DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
Claim Status
The amendments and arguments filed 12/23/25 is acknowledged. Claims 1-16, 18-19, 22, 24-25 are cancelled. New claims 32-33 are added. Claims 17, 20-21, 23, and 26-33 are pending.
Claims 17, 20-21, 23, and 26-33 are currently under consideration for patentability under 37 CFR 1.104.
Information Disclosure Statement
The information disclosure statement filed on 12/23/25 has been considered. A signed copy is enclosed.
New Objections
Claim Objections
Claim 17 is objected to because of the following informalities: the term “L52” and “N72” are named twice. Appropriate correction is required.
Claim Rejections Withdrawn
The rejection of claims 17, 20-21, 23, and 26-31 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement is withdrawn in light of Applicant’s amendments to recite specific mutation sites in the conjugate. The rejection of claim 24 is rendered moot by cancellation of the claim.
The rejection of claims 17, 20-21, 23, and 26-31 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the subject matter which the inventor or a joint inventor, or for pre-AIA the applicant regards as the invention is withdrawn in light of Applicant’s amendments to recite specific mutation sites in the conjugate. The rejection of claim 24 is rendered moot by cancellation of the claim.
The rejection of claim(s) 17, 20-21, 23, 27, and 29-31 under pre-AIA 35 U.S.C. 102(b) as being anticipated by Pavlakis et al (WO 2009/002562 A2; filed 6/27/08; published 12/31/08) is withdrawn in light of Applicant’s amendments to recite specific mutation sites in the conjugate. The rejection of claim 24 is rendered moot by cancellation of the claim.
The rejection of claim(s) 17, 20-21, 23, and 27-31 under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Pavlakis et al (WO 2009/002562 A2; filed 6/27/08; published 12/31/08) in view of Mortier et al (J Biol Chem. 2006 Jan 20;281(3):1612-9. Epub 2005 Nov 11) is withdrawn in light of Applicant’s amendments to recite specific mutation sites in the conjugate. The rejection of claim 24 is rendered moot by cancellation of the claim.
The rejection of claim(s) 17, 20-21, 23, and 27-31 under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Pavlakis et al (WO 2009/002562 A2; filed 6/27/08; published 12/31/08) in view of Jacques et al. (US 2009/0238791, filed 10/6/06, published 9/24/2009) is withdrawn in light of Applicant’s amendments to recite specific mutation sites in the conjugate. The rejection of claim 24 is rendered moot by cancellation of the claim.
The rejection of claim(s) 17, 20-21, 23, and 26-31 under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Pavlakis et al (WO 2009/002562 A2; filed 6/27/08; published 12/31/08) in view of Kaspar et al (Cancer Res 2007; 67: (10)) is withdrawn in light of Applicant’s amendments to recite specific mutation sites in the conjugate. The rejection of claim 24 is rendered moot by cancellation of the claim.
Claim Rejections Maintained
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 §§ 706.02(l)(1) - 706.02(l)(3) 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 USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The 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/process/file/efs/guidance/eTD-info-I.jsp.
The rejection of claims 17, 20-21, 23, 26, and 28-33 on the ground of nonstatutory double patenting as being unpatentable over claims 1-7 of U.S. Patent No. 11,273,204 in view of Kaspar et al (Cancer Res 2007; 67: (10)) is maintained. The rejection of claim 24 is rendered moot by cancellation of the claims.
Although the claims at issue are not identical, they are not patentably distinct from each other.
The instant claims are drawn to an immunocytokine comprising a conjugate comprising a polypeptide comprising the amino acid sequence of IL-15 or a derivative thereof having at least 92.5% sequence identity to SEQ ID NO:3, and a polypeptide comprising the amino acid sequence of IL-15Ralpha having at the amino acid sequence of SEQ ID NO:8 or 9, wherein the il-15 and IL-15Ralpha are separated by a linker sequence. The immunocytokine also comprises an antibody directly linked by covalence or through a linker to the conjugate. The immunocytokine can comprise a conjugate that is a fusion protein. The IL-15 and IL-15Ralpha may or may not be separated by a linker sequence. The sushi domain can have the sequence of SEQ ID NO:8, 9, or 12. The IL-15 can be C-terminal to the sushi domain. The antigen bound by the antibody can be those listed in instant claims 26 and 27. The conjugate can be C-terminal to the antibody. The immunocytokine can be in a pharmaceutical composition with a pharmaceutically acceptable carrier. The claims further comprise a method of treating cancer comprising administering the immunocytokine, wherein the pharmaceutical composition is administered at a dose of 2.5 mg/kg or less.
The reference patent teaches an immunocytokine comprising a) a conjugate comprising an IL-15 of SEQ ID NO:3 or a variant comprising at least one amino acid substitution from those in reference claim 1 (see e.g. claim 1), and a polypeptide comprising the sushi domain of an IL-15Ra of SEQ ID NO:12 (see e.g. claim 1), wherein the conjugate is linked covalently to an antibody; and a pharmaceutical composition thereof (see claims 1-7). SEQ ID NO:3 and 12 of the reference patent are identical to instant SEQ ID NO:3 and 12, respectively.
The reference patent does not teach that the antibody must be directed to a tumor antigen or tumor neovascularization antigen. The reference patent does not teach the linkage of the conjugate with the antibody wherein the antibody is linked via a linker sequence, wherein the antibody is directed to an antigen such as EDB domain of fibronectin, or wherein the conjugate is C-terminal to the antibody.
Kaspar et al teach a targeted immunocytokine comprising L19 scFV and IL-15 (see abstract). L19 is a high-affinity human antibody specific to EDB, which has been well established both in animal models of cancer and in patients with solid tumors (see e.g. page 4940, right column). Kaspar et al teach fusion of IL-15 at the COOH terminus or at the NH2 terminus of the scFv(L19) in diabody format with the GSSGG linker, yielding the immunocytokines L19-IL-15 (Fig. 1C) and IL-15-L19 (Fig. 1D) (see e.g. page 4943).
