.g., siRNA), with extensive, indication-specific lists (e.g., gout, RA, IBD, asthma/COPD, HIV, DLBCL, multiple myeloma) [1412]–[1413], [1420]–[1449], [1454]–[1469], [1471].
KYMERA provides methods of treatment of IRAK-mediated disorders (claims 24-28), where the disorder is, for example, lymphomas and leukemias.
While KYMERA provides guidance to combine with additional agents, including nucleic-acid therapeutics (e.g. siRNA), it does not teach the combination of with a gene therapy agent.
KNIGHT teaches (col 1, lines 5-23), “Nucleic acid therapeutics encapsulated in viral vectors hold great hope for many diseases, especially those of point mutations or monogenic disorders, many designated as orphan diseases. In November 2017, successful clinical trials were announced for AveXis® (Avexis Corp., Dallas, Tex.) gene therapy for spinal muscular atrophy type 1 disease in infants. The AAV-based therapy injected a healthy copy of the SMN1 gene. Approval is on the way for LUXTURNA® (Spark Therapeutics, Philadelphia, Pa.), a genetic therapy treatment for blindness, and Biomarin with Spark has a therapy for hemophilia. Earlier in the year, there were FDA approvals of Kymriah (Novartis, Basel, CH) which treats leukemia and YESCARTA® (Kite Pharma, Santa Monica, Calif.) which treats a form of lymphoma. There are 300 trials ongoing on in the industry. The therapeutic potential is even broader, applicable for common conditions of infectious disease, cancer and addictive disorders.
As set forth in In re Kerkhoven, 205 USPQ 1069 (CCPA 1980), “It is prima facie obvious to combine two compositions each of which is taught by prior art to be useful for same purpose in order to form third composition that is to be used for very same purpose; the idea of combining them flows logically from their having been individually taught in prior art.”
Here, KYMERA teaches the compound of instant formula I is useful for treating lymphomas and leukemias and KNIGHT teaches Kymriah and YESCARTA for treating leukemia and lymphoma. Thus, it flows logically from the art that it would have been obvious to have combined the compounds to form a third compound for the very same purpose and use it in the treatment of leukemias and lymphomas. With regards to the instant claim preambles, in the treatment of lymphoma or leukemia, the active steps- administer the compounds- is met, and one necessarily delivers nucleic acid to a cell (claim 1), treats an individual (claim 2), improves gene therapy (claim 3), and suppresses an immune response to gene therapy (claim 4).
Claim(s) 1-4, 7, 9-11, 23, and 27 are rejected under 35 U.S.C. 103 as being unpatentable over KYMERA (US 2021/0323952 A1) in view of TAK (US 8529885 B2).
The teachings of KYMERA are above. Kymera teaches that the compounds are used the treatment of rheumatoid arthritis [1375].
TAK teaches, “Surprisingly it was found that transduction efficacy of vectors based on of different AAV serotype virions in experimental models of rheumatoid arthritis varied considerably, ranging from being completely ineffective to having a very high transduction efficiency (for vectors contained in AAV5 virions). The Examples clearly demonstrate that in vivo gene transfer with AAV5 virions was far more efficient than with the other serotypes and that rAAV5 virion is particularly suited for in vivo gene therapy of rheumatoid arthritis” (col 16, lines 16-24). TAK further teaches a method for increasing expression of a therapeutic protein in a joint of a subject with rheumatoid arthritis (RA) consisting of the step of delivering a recombinant AAV5 (rAAV5) virion to a rheumatoid synovial cell in a joint of a subject with RA by injection into the joint, which virion consists essentially of the following components: (a) a capsid protein of AAV serotype 5 (AAV5), and (b) a recombinant adeno-associated virus type 2 (rAAV2) vector comprising a nucleotide sequence encoding a therapeutic protein to which is operably linked a promoter and expression elements; wherein an injection of said rAAV5 virion into said joint results in transduction of the synovial cell and an increase in expression of said therapeutic protein in said subject compared to expression following an injection of an equivalent dose of a virion that comprises (i) said rAAV2 vector of (b) and (ii) an AAV2 capsid protein in a second subject with RA. (claim 1).
As set forth in In re Kerkhoven, 205 USPQ 1069 (CCPA 1980), “It is prima facie obvious to combine two compositions each of which is taught by prior art to be useful for same purpose in order to form third composition that is to be used for very same purpose; the idea of combining them flows logically from their having been individually taught in prior art.”
Here, KYMERA teaches the compound of instant formula I is useful for treating RA, as does TAK, and thus it flows logically from the art that one would combine the two compounds to form a third compound for treating RA and use it in the treatment of RA with the expected outcome that it would treat RA. As above, with regards to the instant claim preambles, in the treatment of RA, the active steps- administer the compounds- is met, and one necessarily delivers nucleic acid to a cell (claim 1), treats an individual (claim 2), improves gene therapy (claim 3), and suppresses an immune response to gene therapy (claim 4).
