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 .
DETAILED ACTION
1. Applicant’s amendments/responses filed 11/9/22 and 2/12/22 are acknowledged and have been entered.
2. Applicant's election without traverse of Group I and species of SEQ ID NO: 15, a fusion protein comprising in N- to -C-terminal order: peptide P12 (SEQ ID NO: 32)-GS linker that is SEQ ID NO: 1, (G4S)3-b2m peptide (SEQ ID NO: 81). It is noted by the Examiner that there is additionally an N-terminal sequence in SEQ ID NO: 15 that is a signal peptide, i.e., MSRSVALAVLALLSLSGLEA or SEQ ID NO: 3, a 20 amino acid signal peptide (see [00379] of the instant specification).
Claims 101-107, 109-113, 115 and 135 read on the elected species.
Accordingly, claims 108 and 114 (non-elected species of Group I) and claims 116-134 (non-elected Groups II-V) are withdrawn from further consideration by the Examiner, 37 CFR 1.142(b), as being drawn to non-elected inventions.
Claims 101-107, 109-113, 115 and 135 are presently being examined as they read upon the elected species and upon the species enunciated below in the art rejections.
Claims 101 and 135 are independent claims.
3. The lengthy specification has not been checked to the extent necessary to determine the presence of all possible minor errors. Applicant’s cooperation is requested in correcting any errors of which Applicant may become aware in the specification.
4. Claim interpretation: The specification discloses at [0087] that the term “presenting peptide” as used herein refers to short peptides that can stably bind to the antigen binding groove of an MHC to form a stable MHC complex that can be recognized by receptors on immune cells. The specification further discloses at [0088] that each MHC has its own matched presenting peptides, and that a presenting peptide that is “restricted” to a particular MHC molecule means that the presenting peptide can form a stable complex with this particular MHC molecule. The specification further discloses at [0082] that MHC complexes include class I MHC molecules that comprise a polymorphic heavy chain (or class I MHC alpha chain), and a light chain which is b2m, and that in humans classic class I MHC include HLA-A, -B and -C and nonclassical class I MHC include HLA-E, -F and -G. The specification discloses at [0084] that the term “b2m peptide” refers to the full length protein of b2m or a functional fragment or variant thereof. The specification further discloses that the mature form of human b2m does not include the signal peptide and consists of 99 amino acid residues and corresponds to the sequence consisting of that depicted in SEQ ID NO: 81. The specification discloses at [0086] that the term “variant” in relation to a protein or a polypeptide refers to a different protein or polypeptide (than the reference protein or polypeptide) comprising one or more amino acid substitutions, deletions, and/or additions as compared to the reference protein or polypeptide, and a functional fragment or variant of a protein or polypeptide maintains the basic structural and functional properties of the reference protein or polypeptide. The specification discloses at [0089] that the term “inhibitory receptor” refers to the receptor molecule expressed on the surface of the immune cell that can inhibit the activity of the immune cells upon binding to its ligand. Also note that the claims are indefinite in the recitation of “less than 500 amino acids or lacks an HLA-E heavy chain” in the context of the rest of the claim limitations as is enunciated below in this office action because the minimum fusion protein is much less than 500 amino acid residues and (not “or”) lacks an HLA-E heavy chain, and because it is not clear if “HLA-E” heavy chain refers to the full length heavy chain or just the HLA-E ECD (extra cellular domain) or both in the absence of a limiting definition therefor in the specification. Note that the fusion protein is not isolated. Also note that there is no limiting definition in the specification for the limitation “about”.
5. 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.
6. Claims 101-106, 109-113, 115 and 135 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 written description rejection.
Applicant has broadly claimed a fusion protein comprising a peptide covalently linked to a b2m peptide via a linker, wherein the presenting peptide is an HLA-E restricted presenting peptide, or a signal peptide of a class I MHC molecule or a fragment thereof, and wherein the fusion protein (1) comprises less than 500 amino acids, or (2) lacks an HLA-E heavy chain, and including the limitations of the dependent claims. In addition, instant dependent claim 115 recites wherein the amino acid sequence of the fusion protein is at least 85%, at least 90%, at least 95%, or 100% identical to an amino acid sequence selected from the recited Markush group of which Applicant’s elected species SEQ ID NO: 15 is present.