It would have been prima facie obvious to one of ordinary skill in the art at the time of the invention to place the conjugate at the C-terminus of the antibody molecule, with a linker, to promote the activity of the IL-15 in the reference patent. Kaspar et al teach that only the C-terminal fusions of scFV and Il-15 (scFv(L19)-IL-15) displayed activity levels comparable to recombinant human IL-15 when tested, whereas the N-terminal fusion (IL-15-scFV(L19)) showed no biological activity at all (see page 4943). Additionally, Kaspar et al showed that the length and composition of the linker can affect the ability of the antibody to form noncovalent homodimers. Therefore, the linkers can ensure that the proteins form proper secondary and tertiary structures within the immunocytokine conjugate. The advantage of maintaining biological activity through the choice of linking the conjugate to the C-terminus of the antibody, combined with the advantage of being able to manipulate the antibody dimer formation, thereby linking the two components of the conjugate with an antibody in a manner that that allows for proper protein structure that is required for binding of both the antibody and the conjugate, provides the motivation to make the aforementioned modification of the conjugate of the reference patent, based on the teachings of Kaspar et al, with a reasonable expectation of success.
Additionally, KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007), discloses that if a technique has been used to improve one method, and a person of ordinary skill would recognize that it would be used in similar methods in the same way, using the technique is obvious unless its application is beyond that person’s skill. It would be obvious to apply a known technique to a known product to be used in a known method that is ready for improvement to yield predictable results. Thus, the combination of prior art references as combined provided a prima facie case of obviousness, absent convincing evidence to the contrary.
The rejection of claims 17, 20-21, 23, and 27-33 on the ground of nonstatutory double patenting as being unpatentable over claims 1-7 of U.S. Patent No. 11,273,204 in view of Pavlakis et al (WO 2009/002562 A2; filed 6/27/08; published 12/31/08) is maintained. The rejection of claim 24 is rendered moot by cancellation of the claims.
Although the claims at issue are not identical, they are not patentably distinct from each other.
The instant claims are drawn to an immunocytokine comprising a conjugate comprising a polypeptide comprising the amino acid sequence of IL-15 or a derivative thereof having at least 92.5% sequence identity to SEQ ID NO:3, and a polypeptide comprising the amino acid sequence of IL-15Ralpha having at the amino acid sequence of SEQ ID NO:8 or 9, wherein the il-15 and IL-15Ralpha are separated by a linker sequence. The immunocytokine also comprises an antibody directly linked by covalence or through a linker to the conjugate. The immunocytokine can comprise a conjugate that is a fusion protein. The IL-15 and IL-15Ralpha may or may not be separated by a linker sequence. The sushi domain can have the sequence of SEQ ID NO:8, 9, or 12. The IL-15 can be C-terminal to the sushi domain. The antigen bound by the antibody can be those listed in instant claims 26 and 27. The conjugate can be C-terminal to the antibody. The immunocytokine can be in a pharmaceutical composition with a pharmaceutically acceptable carrier. The claims further comprise a method of treating cancer comprising administering the immunocytokine, wherein the pharmaceutical composition is administered at a dose of 2.5 mg/kg or less.
The reference patent teaches an immunocytokine comprising a) a conjugate comprising an IL-15 of SEQ ID NO:3 or a variant comprising at least one amino acid substitution from those in reference claim 1 (see e.g. claim 1), and a polypeptide comprising the sushi domain of an IL-15Ra of SEQ ID NO:12 (see e.g. claim 1), wherein the conjugate is linked covalently to an antibody; and a pharmaceutical composition thereof (see claims 1-7). SEQ ID NO:3 and 12 of the reference patent are identical to instant SEQ ID NO:3 and 12, respectively.
The reference patent does not teach that the antibody must be directed to a tumor antigen or tumor neovascularization antigen, such as CEA or HER2.
Pavlakis teaches complexes that comprise IL-15 covalently or noncovalently bound to interleukin-15 receptor alpha ("IL-15Ra") ("IL-15/IL-15Ra complexes") (see e.g. paragraph [0011] and claim 10-13). The IL-15/IL-15Ra complex may comprise native IL-15 or an IL-15 derivative covalently or noncovalently bound to native IL15Ra or an IL-15Ra derivative, with the term “bound” indicating that no linker is present between the peptides (see e.g. paragraph [0011]). The complexes may also comprise a heterologous molecule, such as an antibody that specifically binds to an antigen associated with disease to be treated (see e.g. paragraph [0012] and [0084]-[0085], and claim 15). Non-limiting example antigens include tumor antigens (see e.g. paragraph [0012] and [0084]-[0085]). The heterologous molecule can be conjugated to IL-15 or IL-15Ra, indicating covalent linkage. The IL-15 can comprise SEQ ID NO:1 (see e.g. paragraph [0026]; the sequence of instant SEQ ID NO:3 is underlined):
MRISKPHLRSISIQCYLCLLLNSHFLTEAGIHVFILGCFSAGLPKTEANWVNVISDLKKIEDLIQSMHIDATLYTESDVHPSCKVTAMKCFLLELOVISLESGDASIHDTVENLIILANNSLSSNGNVTESGCKECEELEEKNIKEFLQSFVHIVOMFINTS (SEQ ID NO: 1).
The IL-15Ralpha can comprise SEQ ID NO:3 (see e.g. paragraph [0035]; the sequence of instant SEQ ID NO:8 is underlined; the sequence of instant SEQ ID NO:12 is in bold):
MAPRRARGCRTLGLPALLLLLLLRPPATRGITCPPPMSVEHADIWVKSYSLYSRERYICNSGFKRKAGTSSLTECVLNKATNVAHWTTPSLKCIRDPALVHQRPAPPSTVTTAGVTPQPESLSPSGKEPAASSPSSNNTAATTAAIVPGSQLMPSKSPSTGTTEISSHESSHGTPSQTTAKNWELTASASHQPPGVYPQGHSDTTVAISTSTVLLCGLSAVSLLACYLKSROTPPLASVEMEAMEALPVTWGTSSRDEDLENCSHHL (SEQ ID NO: 3).
