DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Status of the Claims
Claims 1-13 are pending.
Claim 1 is newly amended.
Claims 10-13 are newly added.
Claims 5-7 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention or species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 09/25/2025.
Claims 1-4 and 8-13 have been examined on their merits.
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 08/25/2026 has been entered.
Claim Objections
Claim 1 is objected to for the following informalities. Claim 1 uses dashes to visually separate clauses (e.g., “- a region I . . . - a region II”). According to MPEP 608.01(m), a claim must be a single sentence. As the dashes are used visually separating clauses, and do no provide a grammatical function, they are improper. Simply removing the dashes or making the dashes (a) or (b) (e.g., (a) region I . . . (b) region II”) would be ameliorative. Appropriate correction is required.
Withdrawn Objections & Rejections
The objections and rejections presented herein represent the full set of objections and rejections currently pending in the application. Any objections or rejections not specifically reiterated are hereby withdrawn.
The rejection of claims 1-4 and 8-9 under 35 U.S.C. 103 as being unpatentable over Chang et al. (WO2018148445A1, 2018, on IDS 03/22/2023, previously cited) as evidenced by Arora et al. (MABS, 2016, previously cited) and Spaner et al. (EBioMedicine, 2018) is withdrawn due to Applicant’s persuasive arguments as discussed below.
Response to Arguments - persuasive
Applicant argues that the claims further clarify the methods steps of administration to a patient. (Remarks, p6-7). Applicant argues that Chang does not teach the claimed method (Remarks, p7-8). Applicant argues that none of Arora or Spaner cure the claimed deficiencies of Chang (Remarks, p8-9). In regards to the phrase “a substance that is not the antibody”, Applicant argues that the specification is consistent that the substance and the antibody are distinct (Remarks, p9-10).
Applicant’s arguments filed 08/25/2026 are found persuasive. Therefore, the rejection of claims 1-4 and 8-9 under 35 U.S.C. 103 as being unpatentable over Chang et al. (WO2018148445A1, 2018, on IDS 03/22/2023, previously cited) as evidenced by Arora et al. (MABS, 2016, previously cited) and Spaner et al. (EBioMedicine, 2018) is withdrawn.
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.
Written Description
Claims 1-4 and 8-13 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.
Claim 1 is drawn to a method for treating a subject by administering a pharmaceutical composition comprising a NK cell population.
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The pharmaceutical composition and the NK cell population itself is a product-by-process comprising mixing and incubating the NK cell population with a substance and an antibody prior to administration. The mixing step can comprise either (i) first mixing the NK cell population and the substance, and then adding the antibody, or (ii) mixing the antibody and the substance, and then adding the NK cell population. As a result of this binding pattern, the antibody is stabilized to the NK cell (see illustration).
The substance itself is undefined and unlimited other than by its function, and other than the fact that the substance is not the antibody (i.e., it must be a different molecule, e.g., if the antibody is IgG1, then the substance itself cannot be IgG1). Thus, the substance is a broad genus.
Claim 1 does not require region I of the substance bind to any specific NK cell surface, and therefore, many bind to any NK cell surface protein.
Additionally, claim 1 does not require any specific antibody.
Claim 2 identifies that that NK cell surface protein is one of NKp46, etc.
Claim 3 identifies that at least one of the regions I or II is a single chain Fv fragment (scFv).
Claim 4 generically identifies the antibody as an antibody drug for a treatment of cancer or an infectious disease, while claim 10 specifies that the antibody is one of muromonab-CD3, etc.
Claim 8 identifies the substance as a protein, while claim 9 identifies the substance as a fusion protein.
Claim 11 identifies that the subject is in need of a treatment with NK cells.
Claim 12 identifies that the subject is in need of a treatment with NK cells having an antibody stabilized by the substance to the NK cell.
Claim 13 requires an additional step of removing unbound antibodies prior to administration.
Under the written description guidelines (see MPEP 2163) the Examiner is directed to determine whether one skilled in the art would recognize that the Applicant was in possession of the claimed invention as a whole at the time of filing. The following considerations are critical to this determination.
