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 .
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 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.
DETAILED ACTION
Claims 1-13 are pending in the instant application.
Priority
This application is a 371 of PCT/CN2021/076670, filed on 2/18/2021 which claims priority to the Chinese application CN202011642917.3 filed on 12/30/2020.
Information Disclosure Statement
The information disclosure statements (IDS) dated 7/11/2023, 9/15/2023, 2/5/2024, 1/13/2025, 3/5/2025, 4/16/2025, 5/27/2025,6/12/2025, and 3/23/2026 comply with the provisions of 27 CFR 1.97, 1.98, and MPEP § 609. Accordingly, they have been placed in the application file and the information therein has been considered as to the merits.
Claim Interpretation
The term “functional fragment” of IL-15 was interpreted according to the instant specification as:
“The IL-15 functional fragment in the present invention refers to a cytokine of about 12-14 kD discovered by Grabstein et al. in 1994 (J G Giri et al., EMBO J. 1994 Jun 15; 13(12): 2822-2830.), which can function in the normal immune response of the body, e.g., to promote the proliferation of T cells, B cells and NK cells.” (pg 5, para 0017).”
Objections to the Claims
Claim 7 contains mixed verb tenses. Please replace “(c) subjecting (a) and (b) to co-transfection expression, or to separate expression followed by protein assembly in vitro” with “(c) subjecting (a) and (b) to co-transfection expression, or separating expression followed by protein assembly in vitro”.
Claim 11 contains the unnecessary phrase “any of” to describe a selection wherein there is only one option. Please replace “of any of the” with “of the".
Claim 13 uses the conjunction “and” wherein the conjunction “and/or” would clarify that the detection kit can be used to detect tumor cells in the absence of pathogens (and vice versa).
Correction is required. See MPEP § 608.01(m).
Claim Rejections – 35 USC § 112(b)
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1-13 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
All except 9-10, 13
The term “long-acting” in claims 1-8 and 11-12 is a relative term which renders the claim indefinite. The term “long-acting” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. Furthermore, it is unclear if “long-acting” is merely referring to the half-life of the molecule before it is degraded or if this term is referring to how long the fusion protein remains bound and how long it exerts its effects. Dependent claims 9-10 and 13 fail to cure these deficiencies, thus are also rendered indefinite.
Claim 13
Claim 13 is drawn to a product (a detection kit) with an intended use (“used for detecting pathogens and tumor cells). MPEP § 2111.02 (II) states:
“During examination, statements in the preamble reciting the purpose or intended use of the claimed invention must be evaluated to determine whether or not the recited purpose or intended use results in a structural difference (or, in the case of process claims, manipulative difference) between the claimed invention and the prior art. If so, the recitation serves to limit the claim…
“The recitation of the intended use of “detecting” a vitamin deficiency in the preamble rendered the claimed invention a method for “detecting,” and, thus, was not limited to detecting “elevated” levels…
“…a preamble generally is not limiting when the claim body describes a structurally complete invention such that deletion of the preamble phrase does not affect the structure or steps of the claimed invention.” Consequently, “preamble language merely extolling benefits or features of the claimed invention does not limit the claim scope without clear reliance on those benefits or features as patentably significant.”)”
In the instant case, the stated intended use does not materially modify the structure of the kit, thus was found to not limit the claim scope. As a result, this claim is rendered indefinite for implying a method that fails to recite steps to perform, whilst also being a product claim. See MPEP § 2173.05(q).
Claim 11
Claim 11 is drawn to “an effective prophylactic or therapeutic dose” of the fusion protein wherein it is unclear how a “prophylactic dose” differs from a “therapeutic dose”. The instant specification appears to define these dosages as containing the same amount of fusion protein (instant spec pg 6, para 0024; pg 13, para 0062). This claim is rendered indefinite because it is not clear what makes a dosage “prophylactic” versus “therapeutic” if the amounts of fusion protein are the same. One practitioner may assume the difference is in the route of administration, where prophylactic doses are administered systemically, whereas therapeutic doses are administered locally (i.e. at the tumor site). Another practitioner may presume prophylactic compositions comprise additional components (i.e. adjuvants) that are not required in therapeutic applications. As a result of these multiple interpretations, this claim is rendered indefinite. Examiner recommends using the broader language of “therapeutically effective amount” (recited in instant spec pg 13, para 0062) which encompasses all medical uses of the fusion protein. More specifically, Examiner recommends replacing “an effective prophylactic or therapeutic dose of any of the” with “a therapeutically effective amount of the”.
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.
Claims 12-13 are 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 12-13
Claim 13 is drawn to a detection kit comprising no other components other than the fusion protein described in parent claim 1. Thus claim 13 fails to further limit parent claim 1. Dependent claim 14 further adds an intended use for this kit, which fails to cure this deficiency. As a result, claim 13 also fails to further limit parent claim 12.