Pavlakis teaches that the antigen can comprise CEA, EGFR, HER2, or others (see e.g. paragraph [0084]-[0085]). The complex can be present in a pharmaceutical composition comprising a pharmaceutically acceptable carrier (see e.g. [00149]).
It would have been obvious to one with ordinary skill in the art, at the time of the invention, that the fusion protein could lack a linker between antibody and conjugate, and that the antibody could be an antibody directed to a tumor antigen such as CEA or HER2 because the Supreme Court set forth in KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007), that if the scope and content of the prior art included a similar or analogous product, with differences between the claimed invention and prior art that were encompassed in known variation or in a principle known in the art, and one of ordinary skill in the art could have combined the elements as claimed by known methods, the claimed variation would have been predictable in to one of ordinary skill in the art. Pavlakis provides a complex of IL-15/IL-15Ralpha sushi domain using the same amino acid sequences as the reference patent, and Pavlakis indicates that the combination of the complex is with antibodies that bind to CEA or HER2, among other antigens, is known in the art. Therefore, the differences between the reference patent and Pavlakis were encompassed in known variation or in a principle known in the art. Thus, the combination of prior art references as combined provided a prima facie case of obviousness, absent convincing evidence to the contrary.
Additionally, KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007), discloses that if a technique has been used to improve one method, and a person of ordinary skill would recognize that it would be used in similar methods in the same way, using the technique is obvious unless its application is beyond that person’s skill. It would be obvious to apply a known technique to a known product to be used in a known method that is ready for improvement to yield predictable results. Thus, the combination of prior art references as combined provided a prima facie case of obviousness, absent convincing evidence to the contrary.
The provisional rejection of claims 17, 20-21, 23, and 28-33 on the ground of nonstatutory double patenting as being unpatentable over claims 1-3, 6-19, and 23-25 of copending Application No. 17/693,132 (reference application) is maintained. The rejection of claim 24 is rendered moot by cancellation of the claims.
Although the claims at issue are not identical, they are not patentably distinct from each other.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
The instant claims are drawn to an immunocytokine comprising a conjugate comprising a polypeptide comprising the amino acid sequence of IL-15 or a derivative thereof having at least 92.5% sequence identity to SEQ ID NO:3, and a polypeptide comprising the amino acid sequence of IL-15Ralpha having at the amino acid sequence of SEQ ID NO:8 or 9, wherein the il-15 and IL-15Ralpha are separated by a linker sequence. The immunocytokine also comprises an antibody directly linked by covalence or through a linker to the conjugate. The immunocytokine can comprise a conjugate that is a fusion protein. The IL-15 and IL-15Ralpha may or may not be separated by a linker sequence. The sushi domain can have the sequence of SEQ ID NO:8, 9, or 12. The IL-15 can be C-terminal to the sushi domain. The antigen bound by the antibody can be those listed in instant claims 26 and 27. The conjugate can be C-terminal to the antibody. The immunocytokine can be in a pharmaceutical composition with a pharmaceutically acceptable carrier. The claims further comprise a method of treating cancer comprising administering the immunocytokine, wherein the pharmaceutical composition is administered at a dose of 2.5 mg/kg or less.
The reference claims are directed to an immunocytokine comprising a conjugate and an antibody that binds to PD-1, PD-L1, or PD-L1, which are tumor antigens (see e.g. claim 1). The immunocytokine comprises the amino acid sequence of IL-15 or derivatives thereof having at least 92.5% sequence identity to SEQ ID NO:3, and a polypeptide comprising the amino acid sequence of IL-15alpha or derivatives thereof having at least 92% sequence identity to SEQ ID NO:8, wherein SEQ ID NO:3 and 8 are identical to instant SEQ ID NO:3 and 8, respectively, and also comprising an antibody linked by covalence to the conjugate (see e.g. claim 1). The immunocytokine can comprise a conjugate that is a fusion protein (see e.g. claim 10, 19). The immunocytokine may or may not be separated by a linker sequence (see e.g. claim 11, 18, and 19). The IL-15Ralpha domain can comprise an amino acid sequence at least 93% identical to SEQ ID NO:12, which has an identical sequence to instant SEQ ID NO:12 (see e.g. claim 7). The IL-15 can be C-terminal to the IL-15Ralpha domain (see e.g. claim 15). The conjugate can be C-terminal to the antibody (see e.g. claim 17). The immunocytokine can be present in an pharmaceutical composition with a carrier (see e.g. claim 23).
The copending claims differ in scope from the instant claims because the copending claims recite a specific set of antigens for the antibody, and also recite various mutations and levels of sequence identity. The copending claims recite species that fall within the instant claimed genus, therefore while the claims anticipate the instant claims, the scope is different. Further, the copending claims recite a method using the immunocytokine, which is not recited in the examined claims.
The provisional rejection of claims 17, 20-21, 23, and 28-31 on the ground of nonstatutory double patenting as being unpatentable over claims 1, 4, 6-14, 16-17, and 19 of copending Application No. 17/677,589 (reference application) is maintained. The rejection of claim 24 is rendered moot by cancellation of the claims.
Although the claims at issue are not identical, they are not patentably distinct from each other.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
The instant claims are drawn to an immunocytokine comprising a conjugate comprising a polypeptide comprising the amino acid sequence of IL-15 or a derivative thereof having at least 92.5% sequence identity to SEQ ID NO:3, and a polypeptide comprising the amino acid sequence of IL-15Ralpha having at the amino acid sequence of SEQ ID NO:8 or 9, wherein the il-15 and IL-15Ralpha are separated by a linker sequence. The immunocytokine also comprises an antibody directly linked by covalence or through a linker to the conjugate. The immunocytokine can comprise a conjugate that is a fusion protein. The IL-15 and IL-15Ralpha may or may not be separated by a linker sequence. The sushi domain can have the sequence of SEQ ID NO:8, 9, or 12. The IL-15 can be C-terminal to the sushi domain. The antigen bound by the antibody can be those listed in instant claims 26 and 27. The conjugate can be C-terminal to the antibody. The immunocytokine can be in a pharmaceutical composition with a pharmaceutically acceptable carrier. The claims further comprise a method of treating cancer comprising administering the immunocytokine, wherein the pharmaceutical composition is administered at a dose of 2.5 mg/kg or less.
