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 .
1. Claims 16, 18, and 22 have been cancelled. Claim 23 has been amended.
Claims 1-15, 17, 19-21, and 23 are pending and under examination.
Claim Objections
2. Claim 2 is objected to because of the recitation “is included in a coding region of Hexon of the adenovirus”. Correction to “is inserted into the gene encoding the adenoviral hexon” is required.
3. Claim 3 is objected to because of the recitation “located between codons of a 154th amino acid (gaa, Glu)” and a 155th amino acid (gca, Asp) of the Hexon protein encoded by a base sequence represented by SEQ ID NO: 3”.
Correction to “located between the codons encoding Glu154 and Asp155 of the hexon protein encoded by the nucleic acid sequence set forth by SEQ ID NO: 3” is required.
4. Claim 4 is objected to because of the recitation “is included in a coding region of pIX (protein IX) of the adenovirus”. Correction to “is inserted into the coding sequence of the adenoviral protein IX (pIX)” is required.
5. Claim 5 is objected to because of the recitation “the nucleic acid encoding the albumin binding domain comprises a base sequence represented by SEQ ID NO: 1”. Correction to “the sequence of the nucleic acid encoding the albumin binding domain is set forth by SEQ ID NO: 1” is required.
6. Claim 6 is objected to because of the recitation “wherein the albumin binding domain comprises an amino acid sequence represented by SEQ ID NO: 2”. Correction to “wherein the amino acid sequence of the albumin binding domain is set forth by SEQ ID NO: 2” is required.
7. Claims 7 and 8 are objected to because of the recitation “telomere promoter”. Correction to “telomerase promoter” is required.
8. Claim 9 is objected to because of the recitation “the endogenous gene of the adenovirus has a structure”. Correction to “the adenoviral genome has the structure” is required.
9. Claim 10 is objected to because of the recitation “operably linked to the E1A and E1B of the endogenous genes of the adenovirus”. Correction to “operably linked to E1A and E1B” is required.
10. Claim 12 is objected to because of the recitation “an expression cassette expressing a foreign gene”. Correction to “an expression cassette encoding a heterologous gene” is required.
11. Claim 13 is objected to because of the recitation “included in an E3 region of an endogenous gene of the adenovirus”. Correction to “inserted into the E3 gene of the adenoviral genome” is required.
12. Claim 21 should recite “wherein the composition is formulated for intravenous administration.
13. Claim 23 is objected to because of the recitations “according to claim 1“ and “a subject”. Correction to “of claim 1“ and “to a subject” is required.
Double Patenting
14. 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 U SPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re V ogel, 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.
15. Claims 1-3, 7-15, 17, 19-21, and 23 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3, 6-8, 10, 12-14, 17, 18, 20, 28, 31, and 34 of copending Application No. 18/723,312 (reference application), in view of both Yost-Daljev et al. (Infections and Immunity, 2004, 72: 1775-1785) and Alemany Bonastre et al. (WO 15/166082). Although the claims at issue are not identical, they are not patentably distinct from each other because both claim sets are drawn to the same (1) adenovirus which could be serotype 5 (Ad5), where the adenovirus comprises a binding domain inserted at the same positions into the HVR1 of the adenoviral hexon; and (2) methods for treating cancer by using the adenovirus. Although not recited in the application claims, as evidenced by the attached Sequence Alignment, the Ad5 hexon protein is encoded by SEQ ID NO: 3. The instant specification discloses that the adenovirus could be a chimeric adenovirus having serotype 5/3 (see Fig. 1).
The only difference is that the application claims recite the binding domain is the transferrin binding domain (TBD), not an albumin binding domain (ABD) as required by the instant claims. However, Yost-Daljev et al. teach that the transferrin binding domains provide immune evasion (see paragraph bridging p. 1782 and 1783; paragraph bridging p. 1783 and 1784). One of skill in the art would have readily understood that the TBD recited in the application claims provides the adenovirus with the ability of avoiding the immune responses elicited upon administration into hosts. Furthermore, Alemany Bonastre et al. teach that inserting an ABD into the HVR1 of the adenoviral hexon results in adenoviruses capable of immune evasion (see Abstract; paragraph bridging p. 1 and 2; p. 7, first paragraph). Based on these teachings, one of skill in the art would have found obvious to modify the application claims by replacing TBD with an ABD, to achieve the predictable result of imparting immune evasion to the adenovirus.
