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 .
Priority
This is a National Stage Entry under 35 U.S.C. 371 of International Patent Application
No. PCT/EP2022/053477, filed February 14, 2022 and Foreign Patent Application, GB2102049.0, filed February 13, 2021.
Claim Objections
Claims 30 – 46 are objected to because of the following informalities:
Claim 30, the recitation of “characterised” should be amended to recite “wherein”
Claims 31 – 46, the recitation of “A group B adenovirus according to claim . . . ” should be amended to recite “The group B adenovirus according to claim . . . ”
Appropriate correction is required.
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.
Claim 35 is indefinite in their recitation of "wherein IL-12 has a sequence shown in SEQ ID NO: 115." It is unclear if the quoted phrase refers to the full length of the claimed sequence or a domain of the claimed sequence. The examiner interprets claim 35 as “A group B adenovirus according to claim 34, wherein IL-12 comprises the sequence of SEQ ID NO:115.”
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 31 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 30, on which claim 31 relies on, recites a “encodes a polypeptide comprising the sushi domain of IL-15R alpha, and does not comprise a transmembrane or GPI anchor such that it is not membrane anchored when expressed”. Claim 31 does not further limit any aspect of the polypeptide because it recites “the polypeptide encoding the sushi domain does not comprise a transmembrane domain or GPI anchor,” which does not limit the polypeptide or the sushi domain. 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
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.
Claims 30, 32, 34, 36 - 37, and 41 - 45 are rejected under 35 U.S.C. 103 as being unpatentable over Jia et al. (US 20190169253 A1, hereinafter, "Jia"), and in further view of Champion et al. (US 10124028 B2, hereinafter, “Champion”).
With regard to Claims 30, 34, and 37, Jia teaches an oncolytic herpes simplex viral vector comprising an expression cassette of one or more of IL-12, IL-15, and IL-15Ra (Abstract), with the IL-15Ra being limited to the sushi domain of IL-15Ra (¶ 0023, Figure 9A, reproduced below). As evidenced by Wei et al. (J Immunology, 2001), the sushi domain of IL-15Ra lacks a transmembrane component (Figure 1).
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Regarding claim 32, Jai teaches the sushi domain in the G4 position (Figure 13A, reproduced below.)
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Regarding claim 36, Jia teaches the IL-12 in the G2 position (Figure 5, reproduced below.)
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Regarding claim 41, Jia teaches the expression cassette can be one or more of IL-12, IL-15, and IL-15Ra (Abstract), which includes having only IL-12 and IL-15 resulting in m being 0.
Regarding claim 43, SEQ ID NO: 177 encodes for a polypeptide comprised of IL-12, IL-15Ra, and IL-15. Amino acids 1 - 549 correspond to IL-12, 550 – 567 correspond to a 2A peptide, and 568 – 810 correspond to IL-15Ra. Jia teaches an expression cassette of one or more of IL-12, IL-15, and IL-15Ra (Abstract). The overall structure and function of the protein is taught by Jia as an expression cassette of IL-12 and IL-15Ra is recited in the abstract. In this case, Figure 5 of Jia shows at least an IL-12 sequence followed by a 2A peptide that is upstream of IL-15Ra.
Furthermore, Wong et al. (US20200071374A1) teaches multi chain fusion polypeptide comprising of IL-12 fused to IL-15Ra sushi domain (Sequence 122, Page 142, ¶757). Notably, the IL-12 sequence, identified is “Query” has a 95.9% match with the IL-12 sequence of Wong, identified is “Sbjct” (reproduced below).
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The reference fails to teach the use of an adenovirus backbone, using a major late promoter to regulate transgene expression, a pharmaceutical carrier for the vector, or using the adenovirus to treat cancer.
However, Champion teaches using an oncolytic virus adenovirus that encodes either an insoluble or soluble variant of IL-15 (Col. 21, Line 36 - 40). With regards to the adenovirus backbone, the applicant has described the common backbone of an adenovirus (Figure 1), including a restriction site found at BX in Human Adenovirus 3 (Figure 2). As such, Singh et al. (Adenoviruses, 2018, hereinafter, Singh) describe an adenovirus comprising of E1A-E1B, followed by E2B-L1-L2-L3-L4, which is connected to E3, which in turn is connected to L5.
[AltContent: textbox ([img-media_image5.png]
Figure 1. Adenovirus structure. Singh (Adenoviruses, 2018))][AltContent: textbox ([img-media_image6.png]
Figure 2. mscI restriction site located at the beginning of L5. Lin et al. (Genome Res, 2006))]
Regarding claim 42, Champion teaches an oncolytic adenovirus with a major late promoter regulating transgene expression (Col 23, Line 58 - 65).
Regarding claim 44, Champion teaches pharmaceutical carriers of the oncolytic virus can be formulated with HEPES buffer (Col 40, Line 5 – 18).
Regarding claim 45, Champion teaches administering a therapeutically effective amount of adenovirus to treat cancer (Col. 42, Line 4 – 12).