The specification does not disclose a representative number of species of such presenting peptides comprised in the fusion protein, including one that when bound to a MHC heavy chain binds an inhibitory receptor of an immune cell, nor the variants of SEQ ID NO: 15 that are at least 85% identical thereto, nor sufficient relevant identifying characteristics in the form of structure or functional characteristics coupled with a known or disclosed correlation between structure and function.
An applicant shows possession of the claimed invention by describing the claimed invention with all of its limitations using such descriptive means as words, structures, figures, diagrams, and formulas that fully set forth the claimed invention. Lockwood v. Amer. Airlines, Inc., 107 F.3d 1565, 1572, 41 USPQ2d 1961, 1966 (Fed. Cir. 1997). Possession may be shown in a variety of ways including description of an actual reduction to practice, or by showing that the invention was "ready for patenting" such as by the disclosure of drawings or structural chemical formulas that show that the invention was complete, or by describing distinguishing identifying characteristics sufficient to show that the applicant was in possession of the claimed invention. See, e.g., Pfaff v. Wells Elecs., Inc., 525 U.S. 55, 68, 119 S.Ct. 304, 312, 48 USPQ2d 1641, 1647 (1998); Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406; Amgen, Inc. v. Chugai Pharm., 927 F.2d 1200, 1206, 18 USPQ2d 1016, 1021 (Fed. Cir. 1991) (one must define a compound by "whatever characteristics sufficiently distinguish it"). "Compliance with the written description requirement is essentially a fact-based inquiry that will ‘necessarily vary depending on the nature of the invention claimed.' " Enzo Biochem, 323 F.3d at 963, 63 USPQ2d at 1612. An invention described solely in terms of a method of making and/or its function may lack written descriptive support where there is no described or art-recognized correlation between the disclosed function and the structure(s) responsible for the function. See MPEP 2163 I.A.
An applicant may also show that an invention is complete by disclosure of sufficiently detailed, relevant identifying characteristics which provide evidence that applicant was in possession of the claimed invention, i.e., complete or partial structure, other physical and/or chemical properties, functional characteristics when coupled with a known or disclosed correlation between function and structure, or some combination of such characteristics. Enzo Biochem, 323 F.3d at 964, 63 USPQ2d at 1613 (quoting the Written Description Guidelines, 66 Fed. Reg. at 1106, n. 49, stating that "if the art has established a strong correlation between structure and function, one skilled in the art would be able to predict with a reasonable degree of confidence the structure of the claimed invention from a recitation of its function".). "Thus, the written description requirement may be satisfied through disclosure of function and minimal structure when there is a well-established correlation between structure and function." See MPEP 2163 II.3.
As is stated in the claim interpretation section of this office action above at item #4,
the specification discloses at [0087] that the term “presenting peptide” as used herein refers to short peptides that can stably bind to the antigen binding groove of an MHC to form a stable MHC complex that can be recognized by receptors on immune cells (instant base claim 101 and its dependent claims), or by inhibitory receptors on immune cells (instant claim 135). Thus, the presenting peptide must possess the functional properties of binding stably to the antigen binding groove of an MHC class I molecule and when so bound must possess the functional property of binding to a cognate receptor or inhibitory receptor on an immune cell. As is also stated in the claim interpretation section, the specification discloses at [0089] that the term “inhibitory receptor” refers to the receptor molecule expressed on the surface of the immune cell that can inhibit the activity of the immune cells upon binding to its ligand. Instant dependent claim 102 recites that the presenting peptide is derived from a virus, a prokaryote, a eukaryote, a mammal, or a human. Dependent claim 103 characterizes the presenting peptide by length range, but not sequence. Dependent claim 104 recites that the presenting peptide is a fragment of a signal peptide of a class I MHC molecule, while claim 105 recites particular human MHC class I molecules (including human non-classical class I molecules). Dependent claim 106 recites a formula sequence for the presenting peptide , wherein the carboxy terminal amino acid at position 9 is leucine, but wherein the other positions are variable by two to five different defined amino acid residues. Dependent claims 109-113 recite features of length, linker or b2m. Independent claim 135 recites a generic presenting peptide.
