DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claims 2, 7-13, 17, 19-29 and 33 are pending
Election/Restrictions
Applicant’s election without traverse of and psoriasis antibody comprising a HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 9, a HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 10, a HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 11, a LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 12, a LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 13, and a LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 14 in the reply filed June 9, 2026 is acknowledged.
Claims 2, 7-13, 17, 19-29, and 33 are under examination.
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code in paragraph 59. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
Claim Rejections - 35 USC § 112
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.
Claims 2, 7-13, 17, 19-29, and 33 are rejected on the basis that it contains an improper Markush grouping of alternatives. See In re Harnisch, 631 F.2d 716, 721-22 (CCPA 1980) and Ex parte Hozumi, 3 USPQ2d 1059, 1060 (Bd. Pat. App. & Int. 1984). A Markush grouping is proper if the alternatives defined by the Markush group (i.e., alternatives from which a selection is to be made in the context of a combination or process, or alternative chemical compounds as a whole) share a “single structural similarity” and a common use. A Markush grouping meets these requirements in two situations. First, a Markush grouping is proper if the alternatives are all members of the same recognized physical or chemical class or the same art-recognized class, and are disclosed in the specification or known in the art to be functionally equivalent and have a common use. Second, where a Markush grouping describes alternative chemical compounds, whether by words or chemical formulas, and the alternatives do not belong to a recognized class as set forth above, the members of the Markush grouping may be considered to share a “single structural similarity” and common use where the alternatives share both a substantial structural feature and a common use that flows from the substantial structural feature. See MPEP § 2117.
The Markush grouping of the species of antibodies is improper because the alternatives defined by the Markush grouping do not share both a single structural similarity and a common use for the following reasons: As disclosed below, the claimed anti-VIASTA antibodies have distinct CDR amino acid sequences. In addition, the specification discloses that FIG. 16 show that 16A1, 17E9 and 20E4 compete for the same epitope on VISTA, while 1E8, 9F9, and 15D11 bind to different epitopes (paragraph 333). Thus, the claimed anti-VISTA antibodies have distinct amino acid sequences and bind distinct epitopes on VISTA.
To overcome this rejection, Applicant may set forth each alternative (or grouping of patentably indistinct alternatives) within an improper Markush grouping in a series of independent or dependent claims and/or present convincing arguments that the group members recited in the alternative within a single claim in fact share a single structural similarity as well as a common use.
SEQ ID Nos: 1-2-3
Gly Tyr Trp Met Gln Ala Ile Tyr Pro Gly Asp Gly Asp Thr Arg Tyr Ser Gln Lys Phe Lys
Arg Asp Tyr Gly Ala Trp Phe Ala Tyr
SEQ ID Nos: 17-18-19
Ser Ser Trp Ile Glu Glu Ile Phe Pro Gly Ser Gly Ser Leu Asn Phe Asn Glu Lys Phe Lys Gly Arg Pro Pro Gly Trp Phe Phe Asp Val
SEQ ID Nos: 33-34-35
Asp Thr Phe Ile His Arg Ile Asp Pro Ala Asn Gly Asn Ser Lys Tyr Asp Pro Lys Phe Gln Gly Trp Pro Ser Asn Trp Glu Ala Met Asp Tyr
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.
Claims 26-28 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 method of treating an auto-immune disease, inflammation, an infection and graft versus host disease (GvHD) in an individual, comprising administering to the individual an effective amount of the anti-VISTA construct does not reasonably provide enablement for method of treating a disease or condition in an individual, comprising administering to the individual an effective amount of the anti-VISTA construct. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
Claim 26 is drawn to method of treating a disease or condition in an individual,
comprising administering to the individual an effective amount of the anti-VISTA construct of claim 2.
The specification disclose that anti-VISTA antibodies suppressed T cell proliferation (Example 15). The specification disclose that MRL-lpr mice did not develop lupus if treated with anti-VISTA antibodies (Example 16). The specification discloses that treatment with anti-VISTA reduces levels of anti-nuclear antibodies and levels of IFNα (Id). The specification disclose that anti-VISTA antibodies mitigated Graft vs Host Disease (GVHD) (Example 17).