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 § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 1-2, 4, and 6-13 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Jones (US20200155662).
Claim 1-2,4,6,8
Regarding claims 1-2, 4, 6, and 8, Jones teaches a protein and a nucleic acid encoding a protein comprising a IL-15RαSu/Fc fusion domain and a IL-15 superagonist complex (pg 1, para 0004; pg 1, para 0006) wherein the domains are bound covalently (pg 44, para 0326). Jones teaches the IL-15RαSu/Fc/IL-15 superagonist complex comprises the (i) IL-15 functional fragment of instant SEQ ID NO: 4; (ii) the IL-15 receptor α sushi domain (IL-15RαSu) of instant SEQ ID NO: 3; and (3) the entirety of the Fc domain of instant SEQ ID NO: 1. Note, instant SEQ ID NO: 2 which is a more specific version of SEQ ID NO: 1 has been shown below with the variable residues within instant SEQ ID NO: 1 underlined.
instant_4 --------------------NWVNVISDLKKIEDLIQSMHIDATLYTESDVHPSCKVTAM 40
Jones_110 METDTLLLWVLLLWVPGSTGNWVNVISDLKKIEDLIQSMHIDATLYTESDVHPSCKVTAM 60
****************************************
instant_4 KCFLLELQVISLESGDASIHDTVENLIILANDSLSSNGNVTESGCKECEELEEKNIKEFL 100
Jones_110 KCFLLELQVISLESGDASIHDTVENLIILANDSLSSNGNVTESGCKECEELEEKNIKEFL 120
************************************************************
instant_4,3 QSFVHIVQMFINTS----------------------------------------ITCPPP 114,6
Jones_110 QSFVHIVQMFINTSGSGEGRGSLLTCGDVEENPGPMDRLTSSFLLLIVPAYVLSITCPPP 180
************** ******
instant_3 MSVEHADIWVKSYSLYSRERYICNSGFKRKAGTSSLTECVLNKATNVAHWTTPSLKCIR- 65
Jones_110 MSVEHADIWVKSYSLYSRERYICNSGFKRKAGTSSLTECVLNKATNVAHWTTPSLKCIRE 240
***********************************************************
instant_2 --------------APELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFN 46
Jones_110 PKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFN 300
**********************************************
instant_2 WYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTI 106
Jones_110 WYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTI 360
************************************************************
instant_2 SKAKGQPREPQVYTSPPSRDELTKNQVSLRCHVKGFYPSDIAVEWESNGQPENNYKTTKP 166
Jones_110 SKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPP 420
************** ************** * ************************** *
instant_2 VLDSDGSFFLYSDLTVDKSRWQQGNVFSCSVYHEALHNHYTQKSLSLSPGK 217
Jones_110 VLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK 471
************.****************** *******************
In Jones’ SEQ ID NO: 110 shown above, the C-terminus of the IL-15RαSu domain is linked to the Fc domain.
claim 7
Regarding claim 7, Jones teaches linking an Fc monomer to the IL-15RαSu domain via a peptide linker sequence (pg 1, para 0006; pg 4, para 0313). Jones teaches a nucleic acid encoding a IL-15RαSu/Fc/IL-15 superagonist complex (pg 1, para 0004; pg 1, para 0006). Jones teaches:
“…some embodiments provide polynucleotides that encode target antigens from any source as described further herein, vectors comprising such polynucleotides and host cells transformed or transfected with such expression vectors. In order to express a desired target antigen polypeptide, nucleotide sequences encoding the polypeptide, or functional equivalents, can be inserted into an appropriate Ad vector (e.g., using recombinant techniques). The appropriate adenovirus vector may contain the necessary elements for the transcription and translation of the inserted coding sequence and any desired linkers. Methods which are well known to those skilled in the art may be used to construct these adenovirus vectors containing sequences encoding a polypeptide of interest and appropriate transcriptional and translational control elements. These methods include in vitro recombinant DNA techniques, synthetic techniques, and in vivo genetic recombination.” (pg 15, para 0145).
Jones teaches the polynucleotides of the invention can be may be combined with other DNA sequences, such as promoters, expression control sequences, polyadenylation signals, additional restriction enzyme sites, multiple cloning sites, other coding segments, and the like” (pg 16, para 0149). Jones teaches co-expression strategies that separate the IL-15 functional fragment from the IL-15RαSu/Fc domain can be performed to produce proteins at high levels in a soluble, stable complex (pg 27, para 0235). In sum, this satisfies the limitations of (a) an Fc monomer to the IL-15RαSu domain via a peptide linker sequence; (b) obtaining an IL-15 functional fragment; and (c) to subject (a) and (b) to a co-transfection expression and “to separate expression followed by protein assembly in vitro.”