Thus, the instant claims and the application claims are obvious variants,
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
16. Claims 1-4, 7-15, 17, 19-21, and 23 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3, 6-8, 10, 12-14, 17, 18, 20, 28, 31, and 34 of copending Application No. 18/723,312 (reference application), in view of both Yost-Daljev et al. and Alemany Bonastre et al., in further view of Kovesdi et al. (WO 17/050128).
The rejection of claims 1-3, 7-15, 17, 19-21, and 23 is addressed above
With respect to the instant claim 4, Kovesdi et al. teach that shielding domains could be incorporated into pIX (see Abstract). Further modifying the application claims by inserting the ABD into pIX would have been obvious to one of skill in the art, to achieve result of obtaining an adenovirus capable of evading the immune responses.
Thus, the instant claims and the application claims are obvious variants,
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
17. Claims 1-3, 6-15, 17, 19-21, and 23 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3, 6-8, 10, 12-14, 17, 18, 20, 28, 31, and 34 of copending Application No. 18/723,312 (reference application), in view of both Yost-Daljev et al. and Alemany Bonastre et al., in further view of Baumhoff et al. (WO 17/081082).
The rejection of claims 1-3, 6-15, 17, 19-21, and 23 is addressed above
With respect to the instant claim 6, the ABD set forth by SEQ ID NO: 2 was taught by Baumhoff et al. (see claim 9 and the attached Sequence Alignment). Using the ABD set forth by SEQ ID NO: 2 as the ABD in the application claims would have been obvious to one of skill in the art, to achieve result of obtaining an adenovirus capable of evading the immune responses.
Thus, the instant claims and the application claims are obvious variants,
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
18. Claims 1-3, 5, 7-15, 17, 19-21, and 23 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3, 7, 8, 10, 12-14, 17, 18, 20, 28, 31, and 34 of copending Application No. 18/723,312 (reference application), in view of both Yost-Daljev et al. and Alemany Bonastre et al., in further view of GenBank LN680995.
The rejection of claims 1-3, 6-15, 17, 19-21, and 23 is addressed above
The application claims do not do not recite the ABD set forth by SEQ ID NO: 1, as recited in the instant claim 5. However, Alemany Bonastre et al. teach that different naturally-occurring and synthetic ABDs could be used to provide immune evasion (see p. 13, lines 19-29; p. 14, lines 1-9; p. 36, line 26 through p. 37, line 2). Thus, one of skill in the art would have looked for other ABDs disclosed by the prior art and GenBank. Using prior art means accomplishing the same goal would have been reasonably obvious to one of skill in the art. As held In re Peterson, 315 F.3d 1325, 1329-30, there is “a normal desire of scientists or artisans to improve upon what is already generally known”. Since the ABD set forth by SEQ ID NO: 1 was disclosed by GenBank LN680995, using this ABD in the application claims would have been obvious to one of skill in the art, to achieve result of obtaining an adenovirus capable of evading the immune responses.
Thus, the instant claims and the application claims are obvious variants,
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claim Rejections - 35 USC § 112(b)
19. 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.
20. Claim 20 is 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 20 is indefinite because it recites both a composition and a method step (specifically, ”is administered”). The recitation “is administered” is not directed to the composition; it is rather directed to the action taken by the person administering the composition. Thus, it is not clear whether the claim is drawn to a composition or to a method of administering the composition.
MPEP 2173.05(p) II states:
A single claim which claims both an apparatus and the method steps of using the apparatus is indefinite under 35 U.S.C. 112(b) or pre-AIA 35 U.S.C. 112, second paragraph. See In re Katz Interactive Call Processing Patent Litigation, 639 F.3d 1303, 97 USPQ2d 1737 (Fed. Cir. 2011). In Katz, a claim directed to "[a] system with an interface means for providing automated voice messages…to certain of said individual callers, wherein said certain of said individual callers digitally enter data" was determined to be indefinite because the italicized claim limitation is not directed to the system, but rather to actions of the individual callers, which creates confusion as to when direct infringement occurs. Katz, 639 F.3d at 1318 (citing IPXL Holdings v. Amazon.com, Inc., 430 F.3d 1377, 1384, 77 USPQ2d 1140, 1145 (Fed. Cir. 2005), in which a system claim that recited "an input means" and required a user to use the input means was found to be indefinite because it was unclear "whether infringement … occurs when one creates a system that allows the user [to use the input means], or whether infringement occurs when the user actually uses the input means."); Ex parte Lyell, 17 USPQ2d 1548 (Bd. Pat. App. & Inter. 1990) (claim directed to an automatic transmission workstand and the method of using it held ambiguous and properly rejected under 35 U.S.C. 112, second paragraph).