To satisfy the written description requirement, a patent specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention. See, e.g., Moba, B.V. v. Diamond Automation, Inc., 325 F.3d 1306, 1319, 66 USPQ2d 1429, 1438 (Fed. Cir. 2003); Vas-Cath, Inc. v. Mahurkar, 935 F.2d at 1563, 19 USPQ2d at 1116. An original claim may lack written description support when (1) the claim defines the invention in functional language specifying a desired result but the disclosure fails to sufficiently identify how the function is performed or the result is achieved or (2) a broad genus claim is presented but the disclosure only describes a narrow species with no evidence that the genus is contemplated. See Ariad Pharms., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1349-50 (Fed. Cir. 2010) (en banc). The written description requirement is not necessarily met when the claim language appears in ipsis verbis in the specification. “Even if a claim is supported by the specification, the language of the specification, to the extent possible, must describe the claimed invention so that one skilled in the art can recognize what is claimed. The appearance of mere indistinct words in a specification or a claim, even an original claim, does not necessarily satisfy that requirement.” Enzo Biochem, Inc. v. Gen-Probe, Inc., 323 F.3d 956, 968, 63 USPQ2d 1609, 1616 (Fed. Cir. 2002).
Accordingly, to satisfy the written description requirement, the specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention. Vas-Cath, Inc. v. Mahurkar, 935 F.2d 1555, 1562-63, 19 USPQ2d 1111 (Fed. Cir. 1991). See also MPEP 2163.
Actual Reduction to Practice
According to the specification the invention hinges on the characteristics of the substance and its ability to both bind a NK cell receptor and an antibody (which itself binds to CD16), stabilizing this interaction.
According to the specification, region I of the substance may be a binding molecule including CSV, B7-H6, MICA, MICB, ULBP1 to 6, IL-15, IL-2, IL-15, IL-2, HLA-F, HLA-B, HLA-E, AICL, KACL, MLL5, PCNA, HLA-B27 dimer, soluble HLA CD112, CD155, and CD48 (paragraph [0038]).
Region I may also be peptide containing a region that can bind to the aforementioned binding proteins (paragraph [0041]).
Alternatively, region I may be an antibody or antigen-binding fragment of antibody that can bind to any NK surface protein, including single chain Fv fragment (scFv), dimeric scFv (di-scFv), diabody, triabody, tetrabody, Fab, F(ab′)2, Fv F(ab′)2, or Fv (paragraph [0039]).
Region II may be any protein molecule that can bind to the antibody and does not inhibit the antibody from binding to CD16, including Protein A, Protein G, etc. (paragraph [0043]); an antibody or an antigen-binding fragment of an antibody (paragraph [0044]); a cross-linking agent (paragraph [0045]); and an aptamer or any low molecular weight compound that can recognize the Fc region of an antibody (paragraph [0050]).
While the specification broadly asserts that the substance may be any combination of the aforementioned components, the specification only demonstrates a single embodiment wherein the substance comprises an anti-human NKp46 scFv (region I) and the sequences 373-297aa of the protein G sequence (region II) (Example 1, paragraph [0119]), referred to as a pG2-NKp46 substance (paragraph [0122]).
According to Examples 2 and 3, incubating the purified pG2-NKp46 substance with antibody drugs resulted in the anchoring of those drugs on the surface of GAIA -102 cells (paragraphs [0122-0126]). It is noted that GAIA -102 cells are a well-known line of NK-like cells.
As discussed above, the specification does not demonstrate any other embodiment of the substance.
Additionally, the specification does not demonstrate specific steps of treating a subject with the antibodies.
Therefore, the Applicant has not demonstrated a reduction to practice of the use of any substance comprising a region I that can bind to a surface protein of the NK cell and a region II that can bind to the antibody as claimed.
While the specification asserts myriad combinations of compounds that may comprise regions I and II of the substance, the specification only demonstrates reduction to practice of a single substance which is a pG2-NKp46 fusion protein. No other substances are made or tested.
Additionally, the specification only demonstrates tethering of the pG2-NKp46 substance to therapeutic antibodies to NK cells, not antibodies generically, and in no case demonstrates administering NK cells to subjects.
State of the Art and Quantity of Experimentation
According to MPEP 2163(II)(2), while information which is well known in the art need not be described in detail in the specification (See, e.g., Hybritech, Inc. v. Monoclonal Antibodies, Inc., 802 F.2d 1367, 1379-80, 231 USPQ 81, 90 (Fed. Cir. 1986)), there is an inverse correlation between the level of skill and knowledge in the art and the specificity of disclosure necessary to satisfy the written description requirement and sufficient information must be provided to show that the inventor had possession of the invention as claimed.