The reference claims are directed to a method for treating cancer with an immunocytokine comprising administering a conjugate and an antibody that binds to PD-1, PD-L1, or PD-L1, which are tumor antigens (see e.g. claim 1). The immunocytokine comprises the amino acid sequence of IL-15 or derivatives thereof having at least 92.5% sequence identity to SEQ ID NO:3, and a polypeptide comprising the amino acid sequence of IL-15alpha or derivatives thereof having at least 93% sequence identity to SEQ ID NO:8, wherein SEQ ID NO:3 and 8 are identical to instant SEQ ID NO:3 and 8, respectively, and also comprising an antibody linked by covalence to the conjugate (see e.g. claim 1). The immunocytokine can comprise a conjugate that is a fusion protein (see e.g. claim 19). The immunocytokine may or may not be separated by a linker sequence (see e.g. claim 7 and 10). The IL-15Ralpha domain can comprise an amino acid sequence at least 93% identical to SEQ ID NO:12, which has an identical sequence to instant SEQ ID NO:12 (see e.g. claim 6). The IL-15 can be C-terminal to the IL-15Ralpha domain (see e.g. claim 12). The conjugate can be C-terminal to the antibody (see e.g. claim 15). The immunocytokine is present in an pharmaceutical composition if capable of being administered to subjects for treatment (see e.g. claim 1-19).
The copending claims differ in scope from the instant claims because the copending claims recite a method, and the immunocytokines are limited to a specific set of antigens for the antibody, and the claims also recite various mutations and levels of sequence identity. The copending claims recite species of immunocytokines that fall within the instant claimed genus, therefore while the claims anticipate the instant claims, the scope is different.
The rejection of claims 17, 20-21, 23, and 28-33 on the ground of nonstatutory double patenting as being unpatentable over claims 1-8 of U.S. Patent No. 10,626,155 is maintained. The rejection of claim 24 is rendered moot by cancellation of the claims.
Although the claims at issue are not identical, they are not patentably distinct from each other.
The instant claims are drawn to an immunocytokine comprising a conjugate comprising a polypeptide comprising the amino acid sequence of IL-15 or a derivative thereof having at least 92.5% sequence identity to SEQ ID NO:3, and a polypeptide comprising the amino acid sequence of IL-15Ralpha having at the amino acid sequence of SEQ ID NO:8 or 9, wherein the il-15 and IL-15Ralpha are separated by a linker sequence. The immunocytokine also comprises an antibody directly linked by covalence or through a linker to the conjugate. The immunocytokine can comprise a conjugate that is a fusion protein. The IL-15 and IL-15Ralpha may or may not be separated by a linker sequence. The sushi domain can have the sequence of SEQ ID NO:8, 9, or 12. The IL-15 can be C-terminal to the sushi domain. The antigen bound by the antibody can be those listed in instant claims 26 and 27. The conjugate can be C-terminal to the antibody. The immunocytokine can be in a pharmaceutical composition with a pharmaceutically acceptable carrier. The claims further comprise a method of treating cancer comprising administering the immunocytokine, wherein the pharmaceutical composition is administered at a dose of 2.5 mg/kg or less.
The reference patent teaches an immunocytokine comprising a) a conjugate comprising an IL-15 and the sushi domain of an IL-15Ra wherein the conjugate is linked directly or indirectly and covalently to an antibody; and a pharmaceutical composition thereof (see claims 1-8). The immunocytokine comprises SEQ ID NO:17 for the IL-15/IL-15Ralpha conjugate, and SEQ ID NO:17 comprises a sequence identical to instant SEQ ID NO:12 (sushi domain) followed by a linker, which is followed by a sequence identical to instant SEQ ID NO:3 (see e.g. claim 1 and SEQ ID NO:17 starting in Column 53). The antibody may not be linked by any linker sequence (see e.g. claim 2), or the conjugate and antibody can be separated by linker sequence (see e.g. claim 3). The antibody can be directed against tumor antigens (se e.g. claim 4 and 6). The conjugate can be C-terminal to the antibody (see e.g. claim 5). The immunocytokine can be produced in a pharmaceutical composition with a carrier (see e.g. claim 7-8).
The reference patent has a narrower scope than the instant claims, because the conjugate is limited to the sequence of SEQ ID NO:17, whereas the instant claims encompass a broader range of conjugates. Therefore the scope of the claims overlaps but is not identical.
The rejection of claims 17, 20-21, 23, 26, and 28-33 on the ground of nonstatutory double patenting as being unpatentable over claims 1-8 of U.S. Patent No. 10,626,155 in view of Kaspar et al (Cancer Res 2007; 67: (10)) is maintained. The rejection of claim 24 is rendered moot by cancellation of the claims.
Although the claims at issue are not identical, they are not patentably distinct from each other.
The instant claims are drawn to an immunocytokine comprising a conjugate comprising a polypeptide comprising the amino acid sequence of IL-15 or a derivative thereof having at least 92.5% sequence identity to SEQ ID NO:3, and a polypeptide comprising the amino acid sequence of IL-15Ralpha having at the amino acid sequence of SEQ ID NO:8 or 9, wherein the il-15 and IL-15Ralpha are separated by a linker sequence. The immunocytokine also comprises an antibody directly linked by covalence or through a linker to the conjugate. The immunocytokine can comprise a conjugate that is a fusion protein. The IL-15 and IL-15Ralpha may or may not be separated by a linker sequence. The sushi domain can have the sequence of SEQ ID NO:8, 9, or 12. The IL-15 can be C-terminal to the sushi domain. The antigen bound by the antibody can be those listed in instant claims 26 and 27. The conjugate can be C-terminal to the antibody. The immunocytokine can be in a pharmaceutical composition with a pharmaceutically acceptable carrier. The claims further comprise a method of treating cancer comprising administering the immunocytokine, wherein the pharmaceutical composition is administered at a dose of 2.5 mg/kg or less.