The specification further discloses at [0088] that each MHC has its own matched presenting peptides, and that a presenting peptide that is “restricted” to a particular MHC molecule means that the presenting peptide can form a stable complex with this particular MHC molecule. The specification further discloses at [0082] that MHC complexes include class I MHC molecules that comprise a polymorphic heavy chain (or class I MHC alpha chain, and a light chain which is b2m, and in humans classic class I MHC include HLA-A, -B and -C and nonclassical class I MHC include HLA-E, -F and -G.
The specification discloses a number of presenting peptides at [00142], some of which fall into the subgenus formula recited in dependent claim 106; however, others do not, and the examples at said paragraph are at a minimum missing those that start with an isoleucine “I”. Since the presenting peptides must possess the functional property of binding to HLA-E or must be a signal peptide or a fragment of a signal peptide from any class I MHC molecule that must also possess the functional property of binding to any MHC class I molecule and may derive from any protein, it is clear that the genus of such presenting peptides encompassed by the instant claims is much broader than that disclosed in the specification or the art.
The art recognizes that MHC class I molecules, and particularly human (HLA) class I molecules are highly polymorphic and most of the polymorphisms affect the peptide binding site or region thereof, as is taught by evidentiary reference Kremer et. al., (Stem Cells International, 2015, article ID 346714, pages 1-12, see entire reference), the further teachings of which are enunciated herein. Although HLA-E (two alleles of HLA-E that predominantly contribute to immune function) can bind to some signal peptides from classical class I molecules, it is also recognized that a larger repertoire of peptides can be presented by HLA-E. On the surface of healthy cells, HLA-E can present a limited set of highly conserved hydrophobic peptides derived from classical class I MHC leader peptide sequences, and these complexes thereof are ligands for the NKG2/CD94 receptor family of human NK cells, in particular the inhibitory NKG2A/CD94 and the stimulatory NKG2C/CD94 receptors. In the case of cells undergoing cellular stress, HLA-E presents fragments of heat shock proteins and these complexes of HSP peptide/HLA-E inhibit the binding to the NKG2A/CD94 receptor, leading to NK cell mediated lysis. The peptide VMAPRTLIL, derived from the UL40 protein of HCMV mimics the signal sequence peptide present in most HLA-C allotypes, and the resulting complex is able to circumvent NK cell mediated lysis by serving as a ligand for the NKG2A/CD94 receptor. NKG2/CD94 receptors distinguish subtle differences in the amino acid sequences of the bound peptides, however, the mechanism of how certain complexes activate or inhibit NK or T cell responses is not completely understood. An example of this is the VMAPRTLFL peptide derived from HLA-G, wherein subtle changes in this peptide can influence interaction between the inhibitory and activating NKG2/CD94 receptors. Table 1 of the said evidentiary reference shows examples of canonical HLA-E peptide ligands as well as non-canonical peptide ligand of unusual length, the latter having no conserved features amongst themselves, and some of which are protective and some of which are not with regard to target cell lysis (i.e., bind to HLA-E but when so bound, do not possess the functional property of binding to an inhibitory receptor on an immune cell). In addition, even if a peptide can bind to a MHC molecule such as HLA-E, there is no correlation with the ability of the resulting peptide/MHC complex (that is, the functional property) to bind an inhibitory receptor on an immune cell, including one on an NK cell such as CD94/NKG2A. In addition with further regard to claim 135, the specification does not disclose a genus of inhibitory receptors on immune cells except for CD94/NKG2A on NK cells and on some T cells, nor does the specification disclose a structure/function relationship for the said genus or for the presenting peptide/MHC class I, as some presenting peptides correlate to inhibitory activity through CD94/NKG2A, while others do not.