However, the method of making the claimed invention is not well established. Specifically, the art is completely silent as to any substance that simultaneously binds to both an antibody that binds to CD16 receptor on a NK cell and an NK cell surface receptor, wherein the substance is not the antibody.
The closet prior art is Chang et al. (WO2018148445A1, on IDS 03/22/2023, previously cited), who discloses a multi-region fusion protein comprising a first antigen binding site that binds to NKG2D (a NK cell surface protein), a second antigen-binding site that binds to a tumor antigen, and a third site comprising an antibody Fc domain or portion thereof that binds to CD16 (claim 1). Therefore, while Chang discloses linking an NK cell surface protein with CD16, the protein of Chang does not bind an antibody specially.
Sentman et al. (US20120294857A1) discloses a bi-specific fusion protein comprising an antibody fragment operably linked to a NK cell receptor (claim 1). The antibody fragment binds to CD16 on the surface of an NK cell (claim 3). However, this protein is distinguishable from the instant invention because the instant substance binds to an antibody that then binds to CD16 and is not a fusion protein comprising an antibody fragment that binds to CD16 as in Sentman.
Shin et al. (JP2009500346, on IDS 03/22/2023) discloses a fusion molecule that binds to a NK cell surface receptor (claims 1 and 6) comprising a tumor antigen binding domain and an immune cell binding domain (claim 1), but not a domain that binds to any antibody.
Therefore, the art does not provide adequate guidance on how to make and perform the method regarding the use of any substance that may bind to an antibody and a NK cell receptor as claimed. Thus, making and performing the invention is not well established.
As a result, it appears that the claimed functional outcome (i.e., stabilizing an antibody that binds to a CD16 surface receptor with a substance that also binds to a NK cell surface protein) requires the specific pG2-NKp46 fusion protein described in the specification.
Conclusion
The Examiner concludes that a person of ordinary skill in the art would find that the specification inadequately describes the claimed invention that uses any of the broad genus of a substance comprising a region I and region II that binds to a NK cell surface protein and an antibody (that itself binds to CD16 on the NK cell). The written description would not have led a person of ordinary skill in the art to understand the inventor possessed the entire scope of the claimed invention. Ariad, 598 F.3d at 1353–54 ('[T]he purpose of the written description requirement is to ensure that the scope of the right to exclude, as set forth in the claims, does not overreach the scope of the inventor's contribution to the field of art as described in the patent specification.' (internal quotation marks omitted).").
According to MPEP 2163(II)(2), while information which is well known in the art need not be described in detail in the specification (See, e.g., Hybritech, Inc. v. Monoclonal Antibodies, Inc., 802 F.2d 1367, 1379-80, 231 USPQ 81, 90 (Fed. Cir. 1986)), there is an inverse correlation between the level of skill and knowledge in the art and the specificity of disclosure necessary to satisfy the written description requirement and sufficient information must be provided to show that the inventor had possession of the invention as claimed.
As discussed above, the specification broadly lists possible combinations of components to form substances, but only reduces to practice a single pG2-NKp46 fusion protein. However, as discussed above, the art is completely silent as to substances with the claimed properties, let alone, substances with those properties which are also effective for stabilizing antibodies (whether therapeutic or otherwise) to the CD16 receptor on an NK cell. Moreover, the disclosure only demonstrates a single reduction to practice of a substance that is a pG2-NKp46 fusion protein.
Furthermore, disclosure of an antigen fully characterized by its structure, formula, chemical name, physical properties, or deposit in a public depository does not, without more, provide an adequate written description of an antibody claimed by its binding affinity to that antigen, even when preparation of such an antibody is routine and conventional. See Amgen Inc. v. Sanofi, 872 F.3d 1367, 1378, 124 USPQ2d 1354, 1361 (Fed. Cir. 2017)(“knowledge of the chemical structure of an antigen [does not give] the required kind of structure-identifying information about the corresponding antibodies”); see also Centocor Ortho Biotech, Inc. v. Abbott Labs., 636 F.3d 1341, 1351-52, 97 USPQ2d 1870, 1877 (Fed. Cir. 2011)(patent disclosed the antigen the claimed antibody was supposed to bind, but did not disclose any antibodies with the specific claimed properties).
In the instant case, while the disclosure describes possible binding arrangements of the various possible components of region I or region II (e.g., region I may also be an antibody or antigen-binding fragment of antibody that can bind to any of the NK cell surface proteins described (paragraph [0039]). And conversely, region II may be any of various protein molecules that can bind to an antibody and do not inhibit the binding of the antibody to CD16 (FcγRIII) on NK cells (paragraph [0043]).