The reference patent teaches an immunocytokine comprising a) a conjugate comprising an IL-15 and the sushi domain of an IL-15Ra wherein the conjugate is linked directly or indirectly and covalently to an antibody; and a pharmaceutical composition thereof (see claims 1-8). The immunocytokine comprises SEQ ID NO:17 for the IL-15/IL-15Ralpha conjugate, and SEQ ID NO:17 comprises a sequence identical to instant SEQ ID NO:12 (sushi domain) followed by a linker, which is followed by a sequence identical to instant SEQ ID NO:3 (see e.g. claim 1 and SEQ ID NO:17 starting in Column 53). The antibody may not be linked by any linker sequence (see e.g. claim 2), or the conjugate and antibody can be separated by linker sequence (see e.g. claim 3). The antibody can be directed against tumor antigens (se e.g. claim 4 and 6). The conjugate can be C-terminal to the antibody (see e.g. claim 5). The immunocytokine can be produced in a pharmaceutical composition with a carrier (see e.g. claim 7-8).
The reference patent does not teach the linkage of the conjugate with the antibody wherein the antibody is linked via a linker sequence, wherein the antibody is directed to an antigen such as EDB domain of fibronectin, or wherein the conjugate is C-terminal to the antibody.
Kaspar et al teach a targeted immunocytokine comprising L19 scFV and IL-15 (see abstract). L19 is a high-affinity human antibody specific to EDB, which has been well established both in animal models of cancer and in patients with solid tumors (see e.g. page 4940, right column). Kaspar et al teach fusion of IL-15 at the COOH terminus or at the NH2 terminus of the scFv(L19) in diabody format with the GSSGG linker, yielding the immunocytokines L19-IL-15 (Fig. 1C) and IL-15-L19 (Fig. 1D) (see e.g. page 4943).
It would have been prima facie obvious to one of ordinary skill in the art at the time of the invention to place the conjugate at the C-terminus of the antibody molecule, with a linker, to promote the activity of the IL-15 in the reference patent. Kaspar et al teach that only the C-terminal fusions of scFV and Il-15 (scFv(L19)-IL-15) displayed activity levels comparable to recombinant human IL-15 when tested, whereas the N-terminal fusion (IL-15-scFV(L19)) showed no biological activity at all (see page 4943). Additionally, Kaspar et al showed that the length and composition of the linker can affect the ability of the antibody to form noncovalent homodimers. Therefore, the linkers can ensure that the proteins form proper secondary and tertiary structures within the immunocytokine conjugate. The advantage of maintaining biological activity through the choice of linking the conjugate to the C-terminus of the antibody, combined with the advantage of being able to manipulate the antibody dimer formation, thereby linking the two components of the conjugate with an antibody in a manner that that allows for proper protein structure that is required for binding of both the antibody and the conjugate, provides the motivation to make the aforementioned modification of the conjugate of the reference patent, based on the teachings of Kaspar et al, with a reasonable expectation of success.
Additionally, KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007), discloses that if a technique has been used to improve one method, and a person of ordinary skill would recognize that it would be used in similar methods in the same way, using the technique is obvious unless its application is beyond that person’s skill. It would be obvious to apply a known technique to a known product to be used in a known method that is ready for improvement to yield predictable results. Thus, the combination of prior art references as combined provided a prima facie case of obviousness, absent convincing evidence to the contrary.
The rejection of claims 17, 20-21, 23, and 26-33 on the ground of nonstatutory double patenting as being unpatentable over claims 1-8 of U.S. Patent No. 10,626,155 in view of Pavlakis et al (WO 2009/002562 A2; filed 6/27/08; published 12/31/08) is maintained. The rejection of claim 24 is rendered moot by cancellation of the claims.
Although the claims at issue are not identical, they are not patentably distinct from each other.
The instant claims are drawn to an immunocytokine comprising a conjugate comprising a polypeptide comprising the amino acid sequence of IL-15 or a derivative thereof having at least 92.5% sequence identity to SEQ ID NO:3, and a polypeptide comprising the amino acid sequence of IL-15Ralpha having at the amino acid sequence of SEQ ID NO:8 or 9, wherein the il-15 and IL-15Ralpha are separated by a linker sequence. The immunocytokine also comprises an antibody directly linked by covalence or through a linker to the conjugate. The immunocytokine can comprise a conjugate that is a fusion protein. The IL-15 and IL-15Ralpha may or may not be separated by a linker sequence. The sushi domain can have the sequence of SEQ ID NO:8, 9, or 12. The IL-15 can be C-terminal to the sushi domain. The antigen bound by the antibody can be those listed in instant claims 26 and 27. The conjugate can be C-terminal to the antibody. The immunocytokine can be in a pharmaceutical composition with a pharmaceutically acceptable carrier. The claims further comprise a method of treating cancer comprising administering the immunocytokine, wherein the pharmaceutical composition is administered at a dose of 2.5 mg/kg or less.
The reference patent teaches an immunocytokine comprising a) a conjugate comprising an IL-15 and the sushi domain of an IL-15Ra wherein the conjugate is linked directly or indirectly and covalently to an antibody; and a pharmaceutical composition thereof (see claims 1-8). The immunocytokine comprises SEQ ID NO:17 for the IL-15/IL-15Ralpha conjugate, and SEQ ID NO:17 comprises a sequence identical to instant SEQ ID NO:12 (sushi domain) followed by a linker, which is followed by a sequence identical to instant SEQ ID NO:3 (see e.g. claim 1 and SEQ ID NO:17 starting in Column 53). The antibody may not be linked by any linker sequence (see e.g. claim 2), or the conjugate and antibody can be separated by linker sequence (see e.g. claim 3). The antibody can be directed against tumor antigens (se e.g. claim 4 and 6). The conjugate can be C-terminal to the antibody (see e.g. claim 5). The immunocytokine can be produced in a pharmaceutical composition with a carrier (see e.g. claim 7-8).