Amending claim 20 to replace the recitation “is administered systemically” with “is formulated for systemic administration” would obviate this rejection.
Claim Rejections - 35 USC § 102
21. 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.
22. Claims 1, 2, 7, 8, 12, 14, 15, 17, 19-21, and 23 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Bonastre et al. (WO 15/166082).
Alemany Bonastre et al. teach an oncolytic subgroup C adenovirus, serotype 5 (Ad5), for gene therapy; the oncolytic Ad5 has an albumin binding domain (ABD) inserted into the hexon protein (disclosed by GenBank BAG48782.1); the insertion site is after amino acid D150 of the hypervariable region 1 (HVR1) (claim 1, 2, 14, 15, and 17). The oncolytic Ad5 comprises the hTERT promoter operably linked to an adenoviral gene and a heterologous gene encoding a therapeutic protein to be expressed in the infected cells; it is formulated as a pharmaceutical composition for i.v. administration and it is further administered to subjects in need of cancer therapy (claims 7, 8, 12, 19-21, and 23). The oncolytic Ad5 is capable of acquiring an albumin shield, which provides immune evasion and increased blood persistence after systemic administration (see Abstract; p. 1, first paragraph; p. 7, lines 3-14; p. 9, lines 3-4; p. 10, lines 3-4; paragraph bridging p. 16 and 17; paragraph bridging p. 21 and 22; p. 31, lines 6-26; p. 32, last paragraph; p. 35, lines 16-31; p. 36, lines 1-5 and 13-32; p. 37, lines 1-2, 6-12, and 25-31; p. 38, line 24 through p. 39, line 6). While Alemany Bonastre et al. do not specifically disclose an expression cassette (claim 12), in order to be expressed and provide therapy, the therapeutic gene of Alemany Bonastre et al. must necessarily be operably linked to a promoter (i.e., in an expression cassette). Thus, Alemany Bonastre et al. teach all claim limitations and anticipate the claimed invention.
Claim Rejections - 35 USC § 103
23. 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.
24. Claims 1-3, 6-8, 12, 14, 15, 17, 19-21, and 23 are rejected under 35 U.S.C. 103 as being unpatentable over Alemany Bonastre et al., in view of both Baumhof et al. (WO 17/081082) and GenBank LN680995.
The teachings of Alemany Bonastre et al. are applied as above for claims 1, 2, 7, 8, 12, 14, 15, 17, 19-21, and 23.
With respect to claim 3, Alemany Bonastre et al. teach inserting after D150, not Glu154 (E154). As per MPEP § 716.02, [a]ny differences between the claimed invention and the prior art may be expected to result in some differences in properties. The issue is whether the properties differ to such an extent that the difference is really unexpected. In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
In this case, positions D150 and E154 are very close and both within HVR1. There is no evidence of record that inserting after E154 offers unexpected results over inserting after D150. Inserting after E154 is not patentably relevant if it does not provide a novel feature over inserting after D150.
With respect to the hexon being set forth by SEQ ID NO: 3 (claim 3), Alemany Bonastre et al. teach inserting into Ad5 hexon disclosed by GenBank accession number BAG48782.1 (see the anticipation rejection above). GenBank AB3300086.1 (attached) discloses the nucleic acid sequence encoding BAG48782.1. As evidenced by the attached sequence alignment, the nucleic acid disclosed by AB3300086.1 is identical to SEQ ID NO: 3.
Alemany Bonastre et al. do not teach the ABDs set forth by SEQ ID NOs: 1 and 2 (claims 5 and 6). However, Alemany Bonastre et al. teach that different naturally-occurring and synthetic ABDs could be used to provide immune evasion (see p. 13, lines 19-29; p. 14, lines 1-9; p. 36, line 26 through p. 37, line 2). Thus, one of skill in the art would have looked for other ABDs disclosed by the prior art and GenBank. Using prior art means accomplishing the same goal would have been reasonably obvious to one of skill in the art. Furthermore, Baumhof et al. teach the ABD set forth by SEQ ID NO: 2 (claim 6) (see claim 9 and the attached Sequence Alignment); SEQ ID NO: 1 was disclosed in GenBank (claim 5) (see the attached GenBank Accession LN680995). One of skill in the art would have found obvious to modify Alemany Bonastre et al. by using the ABD set forth by either SEQ ID NO: 1 or SEQ ID NO: 2, to achieve the predictable result of obtaining an oncolytic Ad5 capable of avoiding the immune responses upon administration to subjects. As held In re Peterson, 315 F.3d 1325, 1329-30, there is “a normal desire of scientists or artisans to improve upon what is already generally known”.