Additionally, the written description requirement requires that there is a sufficient description of representative number of species by actual reduction to practice.
According to MPEP 2163, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus. See AbbVie Deutschland GmbH & Co., KG v. Janssen Biotech, Inc., 759 F.3d 1285, 1300, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014) (Claims directed to a functionally defined genus of antibodies were not supported by a disclosure that “only describe[d] one type of structurally similar antibodies” that “are not representative of the full variety or scope of the genus.”). The disclosure of only one species encompassed within a genus adequately describes a claim directed to that genus only if the disclosure “indicates that the patentee has invented species sufficient to constitute the gen[us].” See Enzo Biochem, 323 F.3d at 966, 63 USPQ2d at 1615; Noelle v. Lederman, 355 F.3d 1343, 1350, 69 USPQ2d 1508, 1514 (Fed. Cir. 2004) (Fed. Cir. 2004) (“[A] patentee of a biotechnological invention cannot necessarily claim a genus after only describing a limited number of species because there may be unpredictability in the results obtained from species other than those specifically enumerated.”).
As discussed above, the specification describes myriad and disparate combinations of molecules including binding molecule, peptides that can themselves bind to binding molecules, antibodies or antigen-binding fragments, any protein that can bind to an antibody that does not inhibit binding to CD16, a cross-linking agent, or an aptamer, there is only single reduction to practice of a substance that is a pG2-NKp46 fusion protein.
However, for inventions in an unpredictable art, adequate written description of a genus which embraces widely variant species cannot be achieved by disclosing only one species within the genus. See, e.g., Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406.
See also, AbbVie, 759 F.3d at 1300-01, 111 USPQ2d 1780, 1790-91 (Fed. Cir. 2014) (Holding that claims to all human antibodies that bind IL-12 with a particular binding affinity rate constant (i.e., koff) were not adequately supported by a specification describing only a single type of human antibody having the claimed features because the disclosed antibody was not representative of other types of antibodies in the claimed genus, as demonstrated by the fact that other disclosed antibodies had different types of heavy and light chains, and shared only a 50% sequence similarity in their variable regions with the disclosed antibodies).
Therefore, again, it is concluded that the there is insufficient written description of the instantly claimed method that uses any substance that binds to both bind a NK cell receptor and an antibody (which itself binds to CD16), stabilizing this interaction, and the written description would not have led a person of ordinary skill in the art to understand that the inventor possessed the entire scope of the claimed invention.
Scope of Enablement
Claims 1-4 and 8-13 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for:
A method for treating a subject, which uses a substance . . . the substance having: a region I . . . and a region II . . . wherein the region I comprises an NKp46 small chain variable fragment (scFv) and wherein the region II comprises Protein G comprising amino acid sequences 373-297
does not reasonably provide enablement for:
A method for treating a subject, which uses a substance . . . the substance having: a region I . . . and a region II (which are any regions)
The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to practice the invention commensurate in scope with these claims.
SCOPE OF THE INVENTION
The breadth of the claims encompasses a method for treating a subject that uses a substance.
Regarding claim 1, the active method steps require mixing and incubating a substance, an antibody, and a population of NK cells and then administering to a patient a pharmaceutical composition comprising the substance, NK cells, and antibody.
The substance comprises a region I that can bind to a surface protein of the NK cell and a region II that can bind to the antibody. As a result of the mixing step, the antibody binds to CD16 on the surface of an NK cell, region II of the substance binds to the antibody, and region I of the substance binds to a surface protein on the NK cell (see illustration).
Claim 1 requires that the substance not be the antibody (i.e., it must be a different molecule, e.g., if the antibody is IgG1, then the substance itself cannot be IgG1). However, the substance is unlimited otherwise. Therefore, the claim is a broad genus of any substance as long as it comprises a region I that binds to a NK cell surface protein, a region II that binds to an antibody, and is itself not the same type of molecule as the antibody.
The antibody must bind to region II of the substance and CD16 on a NK cell, but is otherwise unlimited.
The surface protein on the NK cell must bind to region I of the substance but it otherwise unlimited.
Claim 2 identifies that that NK cell surface protein is one of NKp46, etc.
Claim 3 identifies that at least one of the regions I or II is a single chain Fv fragment (scFv).