Jia and Champion are both considered to be analogous to the claim invention because they are in the same field of treating cancer through oncolytic viruses. Therefore, it would have been prima facie obvious before the effective filing date of the claimed invention to utilize the art-recognized method to encode IL-15/IL-15Ra sushi domain chimeric protein, as demonstrated by Jia, within an adenovirus, as taught by Champion, because doing so would advantageously increase viral spread and activity, thereby increasing probability of affecting cancerous cells. One of ordinary skill in the art would have reasonable expectation of success in using different viral vector backbones to increase efficacy of cancer treatment given that this method is well known, has been successfully demonstrated, and commonly used in the prior art.
Accordingly, the claimed invention was prima facie obvious to one of ordinary skill in the art at the time of filing especially in the absence of evidence to the contrary.
Claims 33 , 38, 39, 40, and 46 are rejected under 35 U.S.C. 103 as being unpatentable over Jia and Champion as applied to claims 30, 32, 34, 36 - 37, and 41 - 45 above, and further in view of Ma et al. (US20210338729A1, hereinafter, "Ma").
As discussed above, claims 30, 32, 34, 36 - 37, and 41 - 45 were rendered prima facie obvious by the teachings of Jia and Champion. The references fail to teach encoding IL-2 leader sequence, at least one chemokine such as CCL-19 within an adenovirus backbone or the use of a virus in combination with cellular therapy.
However, regarding claim 33, Ma teaches that a polynucleotide for a chimeric antigen receptor (CAR) molecule can be comprised of an IL-2 leader sequence followed by IL-15/IL-15Ra sushi domain complex (¶272, 325), which can be cloned into an adenovirus vector (¶275).
Regarding claim 38, Ma teaches that the polynucleotide can be comprised of a chemokine (¶210).
Regarding claim 39, Ma teaches that the polynucleotide can be comprised of CCL-19 (¶210).
Regarding claim 40, Ma teaches the CCL-19 can be encoded in G3. (¶210).
Regarding claim 46, Ma teaches the use of viral vectors for cellular therapy (¶282 – 287).
Ma, Jia, and Champion are considered to be analogous to the claim invention because they are in the same field of treating cancer through oncolytic viruses. Therefore, it would have been prima facie obvious before the effective filing date of the claimed invention to utilize the art-recognized method to include an IL-2 leader sequence with a IL-15/IL-15Ra sushi domain, IL-12, and CCL-19, with positioning of CCL-19 downstream of the cytokines, and use the viral vector in combination with cellular therapy, as taught by Ma, with the method as taught by Jia and Champion, because doing so would advantageously increase viral spread and payload secretion efficiency, thereby increasing probability of affecting cancerous cells. One of ordinary skill in the art would have reasonable expectation of success in using different protein components for a chimeric antigen receptor protein to increase efficacy of cancer treatment given that this method is well known, has been successfully demonstrated, and commonly used in the prior art.
Accordingly, the claimed invention was prima facie obvious to one of ordinary skill in the art at the time of filing especially in the absence of evidence to the contrary.
Claim 35 is rejected under 35 U.S.C. 103 as being unpatentable over Jia and Champion as applied to claims 30, 34, 37, 42, 44, and 45 above, and further in view of Lieschke et al. (Nature Biotechnology, 1997, hereinafter, “Lieschke”).
As discussed above, claims 30, 32, 34, 36 - 37, and 41 - 45 were rendered prima facie obvious by the teachings of Jia and Champion. The references fail to teach encoding IL-12 sequence, described as a “single chain fusion protein… in the format p40-linker-p45… wherein the linker comprises one or more units of Gly4Ser” and as “mature human IL-12 p70 single chain protein with a (Gly4Ser)3 linker joining the IL12p40”.
However, regarding claim 35, Lieschke teaches the use of IL-12 fusion protein, known as IL-12.p40L▲p35, which is “comprised of the p40 subunit linked by a (Gly4Ser)3 linker to the p35 subunit” (Introduction: ¶2) that retain potent antitumor activity. Amino acids 1 – 306 of SEQ ID NO: 115 share a sequence similarity with IL-12.p40, 307 to 321 is a (Gly4Ser)3 linker and amino acids 322 – 517 share a sequence similarity with IL-12.p37. Together, SEQ ID NO: 115 shares the function and protein design as taught by Lieschke. Furthermore, this protein sequence is found in prior art such as in Winston et al. (US20190367576A1, hereinafter, “Winston”). SEQ ID NO: 115, identified is “Qy” has a 100% match with Winston, identified as “Db” (reproduced below), further
RESULT 3
US-16-438-166-45
(NOTE: this sequence has 14 duplicates in the database searched)
Sequence 45, US/16438166
Publication No. US20190367576A1
GENERAL INFORMATION
APPLICANT: WEREWOLF THERAPEUTICS, INC.