ElTanbouly et al (Science 367(6475) 1-36, 2019) disclose that VISTA is a member of the B7 family that is distinct from other negative checkpoint molecules in that it is constitutively expressed on naïve T cells (page 2, 3rd paragraph). ElTanbouly disclose that mice deficient in VISTA show an enhanced frequency of antigen-experienced memory CD4+ CD44hi T cells, heightened cytokine production, and an increased propensity to develop autoimmunity (Id). ). ElTanbouly disclose that VISTA knockout mice exhibited GVHD characteristics while anti-hVISTA antibodies induces GVHD (Fig 4; pages 34 and 35). ElTanbouly et al (Front Immunol 11: (595950) February 2021) discloses that agonist anti-VISTA antibodies suppress GVHD and that VISTA appeared to play a role in several diseases including rheumatoid arthritis, psoriasis, transplant rejection and acute hepatitis (page 3, 1st column, 3rd paragraph to page 3, 2nd column, 1st paragraph). Molloy et al (WO 2017/181139, published October 2017, IDS) disclose that agonist anti-VISTA antibodies may be used for treating and preventing lupus, GVHD, RA, IBD, chronic infection and hepatotoxicity, psoriasis and for
Preventing acute and chronic autoimmune, allergic, inflammatory conditions (paragraphs 771-775 Examples 16-40). Han et al (Science Transl Med 11 (eaax1159) 1-14, 2019) discloses treatment with agonist anti-VISTA antibodies suppresses lupus in MRL/lpr mice (page 5, 2nd column, 2nd paragraph to page 7, 2nd column, 2nd paragraph; Figure 6). Thus, the art disclose that agonis anti-VISTA antibodies are capable of treating auto-immune disease, inflammation, GvHD, lupus and transplant rejection but not any disease or condition in an individual including an infection, cancer or any condition associated with a transplant).
One cannot extrapolate the teaching of the specification to the enablement of the claims because the specification does not provide examples or guidance for treating any disease with an agonist anti-VISTA antibody. The specification and the art disclose that agonis anti-VISTA antibodies are capable of treating auto-immune disease, inflammation, arthritis, asthma, GvHD, lupus and transplant rejection but not any disease or condition in an individual. There are no examples or art demonstrating that agonist anti-VISTA antibodies are capable of treating an infection, cancer or any condition associated with a transplant. The mechanisms for downregulating an immune response in a treatment for autoimmune disease arthritis, asthma, GvHD or lupus would be distinct from the mechanisms involved in treating a proliferative disease such as cancer. The specification does not provide a nexus between administering an anti-VISTA antibody and the treatment of any disease or condition besides auto-immune disease, inflammation, arthritis, asthma, GvHD, lupus and transplant rejection.
MPEP 2164.03 states that
The amount of guidance or direction needed to enable the invention is inversely related to the amount of knowledge in the state of the art as well as the predictability in the art. In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970). The “amount of guidance or direction” refers to that information in the application, as originally filed, that teaches exactly how to make or use the invention.
MPEP 2164.03 further states that
The “predictability or lack thereof” in the art refers to the ability of one skilled in the art toextrapolate the disclosed or known results to the claimed invention. If one skilled in the art can readily anticipate the effect of a change within the subject matter to which the claimed invention pertains, then there is predictability in the art. On the other hand, if one skilled in the art cannot readily anticipate the effect of a change within the subject matter to which that claimed invention pertains, then there is lack of predictability in the art. Accordingly, what is known in the art provides evidence as to the question of predictability. …
The scope of the required enablement varies inversely with the degree of predictability involved, but even in unpredictable arts, a disclosure of every operable species is not required. A single embodiment may provide broad enablement in cases involving predictable factors, such as mechanical or electrical elements. In re Vickers, 141 F.2d 522, 526-27, 61 USPQ 122, 127 (CCPA 1944); In re Cook, 439 F.2d 730, 734, 169 USPQ 298, 301 (CCPA 1971). However, in applications directed to inventions in arts where the results are unpredictable, the disclosure of a single species usually does not provide an adequate basis to support generic claims. In re Soll, 97 F.2d 623, 624, 38 USPQ 189, 191 (CCPA 1938). In cases involving unpredictable factors, such as most chemical reactions and physiological activity, more may be required. In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970) (contrasting mechanical and electrical elements with chemical reactions and physiological activity). See also In re Wright, 999 F.2d 1557, 1562, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993); In re Vaeck, 947 F.2d 488, 496, 20 USPQ2d 1438, 1445 (Fed. Cir. 1991). This is because it is not obvious from the disclosure of one species, what other species will work.