The reference patent does not teach that the antibody must be directed to a tumor antigen or tumor neovascularization antigen, such as CEA or HER2.
Pavlakis teaches complexes that comprise IL-15 covalently or noncovalently bound to interleukin-15 receptor alpha ("IL-15Ra") ("IL-15/IL-15Ra complexes") (see e.g. paragraph [0011] and claim 10-13). The IL-15/IL-15Ra complex may comprise native IL-15 or an IL-15 derivative covalently or noncovalently bound to native IL15Ra or an IL-15Ra derivative, with the term “bound” indicating that no linker is present between the peptides (see e.g. paragraph [0011]). The complexes may also comprise a heterologous molecule, such as an antibody that specifically binds to an antigen associated with disease to be treated (see e.g. paragraph [0012] and [0084]-[0085], and claim 15). Non-limiting example antigens include tumor antigens (see e.g. paragraph [0012] and [0084]-[0085]). The heterologous molecule can be conjugated to IL-15 or IL-15Ra, indicating covalent linkage. The IL-15 can comprise SEQ ID NO:1 (see e.g. paragraph [0026]; the sequence of instant SEQ ID NO:3 is underlined):
MRISKPHLRSISIQCYLCLLLNSHFLTEAGIHVFILGCFSAGLPKTEANWVNVISDLKKIEDLIQSMHIDATLYTESDVHPSCKVTAMKCFLLELOVISLESGDASIHDTVENLIILANNSLSSNGNVTESGCKECEELEEKNIKEFLQSFVHIVOMFINTS (SEQ ID NO: 1).
The IL-15Ralpha can comprise SEQ ID NO:3 (see e.g. paragraph [0035]; the sequence of instant SEQ ID NO:8 is underlined; the sequence of instant SEQ ID NO:12 is in bold):
MAPRRARGCRTLGLPALLLLLLLRPPATRGITCPPPMSVEHADIWVKSYSLYSRERYICNSGFKRKAGTSSLTECVLNKATNVAHWTTPSLKCIRDPALVHQRPAPPSTVTTAGVTPQPESLSPSGKEPAASSPSSNNTAATTAAIVPGSQLMPSKSPSTGTTEISSHESSHGTPSQTTAKNWELTASASHQPPGVYPQGHSDTTVAISTSTVLLCGLSAVSLLACYLKSROTPPLASVEMEAMEALPVTWGTSSRDEDLENCSHHL (SEQ ID NO: 3).
Pavlakis teaches that the antigen can comprise CEA, EGFR, HER2, or others (see e.g. paragraph [0084]-[0085]). The complex can be present in a pharmaceutical composition comprising a pharmaceutically acceptable carrier (see e.g. [00149]).
It would have been obvious to one with ordinary skill in the art, at the time of the invention, that the antibody could be an antibody directed to a tumor antigen such as CEA or HER2 because the Supreme Court set forth in KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007), that if the scope and content of the prior art included a similar or analogous product, with differences between the claimed invention and prior art that were encompassed in known variation or in a principle known in the art, and one of ordinary skill in the art could have combined the elements as claimed by known methods, the claimed variation would have been predictable in to one of ordinary skill in the art. Pavlakis provides a complex of IL-15/sushi of IL-15Ralpha using the same amino acid sequences as the reference patent, and indicates that the combination of this complex is with antibodies that bind to CEA or HER2, among other antigens, is known in the art. Therefore, the differences between the reference patent and Pavlakis were encompassed in known variation or in a principle known in the art. Thus, the combination of prior art references as combined provided a prima facie case of obviousness, absent convincing evidence to the contrary.
Additionally, KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007), discloses that if a technique has been used to improve one method, and a person of ordinary skill would recognize that it would be used in similar methods in the same way, using the technique is obvious unless its application is beyond that person’s skill. It would be obvious to apply a known technique to a known product to be used in a known method that is ready for improvement to yield predictable results. Thus, the combination of prior art references as combined provided a prima facie case of obviousness, absent convincing evidence to the contrary.
The rejection of claims 17, 20-21, 23, and 26-33 on the ground of nonstatutory double patenting as being unpatentable over claims 1-5 of U.S. Patent No. 10,899,816 in view of Kaspar et al (Cancer Res 2007; 67: (10)) is maintained. The rejection of claim 24 is rendered moot by cancellation of the claims.
Although the claims at issue are not identical, they are not patentably distinct from each other.
The instant claims are drawn to an immunocytokine comprising a conjugate comprising a polypeptide comprising the amino acid sequence of IL-15 or a derivative thereof having at least 92.5% sequence identity to SEQ ID NO:3, and a polypeptide comprising the amino acid sequence of IL-15Ralpha having at the amino acid sequence of SEQ ID NO:8 or 9, wherein the il-15 and IL-15Ralpha are separated by a linker sequence. The immunocytokine also comprises an antibody directly linked by covalence or through a linker to the conjugate. The immunocytokine can comprise a conjugate that is a fusion protein. The IL-15 and IL-15Ralpha may or may not be separated by a linker sequence. The sushi domain can have the sequence of SEQ ID NO:8, 9, or 12. The IL-15 can be C-terminal to the sushi domain. The antigen bound by the antibody can be those listed in instant claims 26 and 27. The conjugate can be C-terminal to the antibody. The immunocytokine can be in a pharmaceutical composition with a pharmaceutically acceptable carrier. The claims further comprise a method of treating cancer comprising administering the immunocytokine, wherein the pharmaceutical composition is administered at a dose of 2.5 mg/kg or less.