The specification also does not provide a representative number of species of variants of SEQ ID NO: 15 that are at least 85% identical thereto that comprises variants of a presenting peptide comprised in SEQ ID NO: 15 (i.e., in this instance a variant of VMAPRTLFL (SEQ ID NO: 32) that in concert with other additions, deletions, or substitutions in the sequence of SEQ ID NO: 15 allow for the functional property of the subsequence thereof to be a “presenting peptide” that binds to HLA-E or that is a fragment of a signal peptide of a class I MHC molecule that has the functional property of being a “presenting peptide”.
Therefore, it appears that the instant specification does not adequately disclose the breadth of the presenting peptides or the fusion protein variant recited in the instant claims. In light of this, a skilled artisan would reasonably conclude that Applicant was not in possession of the genus of all such fusion proteins at the time the instant application was filed.
7. 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.
8. Claims 101-107, 109-113, 115 and 135 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.
a) A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, claim 109 recites the broad recitation ”wherein the fusion protein has (1) less than 500, and the claim also recites “less than 400, less than 300, or less than 200 amino acids” which is the narrower statement of the range/limitation. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
b) (i) Claim 101 is indefinite in the recitation of “wherein the fusion protein (1) comprises less than 500 amino acids, or (2) lacks an HLA-E heavy chain” in the context of the other limitations of the claim because it is not clear what is meant, i.e., at a minimum, the fusion protein can comprise a presenting peptide (canonical length 9 amino acid residues, although longer non-canonical HLA-E binding peptides about twice as long are encompassed) linked covalently to a b2m peptide (for example, the mature form of human b2m does not include the signal peptide and consists of 99 amino acid residues and corresponds to the sequence consisting of that depicted in SEQ ID NO: 81 acid residues in length) via a linker. The length of this fusion protein (110 amino acids) is much less than 500 amino acid residues AND (not “or”) it also lacks an HLA-E heavy chain.
b)(ii) In addition, it is not clear if the limitation “lacks an HLA-E heavy chain” recited in claim 101 refers to both the full length HLA-E heavy chain or the extracellular region thereof or both.
c) Claim 115 is indefinite in the recitation of “wherein the amino acid sequence of the fusion protein is at least 85%, at least 90% or 100% identical to an amino acid sequence selected from the group consisting of” the recited SEQ ID NOs (which includes Applicant’s elected species of SEQ ID NO: 15). These said sequences are 143 or 144 amino acid residues in length (that is, they comprise less than 500 amino acids AND lack an HLA-E heavy chain). (In the interest of compact prosecution, Applicant is advised that at the lower percent amino acid sequence identity (85%), potentially 21 amino acid residues could be added to the 143 already comprised therein and it still would be much less than 500 amino acid residues in length AND lack an HLA-E heavy chain.)
d). Claim 135 is indefinite in the recitation of “wherein the fusion protein comprises (1) less than 500 amino acids, or (2) lacks an HLA-E heavy chain” in the context of the rest of the claim because it is not clear what is meant, i.e., at a minimum, the fusion protein is much less than 500 amino acid residues in length AND it also lacks an HLA-E heavy chain. In addition, it is not clear if the limitation “lacks an HLA-E heavy chain” recited in claim 101 refers to both the full length HLA-E heavy chain or the extracellular region thereof or both.
e) Claim 109 is indefinite in the recitation of “about” because it is not clear what is meant in the absence of a limiting definition in the specification therefore.
9. 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.
10. For the purpose of prior art rejections, the filing date of the instant claims is deemed to be the filing date of PCT/ CN2019/124321, i.e., 12/10/19, as China 201910746355.8 is not in the English language and no certified translation has been filed by Applicant.