MPEP 2164.08(b) states that
The presence of inoperative embodiments within the scope of a claim does not necessarily render a claim nonenabled. The standard is whether a skilled person could determine which embodiments that were conceived, but not yet made, would be inoperative or operative with expenditure of no more effort than is normally required in the art. Atlas Powder Co. v. E.I. du Pont de Nemours & Co., 750 F.2d 1569, 1577, 224 USPQ 409, 414 (Fed. Cir. 1984) (prophetic examples do not make the disclosure nonenabling).
Although, typically, inoperative embodiments are excluded by language in a claim (e.g., preamble), the scope of the claim may still not be enabled where undue experimentation is involved in determining those embodiments that are operable. A disclosure of a large number of operable embodiments and the identification of a single inoperative embodiment did not render a claim broader than the enabled scope because undue experimentation was not involved in determining those embodiments that were operable. In re Angstadt, 537 F.2d 498, 502-503, 190 USPQ 214, 218 (CCPA 1976). However, claims reading on significant numbers of inoperative embodiments would render claims nonenabled when the specification does not clearly identify the operative embodiments and undue experimentation is involved in determining those that are operative.
Given the disclosure of the specification and the teaching in the art that indicates that agonist anti-VISTA antibodies are capable of treating auto-immune disease, inflammation, arthritis, asthma, GvHD, lupus and transplant rejection but not any disease or condition in an individual with a MIC polypeptide binding agent, given that treating a proliferative disease and an infection would require the activation of T cells, not the inhibition of T cell function and the unpredictability of treating a proliferative disease, one could not predictably treat any disease with the claimed agonistic anti-VISTA antibodies.
Therefore, in view of the breadth of the claims, lack of guidance in the specification, the absence of working examples, and the state of the art, it would require undue experimentation for one skilled in the art to practice the invention as broadly claimed.
An anti-VISTA antibody comprising: a VH CDR1 comprising the amino acid sequence of SEQ ID NO: 9; a VH CDR2 comprising the amino acid sequence of SEQ ID NO: 10; a VH CDR3 comprising the amino acid sequence of SEQ ID NO: 11; a VL CDR1 comprising the amino acid sequence of SEQ ID NO: 12; a VL CDR2 comprising the amino acid sequence of SEQ ID NO: 13; and a VL CDR3 comprising the amino acid sequence of SEQ ID NO: 14, an anti-VISTA antibody comprising: a VH CDR1 comprising the amino acid sequence of SEQ ID NO: 17; a VH CDR2 comprising the amino acid sequence of SEQ ID NO: 18; a VH CDR3 comprising the amino acid sequence of SEQ ID NO: 19; a VL CDR1 comprising the amino acid sequence of SEQ ID NO: 20; a VL CDR2 comprising the amino acid sequence of SEQ ID NO: 21; and a VL CDR3 comprising the amino acid sequence of SEQ ID NO: 22 and an anti-VISTA antibody comprising: a VH CDR1 comprising the amino acid sequence of SEQ ID NO: 25; a VH CDR2 comprising the amino acid sequence of SEQ ID NO: 26; a VH CDR3 comprising the amino acid sequence of SEQ ID NO: 27; a VL CDR1 comprising the amino acid sequence of SEQ ID NO: 28; a VL CDR2 comprising the amino acid sequence of SEQ ID NO: 29; and a VL CDR3 comprising the amino acid sequence of SEQ ID NO: 30 are free of the art.
Summary
No claims allowed.
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/MARK HALVORSON/ Primary Examiner, Art Unit 1646
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