Claim 4 generically identifies the antibody as an antibody drug for a treatment of cancer or an infectious disease, while claim 10 specifies that the antibody is one of muromonab-CD3, etc.
Claim 8 identifies the substance as a protein, while claim 9 identifies the substance as a fusion protein.
Claim 11 identifies that the subject is in need of a treatment with NK cells.
Claim 12 identifies that the subject is in need of a treatment with NK cells having an antibody stabilized by the substance to the NK cell.
Claim 13 requires an additional step of removing unbound antibodies prior to administration.
As discussed supra, the specification fails to describe a method of using a broad genus of any substance comprising regions I or II as described above and would require undue experimentation to discover species of substances capable of binding to any NK cell surface protein and an antibody to CD16 on a NK cell and used for administration to a subject as claimed.
Instead, the specification only discloses and provides guidance for the claimed method of treating a subject when the substance region I comprises an anti-human NKp46 small chain variable fragment (scFv) and region II comprises the sequences 373-297aa of the protein G sequence.
The factors to be considered in determining whether undue experimentation is required are summarized In re Wands 858 F.2d 731, 8 USPQ2nd 1400 (Fed. Cir, 1988). The Court in Wands states: “Enablement is not precluded by the necessity for some 'experimentation.'” Clearly, enablement of a claimed invention cannot be predicated on the basis of quantity of experimentation required to make or use the invention. “Whether undue experimentation is needed is not a single simple factual determination, but rather is a conclusion reached by weighing many factual considerations.” (Wands, 8 USPQ2d 1404). The factors to be considered in determining whether undue experimentation is required include: (1) the quantity of experimentation necessary, (2) the amount or direction or guidance presented, (3) the presence or absence of working examples, (4) the nature of the invention, (5) the state of the prior art, (6) the relative skill of those in the art, (7) the predictability or unpredictability of the art, and (8) the breadth of the claims. While all of these factors are considered, a sufficient amount for a prima facie case is discussed below.
The office has analyzed the specification in direct accordance to the factors outlined in In re Wands. MPEP 2164.04 states: "[W]hile the analysis and conclusion of a lack of enablement are based on factors discussed in MPEP 2164.01(a) and the evidence as whole, it is not necessary to discuss each factor in written enablement rejection." These factors will be analyzed, in turn, to demonstrate that one of ordinary skill in the art would have had to perform "undue experimentation" to make and/or use the invention and therefore, Applicant's claims are not enabled commensurate with the scope of the invention.
ACTUAL REDUCTION TO PRACTICE
According to the specification, region I of the substance may be a binding molecule including CSV, B7-H6, MICA, MICB, ULBP1 to 6, IL-15, IL-2, IL-15, IL-2, HLA-F, HLA-B, HLA-E, AICL, KACL, MLL5, PCNA, HLA-B27 dimer, soluble HLA CD112, CD155, and CD48 (paragraph [0038]).
Region I may also be peptide containing a region that can bind to the aforementioned binding proteins (paragraph [0041]).
Alternatively, region I may be an antibody or antigen-binding fragment of antibody that can bind to any NK surface protein, including single chain Fv fragment (scFv), dimeric scFv (di-scFv), diabody, triabody, tetrabody, Fab, F(ab′)2, Fv F(ab′)2, or Fv (paragraph [0039]).
Region II may be any protein molecule that can bind to the antibody and does not inhibit the antibody from binding to CD16, including Protein A, Protein G, etc. (paragraph [0043]); an antibody or an antigen-binding fragment of an antibody (paragraph [0044]); a cross-linking agent (paragraph [0045]); and an aptamer or any low molecular weight compound that can recognize the Fc region of an antibody (paragraph [0050]).
While the specification broadly asserts that the substance may be any combination of the aforementioned components, the specification only demonstrates a single embodiment wherein the substance comprises an NKp46 scFv (region I) and the sequences 373-297aa of the protein G sequence (region II) (Example 1, paragraph [0119]), referred to as a pG2-NKp46 substance (paragraph [0122]).
According to Examples 2 and 3, incubating the purified pG2-NKp46 substance with antibody drugs resulted in the anchoring of those drugs on the surface of GAIA -102 cells (paragraphs [0122-0126]). It is noted that GAIA -102 cells are a well-known line of NK-like cells.
As discussed above, the specification does not demonstrate any other embodiment of the substance.
Additionally, the specification does not demonstrate specific steps of treating a subject with the antibodies.
The absence of working examples directed to the broad genus of substances comprising regions I and II as claimed necessitates further experimentation.