11. Independent claim 101 recites: A fusion protein comprising a presenting peptide covalently linked to a beta-2- microglobulin (b2M) peptide via a linker, wherein the presenting peptide is an HLA-E- restricted presenting peptide, or a signal peptide of a Class I MHC molecule or a fragment thereof, and wherein the fusion protein (1) comprises less than 500 amino acids, or (2) lacks an HLA-E heavy chain.
Independent claim 135 recites: A fusion protein comprising a presenting peptide covalently linked to a beta-2-microglobulin (b2M) peptide via a linker, wherein the fusion protein binds a major histocompatibility (MHC) heavy chain to form an MHC complex that binds an inhibitory receptor of an immune cell to inhibit the immune cell, and wherein the fusion protein (1) comprises less than 500 amino acids, or (2) lacks an HLA-E heavy chain.
12. 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)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
13. Claims 101-107, 109-113, 115 and 135 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by US2021/0268028 A1 (pgPub of 17/256,434, priority to at least 6/14/19) or WO 2020/007593 A1 (PCT/EP2019/065761, priority to at least 6/14/19), as evidenced by Kremer et. al. (Stem Cells International, 2015, article ID 346714, pages 1-12).
US2021/0268028 A1 discloses a fusion protein (SEQ ID NO: 37) that comprises a portion that is identical to instantly recited SEQ ID NO: 15 (see entire reference, especially Table 15 at the entry for SEQ ID NO: 37 and titled “NK inhibitor 2”, and sequence listing).
WO 2020/007593 A1 teaches the same sequence SEQ ID NO: 37 (at Table 15) and that it is “NK inhibitor 2). See entire reference.
Although the art reference sequence is 500 amino acid residues in length, it lacks an HLA-E heavy chain, thus meeting the claim limitations.
With regard to instant claim 135 and the recitation of “wherein the fusion protein binds a MHC heavy chain to form an MHC complex that binds an inhibitory receptor of an immune cell to inhibit the immune cell”, the art reference discloses that the sequence is an NK inhibitor (e.g., at figure 2C for US2021/0268028 A1 or Table 15 of WO 2020/007593 A1) and evidentiary reference Kremer et. al. teaches that when the peptide VMARPTLFL binds to HLA-E, the complex thereof binds to the NKG2A/CD94 inhibitory receptor on NK cells (see entire reference, especially second paragraph prior to section 2 and the first full paragraph on page 2).
The identity of the two sequences is shown below with “Qy” being instantly recited SEQ ID NO: 15 and “Db” depicting the portion of the art sequence that is identical to SEQ ID NO: 15 (i.e., the portion of SEQ ID NO: 37 of the art reference that is identical to instantly recited SEQ ID NO: 15):
Sequence 37, US/17256434
CURRENT APPLICATION NUMBER: US/17/256,434
CURRENT FILING DATE: 2020-12-28
PRIOR APPLICATION NUMBER: PCT/EP2019/065761
PRIOR FILING DATE: 2019-06-14
NUMBER OF SEQ ID NOS: 48
SEQ ID NO 37
LENGTH: 500
TYPE: PRT
ORGANISM: Homo sapiens
Query Match 100.0%; Score 752; Length 500;
Best Local Similarity 100.0%;
Matches 143; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 MSRSVALAVLALLSLSGLEAVMAPRTLFLGGGGSGGGGSGGGGSIQRTPKIQVYSRHPAE 60
Db 1 MSRSVALAVLALLSLSGLEAVMAPRTLFLGGGGSGGGGSGGGGSIQRTPKIQVYSRHPAE 60
Qy 61 NGKSNFLNCYVSGFHPSDIEVDLLKNGERIEKVEHSDLSFSKDWSFYLLYYTEFTPTEKD 120
Db 61 NGKSNFLNCYVSGFHPSDIEVDLLKNGERIEKVEHSDLSFSKDWSFYLLYYTEFTPTEKD 120
Qy 121 EYACRVNHVTLSQPKIVKWDRDM 143
Db 121 EYACRVNHVTLSQPKIVKWDRDM 143
It also bears repeating the instantly recited SEQ ID NO: 15 comprises in N-to-C-terminal order: MSRSVALAVLALLSLSGLEA or SEQ ID NO: 3 (a 20 amino acid signal peptide (see [00379 of the instant specification)- covalently linked to peptide P12 (SEQ ID NO: 32 or VMAPRTLFL from HLA-G)- covalently linked to the GS linker SEQ ID NO: 1 consisting of the sequence (G4S)3- covalently linked to the b2m peptide (SEQ ID NO: 81).