The reference patent teaches a conjugate comprising a) a conjugate comprising an IL-15 and the sushi domain of an IL-15Ra wherein the conjugate is linked directly or indirectly and covalently to an antibody; and a pharmaceutical composition thereof (see claims 1-5). The conjugate comprises SEQ ID NO:17 for the IL-15/IL-15Ralpha conjugate, and SEQ ID NO:17 comprises a sequence identical to instant SEQ ID NO:12 (sushi domain) followed by a linker, which is followed by a sequence identical to instant SEQ ID NO:3 (see e.g. claim 1 and SEQ ID NO:17 starting in Column 53). The conjugate can be produced in a pharmaceutical composition with a carrier (see e.g. claim 2-4).
The reference patent does not teach linkage of the conjugate with an antibody, the linkage of the conjugate with the antibody wherein the antibody is linked via a linker sequence, wherein the antibody is directed to an antigen such as EDB domain of fibronectin, or wherein the conjugate is C-terminal to the antibody.
Kaspar et al teach a targeted immunocytokine comprising L19 scFV and IL-15 (see abstract). L19 is a high-affinity human antibody specific to EDB, which has been well established both in animal models of cancer and in patients with solid tumors (see e.g. page 4940, right column). Kaspar et al teach fusion of IL-15 at the COOH terminus or at the NH2 terminus of the scFv(L19) in diabody format with the GSSGG linker, yielding the immunocytokines L19-IL-15 (Fig. 1C) and IL-15-L19 (Fig. 1D) (see e.g. page 4943).
It would have been prima facie obvious to one of ordinary skill in the art at the time of the invention to place the conjugate at the C-terminus of the antibody molecule, with a linker, to promote the activity of the IL-15 in the reference patent. Kaspar et al teach that only the C-terminal fusions of scFV and Il-15 (scFv(L19)-IL-15) displayed activity levels comparable to recombinant human IL-15 when tested, whereas the N-terminal fusion (IL-15-scFV(L19)) showed no biological activity at all (see page 4943). Additionally, Kaspar et al showed that the length and composition of the linker can affect the ability of the antibody to form noncovalent homodimers. Therefore, the linkers can ensure that the proteins form proper secondary and tertiary structures within the immunocytokine conjugate. The advantage of maintaining biological activity through the choice of linking the conjugate to the C-terminus of the antibody, combined with the advantage of being able to manipulate the antibody dimer formation, thereby linking the two components of the conjugate with an antibody in a manner that that allows for proper protein structure that is required for binding of both the antibody and the conjugate, provides the motivation to make the aforementioned modification of the conjugate of the reference patent, based on the teachings of Kaspar et al, with a reasonable expectation of success.
Additionally, KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007), discloses that if a technique has been used to improve one method, and a person of ordinary skill would recognize that it would be used in similar methods in the same way, using the technique is obvious unless its application is beyond that person’s skill. It would be obvious to apply a known technique to a known product to be used in a known method that is ready for improvement to yield predictable results. Thus, the combination of prior art references as combined provided a prima facie case of obviousness, absent convincing evidence to the contrary.
The rejection of claims 17, 20-21, 23, and 26-33 on the ground of nonstatutory double patenting as being unpatentable over claims 1-5 of U.S. Patent No. 10,899,816 in view of Pavlakis et al (WO 2009/002562 A2; filed 6/27/08; published 12/31/08) is maintained. The rejection of claim 24 is rendered moot by cancellation of the claims.
Although the claims at issue are not identical, they are not patentably distinct from each other.
The instant claims are drawn to an immunocytokine comprising a conjugate comprising a polypeptide comprising the amino acid sequence of IL-15 or a derivative thereof having at least 92.5% sequence identity to SEQ ID NO:3, and a polypeptide comprising the amino acid sequence of IL-15Ralpha having at the amino acid sequence of SEQ ID NO:8 or 9, wherein the il-15 and IL-15Ralpha are separated by a linker sequence. The immunocytokine also comprises an antibody directly linked by covalence or through a linker to the conjugate. The immunocytokine can comprise a conjugate that is a fusion protein. The IL-15 and IL-15Ralpha may or may not be separated by a linker sequence. The sushi domain can have the sequence of SEQ ID NO:8, 9, or 12. The IL-15 can be C-terminal to the sushi domain. The antigen bound by the antibody can be those listed in instant claims 26 and 27. The conjugate can be C-terminal to the antibody. The immunocytokine can be in a pharmaceutical composition with a pharmaceutically acceptable carrier. The claims further comprise a method of treating cancer comprising administering the immunocytokine, wherein the pharmaceutical composition is administered at a dose of 2.5 mg/kg or less.
The reference patent teaches a conjugate comprising a) a conjugate comprising an IL-15 and the sushi domain of an IL-15Ra wherein the conjugate is linked directly or indirectly and covalently to an antibody; and a pharmaceutical composition thereof (see claims 1-5). The conjugate comprises SEQ ID NO:17 for the IL-15/IL-15Ralpha conjugate, and SEQ ID NO:17 comprises a sequence identical to instant SEQ ID NO:12 (sushi domain) followed by a linker, which is followed by a sequence identical to instant SEQ ID NO:3 (see e.g. claim 1 and SEQ ID NO:17 starting in Column 53). The conjugate can be produced in a pharmaceutical composition with a carrier (see e.g. claim 2-4).
The reference patent does not teach linkage of the conjugate with an antibody, the linkage of the conjugate with the antibody wherein the antibody is linked via a linker sequence, wherein the antibody is directed to an antigen such as CEA or HER2.