Therefore, the specification does not provide sufficient guidance on how to make and use the broad genus of any substance with regions I and II as claimed.
Regarding dependent claim 2, the claim broadly claims that the substance can binds to any of NKp46, etc., but the specification only demonstrates binding to NKp46 specifically (paragraph [0026]; Fig. 6).
Regarding dependent claim 3, the claim identifies that either region I or region II is a scFV. However, the specification only demonstrates a region I NKp46-binding scFV (paragraph [0026]; Fig. 6). The specification does not demonstrate a region II (antibody binding region) comprising a scFV, but rather only a region comprising sequences 373-297aa of the protein G sequence
STATE OF THE ART & QUANTITY OF EXPERIMENTATION
The art is completely silent as to the claimed method.
The closet prior art is Chang et al. (WO2018148445A1, on IDS 03/22/2023, previously cited), who discloses a multi-region fusion protein comprising a first antigen binding site that binds to NKG2D (a NK cell surface protein), a second antigen-binding site that binds to a tumor antigen, and a third site comprising an antibody Fc domain or portion thereof that binds to CD16 (claim 1). Therefore, while Chang discloses linking an NK cell surface protein with CD16, the protein of Chang does not bind an antibody specially.
Sentman et al. (US20120294857A1) discloses a bi-specific fusion protein comprising an antibody fragment operably linked to a NK cell receptor (claim 1). The antibody fragment binds to CD16 on the surface of an NK cell (claim 3). However, this protein is distinguishable from the instant invention because the instant substance binds to an antibody that then binds to CD16 and is not a fusion protein comprising an antibody fragment that binds to CD16 as in Sentman.
Shin et al. (JP2009500346, on IDS 03/22/2023) discloses a fusion molecule that binds to a NK cell surface receptor (claims 1 and 6) comprising a tumor antigen binding domain and an immune cell binding domain (claim 1), but not a domain that binds to any antibody.
Therefore, because the prior art is silent as to the claimed substance or the use of the substance, let alone the use of the substance in a method for stabilizing antibodies, binding to any surface protein, and treating a subject, there is ample reason to conclude that there would be a high degree of unpredictability in a mammalian embodiment of the instant invention.
As a result, since the prior and art at the effective filing date of the present application did not provide guidance for the genus of any substance comprising regions I and II as claimed, the physiological art is recognized as unpredictable (MPEP 2164.03). As set forth in In re Fisher, 166 USPQ 18 (CCPA 1970), compliance with 35 USC 112, first paragraph requires: “That scope of claims must bear a reasonable correlation to scope of enablement provided by specification to persons of ordinary skill in the art; in cases involving predictable factors, such as mechanical or electrical elements, a single embodiment provides broad enablement in the sense that, once imagined, other embodiments can be made without difficulty and their performance characteristics predicted by resort to known scientific laws; in cases involving unpredictable factors, such as most chemical reactions and physiological activity, scope of enablement varies inversely with degree of unpredictability of factors involved.” Moreover, the courts have also stated that reasonable correlation must exist between scope of exclusive right to patent application and scope of enablement set forth in the patent application (27 USPQ2d 1662 Ex parte Maizel). In view of the foregoing, due to the lack of sufficient guidance provided by the specification regarding the issues set forth above, the state of the relevant art, and the breadth of the claims, it would have required undue experimentation for one skilled in the art to make and use the instant broadly claimed invention.
CONCLUSION
In conclusion, since the art is silent as to substances comprising regions I and II as claimed and is highly unpredictable with respect to using any substance to stabilize an antibody and being used for administration to a patent, and since the specification does not provide ample guidance with respect to achieving the unexpected results (of the method using any substance), one would be burdened with undue experimentation to make or use the claimed invention of any substance comprising regions I and II as claimed to stabilize an antibody, bind to any NK cell surface protein, and be used for administration to a subject.
Thus, given the breadth of the claims and the limited scope of the specification, an undue quantity of experimentation is required to make and use the invention beyond the scope of a method of using a substance for administrating to a patient wherein the region I comprises an NKp46 small chain variable fragment (scFv) and wherein the region II comprises Protein G comprising amino acid sequences 373-297 as identified above.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JOSEPH (PAUL) MIANO whose telephone number is (571)272-0341. The examiner can normally be reached Mon-Fri from 8:30am to 5:30pm.
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/JOSEPH PAUL MIANO/Examiner, Art Unit 1631
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