14. Claims 101-107, 109-113, 115 and 135 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by WO2020097188 A1 (priority to at least 11/6/19), as is evidenced by A_Geneseq_202544 BHU30189 (2020, 2 pages) shown below.
Note that the art reference sequence is 477 amino acid residues in length and lacks an HLA-E heavy chain as is evidenced by evidentiary reference A_Geneseq_202544 BHU30189 (2020) shown below.
WO2020097188 A1 teaches a sequence that comprises a sequence that is identical to instantly recited SEQ ID NO: 15 that inhibits NK mediated cell killing (see entire reference, especially Table A at SEQ ID NO: 8 (second entry in the table)). Instantly recited SEQ ID NO: 15 is depicted below as “Qy”, while the portion of the art reference sequence that is identical to instantly recited SEQ ID NO: 15 is depicted below as “Db”.
A_Geneseq_202544 BHU30189
ID BHU30189 standard; protein; 477 AA.
XX
AC BHU30189;
XX
DT 09-JUL-2020 (first entry)
XX
DE HLA-G trimer protein, SEQ ID 8.
XX
KW HLA class I antigen alpha G; HLA-G protein; autoimmune disease; cancer;
KW cytostatic; immunosuppressive; protein identification; protein therapy;
KW screening; therapeutic.
XX
OS Homo sapiens.
XX
CC PN WO2020097188-A1.
XX
CC PD 14-MAY-2020.
XX
CC PF 06-NOV-2019; 2019WO-US060045.
XX
PR 06-NOV-2018; 2018US-0756411P.
XX
CC PA (SAGM ) SANGAMO THERAPEUTICS INC.
XX
CC PI Conway A, De Almeida P, Jain S, Spelman M;
XX
DR WPI; 2020-42031S/042.
XX
CC PT Identifying molecule that reduces or prevents natural killer (NK)-
CC PT mediated killing of donor cell involves e.g. incubating genetically
CC PT modified donor cells of molecule with effector NK cells and incubating
CC PT cell mixture with dye and antibody.
XX
CC PS Disclosure; SEQ ID NO 8; 118pp; English.
XX
CC The present invention relates to a method for identifying a molecule that
CC reduces or prevents natural killer (NK)-mediated killing of a donor cell.
CC The method involves (a) incubating genetically modified donor cells
CC comprising the molecule with effector NK cells; (b) incubating the cell
CC mixture of step (a) cells with at least one dye and an antibody that
CC binds to cleaved caspase-3, where the dyes preferentially accumulate in
CC live or dead cells; (c) analyzing the donor cells for viability based on
CC accumulation of the dyes; and (d) analyzing apoptosis in the donor cells
CC by evaluating cleaved caspase-3 levels, where an increase of live or non-
CC apeptotic genetically modified donor cells as compared to control cells
CC is indicative that the molecule reduces or prevents NK- mediated killing
CC of the donor cell. The invention also provides: a molecule identified by
CC the method, where the molecule is a protein expressed on the cell surface
CC of the donor cell; and a composition comprising a population of donor
CC cells and at least one molecule. The method of the invention is useful
CC for treating cancer, autoimmune disease, or a tissue or cell graft.