Thus, the claimed invention was prima facie obvious at the time of its effective filing date.
25. Claims 1, 2, 4, 7, 8, 12, 14, 15, 17, 19-21, and 23 are rejected under 35 U.S.C. 103 as being unpatentable over Alemany Bonastre et al., in view of Kovesdi et al. (WO 07/050128).
The teachings of Alemany Bonastre et al. are applied as above for claims 1, 2, 7, 8, 12, 14, 15, 17, 19-21, and 23. Alemany Bonastre et al. do not teach inserting into pIX (claim 4). Kovesdi et al. teach that domains providing immune evasion could be inserted into the adenoviral pIX (see Abstract; p. 2, second paragraph, last three lines). One of skill in the art would have found obvious to modify Alemany Bonastre et al. by inserting the ABD into the Ad5 pIX to achieve the predictable result of obtaining an Ad5 capable of evading the immune response upon administration in vivo.
Thus, the claimed invention was prima facie obvious at the time of its effective filing date.
26. Claims 1, 2, 7, 8, 12-15, 17, 19-21, and 23 are rejected under 35 U.S.C. 103 as being unpatentable over Alemany Bonastre et al., in view of Hermiston et al. (WO 01/02540).
The teachings of Alemany Bonastre et al. are applied as above for claims 1, 2, 7, 8, 12, 14, 15, 17, 19-21, and 23. Alemany Bonastre et al. do not specifically teach that the gene encoding the therapeutic protein is inserted in the E3 locus (claim 13). Hermiston et al. teach inserting into the E3 locus, as E3 region encodes several immunoregulatory proteins which are not required for viral replication (see p. 2, line 25 through p. 3, line 3; p. 3, lines 13-17; p. 4, lines 5-11). One of skill in the art would have found obvious to insert the gene encoding the therapeutic protein into the E3 locus, to achieve the predictable result of obtaining an oncolytic Ad5 suitable for cancer therapy.
Thus, the claimed invention was prima facie obvious at the time of its effective filing date.
27. Claims 1, 2, 7-12, 14, 15, 17, 19-21, and 23 are rejected under 35 U.S.C. 103 as being unpatentable over Alemany Bonastre et al., in view of both Fujiwara et al. (PGPUB 2006/0067890) and Champion et al. (WO 15/059303).
The teachings of Alemany Bonastre et al. are applied as above for claims 1, 2, 7, 8, 12, 14, 15, 17, 19-21, and 23. Alemany Bonastre et al. do not specifically teach the limitations of claims 9-11. Fujiwara et al. teach operably linking the hTERT promoter to E1A and further operably linking E1B via an IRES to obtain a replication cassette providing the adenovirus with higher replication ability in the infected cells (see Abstract; [0012]; [0038]-[0040]; Fig. 1). Champion et al. teach a group B oncolytic adenovirus suitable for treating cancer; the adenoviral genome has the configuration 5' ITR-B1-BA-B2-BX-BB-BY-B3-3' ITR, where configuration provides enhanced therapeutic index
Champion et al. teach that B1 comprises E1A-E1B; BA comprises E2B-L1-L2-L3-E2A-L4; B2 includes or does not include E3; BX is a bond or a restriction site and/or a transgene; BB comprises L5; BY is a bond or a restriction site and/or a transgene; B3 is a bond or comprises E4 (see Abstract; p. 2, lines 19-22; p. 3, lines 1-14; p. 9, lines 30-31; p. 10, lines 26-31; p. 29, lines 26-27). Champion et al. teach that the configuration can be applied to any subgroup A-F, including Ad5 (see p. 8). Based on these teachings, one of skill in the art would have found obvious to apply the configuration to the subgroup C Ad5 of Alemany Bonastre et al. and further use hTERT promoter-E1A-IRES-E1B cassette as the E1a-E1B (B1 in Champion et al.) to achieve the predictable result of obtaining Ad5 with enhanced oncolytic activity.
By doing so, one of skill in the art would have obtained the configuration
5' ITR-C1-CA-C2-CX-CC-CY-C3-3' ITR (claim 9), wherein C1 comprises the hTERT promoter-E1A-IRES-E1B cassette (claims 10 and 11).
Thus, the claimed invention was prima facie obvious at the time of its effective filing date.
28. No claim is allowed. No claim is free of prior art.
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/ILEANA POPA/Primary Examiner, Art Unit 1633