Claim 9
Regarding claim 9, Jones teaches a plasmid encoding the nucleic acid comprising the IL-15RαSu/Fc/IL-15 superagonist complex (pg 48, para 0359; pg 10, para 0104).
Claim 10
Regarding claim 10, Jones teaches a host cell comprising the plasmid (pg 15, para 0142-0145; pg 16, para 0153).
Claim 11
Regarding claim 11(1), Jones teaches a composition comprising a pharmaceutically acceptable carrier and the IL-15RαSu/Fc/IL-15 superagonist complex (pg 36; para 0310; pg 42, para 0315-0316).
Claim 11
Regarding claims 11(8) or 11(9), Jones teaches a composition comprising a pharmaceutically acceptable carrier and the vector which comprises the nucleic acid which encodes the IL-15RαSu/Fc/IL-15 superagonist complex (pg 42, para 0315-0316).
Claim 12
Regarding claim 12, Jones teaches a kit comprising the IL-15RαSu/Fc/IL-15 superagonist complex (pg 53, para 0393). Because the instantly claimed kit comprises no other components other than this protein, this satisfies the limitations of being a “detection kit”.
Claim 13
Regarding claim 13, Jones teaches the IL-15RαSu/Fc/IL-15 superagonist complex can be used to generate an immune response that targets an infectious agent or cancer (pg 47, para 0354). Jones teaches blood or fluid samples may be assayed to detect the cell-mediated immune response towards infectious agents or cancer (pg 47; para 0354). Jones teaches such immune responses can be monitored to assess the progression of infected cells or tumors within patients (pg 48, para 0357). In sum, this satisfies the limitations of a detection kit that can be used to detect pathogens and tumor cells.
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 1-4 and 6-13 are rejected under 35 U.S.C. 103 as being unpatentable over Jones (US20200155662) as applied to claims 1-3 and 6-13 above, and further in view of Mortier (doi: 10.1074/jbc.M508624200).
*claim 3
Regarding claim 3, Jones teaches the IL-15RαSu domain is linked to the Fc domain via a linker peptide (SEQ ID NO: 110). Jones teaches the domains within the protein can be separated by a linker sequence (pg 4, para 0313; pg 15, para 0145), wherein the linker is optionally SEQ ID NO: 92, GGSGGSGGSGG.
Jones does not teach the linker peptide is GGGGS or (GGGGS)3.
Mortier teaches Fusion proteins of IL-15 and IL-15Rα-sushi are more potent agonists when attached by a flexible linker (abstract; pg 1613, col 1, para 2). Mortier teaches flexible linkers comprising repetitions of GGGGS are exemplary flexible linkers, exemplifying the sequence SGGGSGGGGSGGGGSGGGGSGGGSLQ (pg 1613, col 2, para 1).
It would have been obvious to combine the teachings of Jones and Mortier because Jones teaches the linker can comprise three repeats of three repeats of GGS and Mortier teaches that linkers comprising three repeats of GGGGS are flexible. One of skill in the art would have had a reasonable expectation of success because Mortier teaches that flexible linkers comprising three repeats of GGGS generates more potent IL-15/IL-15Rα-sushi fusion proteins and Jones teaches the L-15/IL-15RαSu/Fc fusion protein can comprise three repeats of a GGS-containing linker.
Relevant Prior Art
Chen (US20190367611) teaches monomeric human IgG1 Fc domains that can be used in fusion proteins (abstract). Chen teaches these Fc domains can comprise mutations e.g. T366 and Y407 (claim 5), however Chen does not teach the Fc domain variant which comprises the selection of mutations within instant SEQ ID NO: 2.
Allowable Subject Matter
Claim 5 is objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form, including all of the limitations of the base claim and any intervening claims.
Claim 5
Instant SEQ ID NO: 2 was not found in the prior art. The closest prior art is that of Jones (US20200155662), shown below.
instant_2 --------------APELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFN 46
Jones_110 PKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFN 300
**********************************************
instant_2 WYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTI 106
Jones_110 WYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTI 360
************************************************************
instant_2 SKAKGQPREPQVYTSPPSRDELTKNQVSLRCHVKGFYPSDIAVEWESNGQPENNYKTTKP 166
Jones_110 SKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPP 420
************** ************** * ************************** *
instant_2 VLDSDGSFFLYSDLTVDKSRWQQGNVFSCSVYHEALHNHYTQKSLSLSPGK 217
Jones_110 VLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK 471
************.****************** *******************
Absent the teaching to perform the specified mutations of the Fc mutation to generate that of instant SEQ ID NO: 2, one of skill in the art would not have been motivated to generate this sequence.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to LAURA ANN ESSEX whose telephone number is 571-272-1103. The examiner can normally be reached Mon - Fri 8:30-5:00.
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/L.A.E./
Examiner, Art Unit 1675
/JEFFREY STUCKER/Supervisory Patent Examiner, Art Unit 1675
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