XX
SQ Sequence 477 AA;
Query Match 100.0%; Score 752; Length 477;
Best Local Similarity 100.0%;
Matches 143; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 MSRSVALAVLALLSLSGLEAVMAPRTLFLGGGGSGGGGSGGGGSIQRTPKIQVYSRHPAE 60
Db 1 MSRSVALAVLALLSLSGLEAVMAPRTLFLGGGGSGGGGSGGGGSIQRTPKIQVYSRHPAE 60
Qy 61 NGKSNFLNCYVSGFHPSDIEVDLLKNGERIEKVEHSDLSFSKDWSFYLLYYTEFTPTEKD 120
Db 61 NGKSNFLNCYVSGFHPSDIEVDLLKNGERIEKVEHSDLSFSKDWSFYLLYYTEFTPTEKD 120
Qy 121 EYACRVNHVTLSQPKIVKWDRDM 143
Db 121 EYACRVNHVTLSQPKIVKWDRDM 143
15. The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
16. Court rulings have been quite clear that ONLY DIVISIONAL applications are entitled to the shield from double patenting under 35 USC 121. Indeed, in AMGEN INC v. HOFFMANN LA ROCHE LTD GMBH LA (Nos. 2009-1020, 2009-1096) the court discusses this issue at length and states:
Turning to the legislative history, the court observed that a House Report also referred specifically to “divisional application[s].” Id. Notably absent from the legislative history, in the court's view, was a suggestion “that the safe-harbor provision was, or needed to be, directed at anything but divisional applications.” Id. at 1361. From there, the court “conclude^] that the protection afforded by section 121 to applications (or patents issued therefrom) filed as a result of a restriction requirement is limited to divisional applications.” Id. at 1362. Accordingly, the court decided that the § 121 safe harbor did not apply to the patent before it, which issued from a continuation-in-part application. Id.
We are persuaded by the reasoning in Pfizer that the § 121 safe harbor provision does not protect continuation applications or patents descending from only continuation applications. The statute on its face applies only to divisional applications, and a continuation application, like a continuation-in-part application, is not a divisional application.
Given that Applicant chose to file the 18/294,928 case as a separate unrelated application, not as a DIV of the instant application, the instant rejection has been set forth.
Claims 101-107, 109-113 and 135 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3, 5, 12-14, 16, 17, 28, 30, 34-36, 39, 42, 43, 47, 50, 51, 62-64, 74, 116, 123, 141, 147, 155, 157, 158 and 160-163 of copending Application No. 18/294,928.
Claims 1-3, 5, 12-14, 16, 17, 28, 30, 34-36, 39, 42, 43, 47, 50, 51, 62, 63 and 155 of 18/294,928 are drawn to a modified cell comprising a fusion protein comprising VMAPRTLFL (SEQ ID NO: 29 of ‘928 that is identical to instantly recited SEQ ID NO: 32), a glycine serine linker that is (G4S)3 (SEQ ID NO: 99 of ‘928 that is identical to instantly recited SEQ ID NO: 1), and mature b2m, and wherein the fusion protein that forms a complex is capable of inhibiting an immune cell. The fusion protein may also comprise a signal sequence peptide.
Claims 63, 74, 116, 123, 141, 147 and 161 of 18/294,928 are drawn to a nucleic acid sequence encoding the said fusion protein/pharmaceutical composition thereof and a method for preparing the modified cell by inserting the said polynucleotide into a cell.
Claims 157 and 158 of 18/294,928 are drawn to a method for allogeneic transplantation comprising administering the said modified cell.
Claim 160 of 18/294,928 is drawn to a method for treating a tumor comprising administering the modified cell.
Claim 162 of 18/294,928 is drawn to a method for allogenic transplantation comprising administering the isolated nucleic acid molecule.
Claim 163 of 18/294,928 is drawn to a method for treating a tumor comprising administering the isolated nucleic acid molecule.