Claim(s) 1-4, 7, 9-11, 13, 23, and 27 are rejected under 35 U.S.C. 103 as being unpatentable over KYMERA (US 2021/0323952 A1) in view of GAO (US 2008/0075740 A1).
The teachings of KYMERA are above. Kymera teaches that the compounds are used the treatment of rheumatoid arthritis and other diseases/conditions [1375+].
GAO teaches the use of an AAV viral vector, such as an AAV8 capsid, having an ITR (claim 7) where the ITR is from AAV2 (claim 8), in the treatment of diseases, such as RA, MS, and others (claim 4), [00115].
As set forth in In re Kerkhoven, 205 USPQ 1069 (CCPA 1980), “It is prima facie obvious to combine two compositions each of which is taught by prior art to be useful for same purpose in order to form third composition that is to be used for very same purpose; the idea of combining them flows logically from their having been individually taught in prior art.”
Here, KYMERA teaches the compound of instant formula I is useful for treating RA, as does GAO, and thus it flows logically from the art that one would combine the two compounds to form a third compound for treating RA, or other conditions, and use it in the treatment of RA and other conditions with the expected outcome that it would treat RA. As above, with regards to the instant claim preambles, in the treatment of RA, the active steps- administer the compounds- is met, and one necessarily delivers nucleic acid to a cell (claim 1), treats an individual (claim 2), improves gene therapy (claim 3), and suppresses an immune response to gene therapy (claim 4).
Claim(s) 1-4, 7, 9-11, 13, 16, 18, 22, 23, and 27 are rejected under 35 U.S.C. 103 as being unpatentable over KYMERA (US 2021/0323952 A1) in view of GREENBERG (US 2018/0258424 A1).
The teachings of KYMERA are above. Kymera teaches that the compounds are used the treatment of rheumatoid arthritis and other diseases/conditions [1375+].
GREENBERG teaches an adenoviral vector (claim 103), a lentiviral vector (claim 104), where the lentiviral is HIV (claim 105), where the AAV comprises one or more AAV2 ITRs, and where the composition is a nanoparticle (claim 117). The composition is used to treat various conditions such as RA, HIV, MS, Parkinson’s, and others (claims 127-130, and 134).
As set forth in In re Kerkhoven, 205 USPQ 1069 (CCPA 1980), “It is prima facie obvious to combine two compositions each of which is taught by prior art to be useful for same purpose in order to form third composition that is to be used for very same purpose; the idea of combining them flows logically from their having been individually taught in prior art.”
Here, KYMERA teaches the compound of instant formula I is useful for treating the same conditions as GREENBERG, and thus it flows logically from the art that one would combine the two compounds to form a third compound for treating any of the conditions such as RA, MS or Parkinson’s, or other conditions, and use it in the treatment with the expected outcome that it would treat the condition. As above, with regards to the instant claim preambles, in the treatment of the conditions, the active steps- administer the compounds- is met, and one necessarily delivers nucleic acid to a cell (claim 1), treats an individual (claim 2), improves gene therapy (claim 3), and suppresses an immune response to gene therapy (claim 4).
Claim(s) 1-4, 7, 9-13, 16, 18, 23, and 27 are rejected under 35 U.S.C. 103 as being unpatentable over KYMERA (US 2021/0323952 A1) in view of O’RIORDAN (US 2020/0216848 A1).
The teachings of KYMERA are above. Kymera teaches that the compounds are used the treatment of rheumatoid arthritis and other diseases/conditions [1375+] such as Huntington’s [1391].
O’RIORDAN teaches treating Huntington’s (claim 65) with an AAV2-HBKO viral particle (e.g. claim 122) or an AAV2 ITR (claim 126) and is a lentiviral particle (113)
Here, both KYMERA and O’RIORDAN teach their respective compounds are useful for treating Huntington’s, and thus it flows logically from the art that they would be combined to form a third composition for treating Huntington’s , and use it in the treatment with the expected outcome that it would treat the condition. As above, with regards to the instant claim preambles, in the treatment of the conditions, the active steps- administer the compounds- is met, and one necessarily delivers nucleic acid to a cell (claim 1), treats an individual (claim 2), improves gene therapy (claim 3), and suppresses an immune response to gene therapy (claim 4).
Art of Record
The following art is of relevance to the state of the art and understanding of the invention, but not relied upon for any rejection:
KASPAR (US 10695548 B1) provides the background that there are “7000 known monogenic disorders, approximately 2000 affect the skin.” (Background, col 1, lines 14-15).
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Andrew D Kosar whose telephone number is (571)272-0913. The examiner can normally be reached Monday-Friday, 7am-3:30pm.
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/Andrew D Kosar/Supervisory Patent Examiner, Art Unit 1625