Pavlakis teaches complexes that comprise IL-15 covalently or noncovalently bound to interleukin-15 receptor alpha ("IL-15Ra") ("IL-15/IL-15Ra complexes") (see e.g. paragraph [0011] and claim 10-13). The IL-15/IL-15Ra complex may comprise native IL-15 or an IL-15 derivative covalently or noncovalently bound to native IL15Ra or an IL-15Ra derivative, with the term “bound” indicating that no linker is present between the peptides (see e.g. paragraph [0011]). The complexes may also comprise a heterologous molecule, such as an antibody that specifically binds to an antigen associated with disease to be treated (see e.g. paragraph [0012] and [0084]-[0085], and claim 15). Non-limiting example antigens include tumor antigens (see e.g. paragraph [0012] and [0084]-[0085]). The heterologous molecule can be conjugated to IL-15 or IL-15Ra, indicating covalent linkage. The IL-15 can comprise SEQ ID NO:1 (see e.g. paragraph [0026]; the sequence of instant SEQ ID NO:3 is underlined):
MRISKPHLRSISIQCYLCLLLNSHFLTEAGIHVFILGCFSAGLPKTEANWVNVISDLKKIEDLIQSMHIDATLYTESDVHPSCKVTAMKCFLLELOVISLESGDASIHDTVENLIILANNSLSSNGNVTESGCKECEELEEKNIKEFLQSFVHIVOMFINTS (SEQ ID NO: 1).
The IL-15Ralpha can comprise SEQ ID NO:3 (see e.g. paragraph [0035]; the sequence of instant SEQ ID NO:8 is underlined; the sequence of instant SEQ ID NO:12 is in bold):
MAPRRARGCRTLGLPALLLLLLLRPPATRGITCPPPMSVEHADIWVKSYSLYSRERYICNSGFKRKAGTSSLTECVLNKATNVAHWTTPSLKCIRDPALVHQRPAPPSTVTTAGVTPQPESLSPSGKEPAASSPSSNNTAATTAAIVPGSQLMPSKSPSTGTTEISSHESSHGTPSQTTAKNWELTASASHQPPGVYPQGHSDTTVAISTSTVLLCGLSAVSLLACYLKSROTPPLASVEMEAMEALPVTWGTSSRDEDLENCSHHL (SEQ ID NO: 3).
Pavlakis teaches that the antigen can comprise CEA, EGFR, HER2, or others (see e.g. paragraph [0084]-[0085]). The complex can be present in a pharmaceutical composition comprising a pharmaceutically acceptable carrier (see e.g. [00149]).
It would have been obvious to one with ordinary skill in the art, at the time of the invention, that the antibody could be an antibody directed to a tumor antigen such as CEA or HER2 because the Supreme Court set forth in KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007), that if the scope and content of the prior art included a similar or analogous product, with differences between the claimed invention and prior art that were encompassed in known variation or in a principle known in the art, and one of ordinary skill in the art could have combined the elements as claimed by known methods, the claimed variation would have been predictable in to one of ordinary skill in the art. Pavlakis provides a complex of IL-15/sushi of IL-15Ralpha using the same amino acid sequences as the reference patent, and indicates that combination of IL-15/sushi conjugates with antibodies that bind to CEA or HER2, among other antigens, is known in the art. Therefore, the differences between the reference patent and Pavlakis were encompassed in known variation or in a principle known in the art. Thus, the combination of prior art references as combined provided a prima facie case of obviousness, absent convincing evidence to the contrary.
Additionally, KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007), discloses that if a technique has been used to improve one method, and a person of ordinary skill would recognize that it would be used in similar methods in the same way, using the technique is obvious unless its application is beyond that person’s skill. It would be obvious to apply a known technique to a known product to be used in a known method that is ready for improvement to yield predictable results. Thus, the combination of prior art references as combined provided a prima facie case of obviousness, absent convincing evidence to the contrary.
Applicant’s Arguments
Applicant argues:
1. Applicant acknowledges the rejections but reserves the right to respond at a later date, upon resolutions of other issues in the Office Action.
Applicant’s arguments have been fully considered and are not persuasive for the following reasons:
Applicant is reminded that a request for a rejection to be held in abeyance does not “distinctly and specifically points out the supposed errors in the examiner’s action” as required under 37 CFR 1.111. See MPEP 714.02. Further, a rejection under double patenting precludes the identification of allowable subject matter. Applicant has not filed a terminal disclaimer, and the claims remain rejected for reasons set forth above.
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Claim Rejections Maintained
Claim Rejections - 35 USC § 112(a)
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
New Matter
Claims 17, 20-21, 23, and 26-33 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
This is a new matter rejection. Applicant has added new limitations to claim 17 which recite “wherein the IL-15 derivative comprises at least one substitution at a position of SEQ ID NO: 3 selected from the positions N71, N72, N77, G78, L45, S51, L52, E64, 168, L69, N65, L52 and N72.” This phrase does not appear in the specification or original claims as filed, and the Examiner also has not been able to locate sufficient support in the specification of any of the parent applications for which priority has been claimed. Applicant has indicated in the arguments filed on 12/23/25 that “Support for substitution at specific positions of SEQ ID NO: 3 is located in WO 2009/135031, as referenced at page 12, line 4 of the present specification, and in WO 2005/085282, as referenced on page 13, line 15 of the present specification.” However, review of these two publications shows that they do not support selection of this set of residues for substitutions. WO 2009/135031 does not name any of the recited mutation locations, and WO 2005/085282 teaches only substitution of an IL-15 mutein at residues 45, 51, 52, 64, 65, 68, and 69. Neither reference identifies these selection of mutations in the sequence of instant SEQ ID NO:3, or in a sequence having 92.5% sequence identity to SEQ ID NO:3.
Applicant does not point out specific basis for this limitation in the application, and none is apparent. The limitations are not expressly asserted in the instant or priority applications, nor do they flow naturally from the specification. Therefore, this limitation is new matter.
Claim Rejections - 35 USC § 112(d)
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 21 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 21 recites an IL-15 with the amino acid sequence of SEQ ID NO:3. However, base claim 17 requires at least one substitution at one of N71, N72, N77, G78, L45, S51, L52, E64, I68, L69, or N65. Claim 17 requires substitution(s) that are not present in the limitations of claim 21, and therefore claim 21 fails to include all the limitations of the claim upon which it depends.
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.
Conclusion
No claim is allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/ANDREA K MCCOLLUM/Examiner, Art Unit 1674
/BRIAN GANGLE/Primary Examiner, Art Unit 1645