Note that the fusion protein has the same peptide and linker as well as a mature b2m. An obvious variant of a mature b2m is human b2m (such as that recited in instant claim 113 that is 100% identical to instantly recited SEQ ID NO: 81). Therefore with regard to instant claim 113, it would have been prima facie obvious to one of ordinary skill in the art before the filing date of the claimed invention to have used mature human b2m as the mature b2m in the fusion protein. One of ordinary skill in the art would have been motivated to do this, and with a reasonable expectation of success in doing so, in order to make a composition for human use. Note that the fusion protein is 123 amino acid residues (9-mer signal sequence peptide-15 amino acid residue linker-human mature b2m of 99 amino acid residues in length). Note that the fusion protein recited in the claims of 18/294,928 is not isolated. None-the-less, it would have been prima facie obvious to one of ordinary skill in the art to have made an isolated version of the fusion protein as per the teaching of IDS reference Tafuro et. al. (Eur. J. Immunol. 2001, 31: 440-449, IDS reference) who teach that an epitope peptide linked to the N-terminus of human b2m refolded efficiently in vitro and could be used to bind specifically to cognate immune cells when multimerized with a class I MHC heavy chain (see entire reference). One of ordinary skill in the art would have been motivated to do this, and with a reasonable expectation of success in doing so, for that reason. Alternatively, it would have been prima facie obvious to one of ordinary skill in the art to have made an isolated version of the fusion protein as per the teaching of IDS reference Uger et. al. (J. Immunol. 1999, 162: 6024-6028, IDS reference) as Uger et. al. teach that tethering peptide epitopes to human b2m and expressed recombinantly result in enhanced MHC stabilization as compared with the uncoupled counterpart peptide/b2m. One of ordinary skill in the art would have been motivated to do this, and with a reasonable expectation of success in doing so, for that reason.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 101-107, 109-113 and 135 are directed to an invention not patentably distinct from claims 1-3, 5, 12-14, 16, 17, 28, 30, 34-36, 39, 42, 43, 47, 50, 51, 62-64, 74, 116, 123, 141, 147, 155, 157, 158 and 160-163 of commonly assigned 18/294,928, as enunciated supra.
The U.S. Patent and Trademark Office may not institute a derivation proceeding in the absence of a timely filed petition. The USPTO normally will not institute a derivation proceeding between applications or a patent and an application having common ownership (see 37 CFR 42.411). Commonly assigned 18/294,928, discussed above, may form the basis for a rejection of the noted claims under 35 U.S.C. 102 or 103 if the commonly assigned case qualifies as prior art under 35 U.S.C. 102(a)(2) and the patentably indistinct inventions were not commonly owned or deemed to be commonly owned not later than the effective filing date under 35 U.S.C. 100(i) of the claimed invention.
In order for the Examiner to resolve this issue the applicant or patent owner can provide a statement under 35 U.S.C. 102(b)(2)(C) and 37 CFR 1.104(c)(4)(i) to the effect that the subject matter and the claimed invention, not later than the effective filing date of the claimed invention, were owned by the same person or subject to an obligation of assignment to the same person. Alternatively, the applicant or patent owner can provide a statement under 35 U.S.C. 102(c) and 37 CFR 1.104(c)(4)(ii) to the effect that the subject matter was developed and the claimed invention was made by or on behalf of one or more parties to a joint research agreement that was in effect on or before the effective filing date of the claimed invention, and the claimed invention was made as a result of activities undertaken within the scope of the joint research agreement; the application must also be amended to disclose the names of the parties to the joint research agreement.
A showing that the inventions were commonly owned or deemed to be commonly owned not later than the effective filing date under 35 U.S.C. 100(i) of the claimed invention will preclude a rejection under 35 U.S.C. 102 or 103 based upon the commonly assigned case. Alternatively, applicant may take action to amend or cancel claims such that the applications, or the patent and the application, no longer contain claims directed to patentably indistinct inventions.
17. Claims 101, 104 and 105 are objected to because of the following informalities: “Class” in “Class I MHC” should be lower case. Appropriate correction is required.
18. No claim is allowed.
19. Any inquiry concerning this communication or earlier communications from the examiner should be directed to MARIANNE DIBRINO whose telephone number is (571)272-0842. The examiner can normally be reached on M, T, Th, F.
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/Marianne DiBrino/
Marianne DiBrino, Ph.D.
Patent Examiner
Group 1640
Technology Center 1600
/MICHAEL SZPERKA/Primary Examiner, Art Unit 1641