TITLE OF INVENTION: ACTIVATABLE INTERLEUKIN 12 POLYPEPTIDES AND METHODS OF USE
TITLE OF INVENTION: THEREOF
FILE REFERENCE: 105365-0027
CURRENT APPLICATION NUMBER: US/16/438,166
CURRENT FILING DATE: 2019-06-11
PRIOR APPLICATION NUMBER: PCT/US2019/032322
PRIOR FILING DATE: 2019-05-14
PRIOR APPLICATION NUMBER: 62/756,507
PRIOR FILING DATE: 2018-11-06
PRIOR APPLICATION NUMBER: 62/756,515
PRIOR FILING DATE: 2018-11-06
PRIOR APPLICATION NUMBER: 62/756,504
PRIOR FILING DATE: 2018-11-06
PRIOR APPLICATION NUMBER: 62/671,225
PRIOR FILING DATE: 2018-05-14
NUMBER OF SEQ ID NOS: 92
SEQ ID NO 45
LENGTH: 524
TYPE: PRT
ORGANISM: Artificial Sequence
FEATURE:
OTHER INFORMATION: Description of Artificial Sequence: Synthetic
polypeptide
Query Match 100.0%; Score 2741; Length 524;
Best Local Similarity 100.0%;
Matches 518; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 IWELKKDVYVVELDWYPDAPGEMVVLTCDTPEEDGITWTLDQSSEVLGSGKTLTIQVKEF 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 IWELKKDVYVVELDWYPDAPGEMVVLTCDTPEEDGITWTLDQSSEVLGSGKTLTIQVKEF 60
Qy 61 GDAGQYTCHKGGEVLSHSLLLLHKKEDGIWSTDILKDQKEPKNKTFLRCEAKNYSGRFTC 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 GDAGQYTCHKGGEVLSHSLLLLHKKEDGIWSTDILKDQKEPKNKTFLRCEAKNYSGRFTC 120
Qy 121 WWLTTISTDLTFSVKSSRGSSDPQGVTCGAATLSAERVRGDNKEYEYSVECQEDSACPAA 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 WWLTTISTDLTFSVKSSRGSSDPQGVTCGAATLSAERVRGDNKEYEYSVECQEDSACPAA 180
Qy 181 EESLPIEVMVDAVHKLKYENYTSSFFIRDIIKPDPPKNLQLKPLKNSRQVEVSWEYPDTW 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 EESLPIEVMVDAVHKLKYENYTSSFFIRDIIKPDPPKNLQLKPLKNSRQVEVSWEYPDTW 240
Qy 241 STPHSYFSLTFCVQVQGKSKREKKDRVFTDKTSATVICRKNASISVRAQDRYYSSSWSEW 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 STPHSYFSLTFCVQVQGKSKREKKDRVFTDKTSATVICRKNASISVRAQDRYYSSSWSEW 300
Qy 301 ASVPCSGGGGSGGGGSGGGGSRNLPVATPDPGMFPCLHHSQNLLRAVSNMLQKARQTLEF 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 ASVPCSGGGGSGGGGSGGGGSRNLPVATPDPGMFPCLHHSQNLLRAVSNMLQKARQTLEF 360
Qy 361 YPCTSEEIDHEDITKDKTSTVEACLPLELTKNESCLNSRETSFITNGSCLASRKTSFMMA 420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 361 YPCTSEEIDHEDITKDKTSTVEACLPLELTKNESCLNSRETSFITNGSCLASRKTSFMMA 420
Qy 421 LCLSSIYEDLKMYQVEFKTMNAKLLMDPKRQIFLDQNMLAVIDELMQALNFNSETVPQKS 480
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 421 LCLSSIYEDLKMYQVEFKTMNAKLLMDPKRQIFLDQNMLAVIDELMQALNFNSETVPQKS 480
Qy 481 SLEEPDFYKTKIKLCILLHAFRIRAVTIDRVMSYLNAS 518
||||||||||||||||||||||||||||||||||||||
Db 481 SLEEPDFYKTKIKLCILLHAFRIRAVTIDRVMSYLNAS 518
Lieschke, Jia, and Champion are considered to be analogous to the claim invention because they are in the same field of treating cancer through by leveraging interleukin. Therefore, it would have been prima facie obvious before the effective filing date of the claimed invention to utilize the art-recognized method to include the proven effective IL-12.p40L▲p35 as taught by Lieschke, with the method as taught by Jia and Champion, because doing so would advantageously increase antitumor activity, thereby increasing probability of affecting cancerous cells. One of ordinary skill in the art would have reasonable expectation of success in using the fusion protein to increase efficacy of cancer treatment given that this method is well known, has been successfully demonstrated, and commonly used in the prior art.
Accordingly, the claimed invention was prima facie obvious to one of ordinary skill in the art at the time of filing especially in the absence of evidence to the contrary.
Conclusion
NO CLAIMS ARE ALLOWED.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Danyal H Alam whose telephone number is (571)272-1102. The examiner can normally be reached M - F 9am - 5pm.
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/DANYAL HASSAN ALAM/Examiner, Art Unit 1672
/THOMAS J. VISONE/Supervisory Patent Examiner, Art Unit 1672