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 .
Claims 1-3, 5, and 12-45 are pending and under consideration.
Priority
The instant application is a DIV of 16/825,955, now US Pat. No. 11,964,016.
Information Disclosure Statement
The Information Disclosure Statements (IDSs) filed on 6/26/2024, 11/25/2024 and 2/13/2025 (2) have been considered.
Claim Objections
Claims 37 and 39 are objected to because of the following informalities:
In claim 37, lines 2 and , replace the term “with” with the term “within”
In claim 39, lines 3 and 5, replace the term “with” with the term “within”
Appropriate correction is required.
Claim Rejections - 35 USC § 112
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.
Claims 1-3, 5, 12-25 and 43-45 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 of treating reducing or eliminating allergen-specific serum IgE in a subject; or for treating allergy or reducing the severity of an allergic reaction to an allergen; comprising administering to a subject in need thereof a therapeutically effective amount of an IL-4/IL-13 pathway inhibitor and the anti-BCMA/anti-CD3 bispecific antibody that comprises the heavy and light sequences recited in instant claims 36-42, does not reasonably provide enablement for a method of reducing or eliminating allergen-specific serum IgE in a subject or a method of preventing severity of an allergic reaction; comprising administering to a subject in need thereof a therapeutically effective amount of an IL- 4/IL-13 pathway inhibitor and a plasma cell ablating agent. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention commensurate in scope with these claims.
In in re Wands, 8USPQ2d, 1400 (CAFC 1988) page 1404, the factors to be considered in determining whether a disclosure would require undue experimentation include: (1) Nature of the invention, (2) the state of the prior art, (3) the predictability or lack thereof in the art, (4) the amount of direction or guidance present, (5) the presence or absence of working examples, (6) the breath of the claims, (7) the quantity of experimentation needed, (8) relative skill of those in the art.
The instant disclosure fails to meet the enablement requirement for the following reasons:
The instant claims encompass a method of reducing or eliminating allergen-
specific serum IgE in a subject or a method of preventing severity of an allergic reaction; comprising administering to a subject in need thereof a therapeutically effective amount
of an IL-4/IL-13 pathway inhibitor and a plasma cell ablating agent. Thus, the claims
encompass administering "plasma cell ablating agent" for preventing, reducing or eliminating an allergic reaction.
The state of the prior art and the predictability or lack thereof in the art:
The relevant art teaches that inhibition of the IL-4/IL-13 receptor system
completely abrogates humoral immune response to allergen and development of
allergic symptoms in vivo, (IDS, Grunewald, the Journal of Immunology, 1998, Vo: 160,
No: 8, pages 4004-4009. Especially see abstract and page 4008, column 1). Numerous
IL-4/IL-13 pathway inhibitors, (small molecules, siRNA, peptides, antibodies) are known
in the art. For example, pitrakinra is (a dual IL-4/IL-13 antagonist) is a recombinant
human IL-4 variant, AS1517499, (small molecule,) is a potent STAT6; IL-4- and IL-13-
mediated signaling asthma. However, the relevant art does not establish a link between
anti-BCMA X anti-CD3 antibodies and allergy of IgE serum levels. At the time of filing, anti-BCMA/anti-CD3 antibodies were known in the art. For example, Caraccio et al, (IDS, Frontiers in Immunology, April 2020, Vol. 11, Article 501, pages 1-25)
teaches numerous anti-BCMA/CD3 that are in clinical trials for the treatment of multiple
myeloma, (see tables 1 and 2). The reference teaches that the bispecific antibodies are
designed differently and have different structures, (see figure 2 and table 3). However,
neither the relevant art nor the instant specification establishes a link between "all
plasma cell abating agents" and allergy or IgE serum levels. The specification only
teaches one anti-BCMA/anti-CD3, which comprises the heavy and light sequences
recited in claims 37-38, 41-42 is used in in-vitro and in-vivo studies. The specification
teaches that combination therapy of an IL-4/IL-13 pathway inhibitors with REGN5459,
(anti-BCMA X anti-CD3; having the heavy and light sequences recited in claims 37-38,
41-42) eliminated serum house dust mite, (HDM) specific IgE in a chronic HDM model,
(see figure 4). However, a large quantity of experimentation would be required of the
skilled artisan to determine if all plasma cell ablating agents (in combination with an IL-
4/IL-13 pathway inhibitor) reduce/eliminate allergen-specific serum IgE; treat allergy; or
prevent/reduce severity of an allergic reaction to an allergen. Such experimentation is
considered undue. With respect claims 2-3, which encompass preventing the severity of an allergic reaction to an allergen, or preventing the generation of new IgE+ plasma
cells, undue experimentation would be required of the skilled artisan to determine the
quantity of IL-4/IL-13 inhibitor and a plasma cell ablating agent to be administered, the
best route of administration, and the duration of treatment, to "prevent" the severity of
an allergic reaction to an allergen, or prevent generation of new IgE+ plasma cells. In the instant case, one skilled in the art would not be able to predict that the disparate "plasma cell ablating agents" would be effective in reducing serum IgE or treat allergy or reducing the severity of an allergic reaction to an allergen.
The amount of direction and guidance present and the presence or absence of working examples: The specification teaches that "plasma cell ablating agent" is selected from the group consisting of a B-cell maturation antigen (BCMA) targeting agent, a proteasome inhibitor, a histone deacetylase inhibitor, a B-cell activating factor (BAFF) inhibitor, and an inhibitor of A proliferation inducing ligand (APRIL; CD256). In one embodiment, the BCMA targeting agent is selected from the group consisting of an anti-BCMA/anti-CD3 bispecific antibody, a chimeric antigen receptor against BCMA, and an anti-BCMA antibody conjugated to a cytotoxic drug, [paragraph 014]. However, the members of this markush group do not share a substantial structural feature and/or a common use for the following reasons: for example B-cell-activating factor (BAFF) is a member of the tumor-necrosis factor (TNF) family and is a survival factor for B cells that controls B-cell maturation; B-cell maturation antigen (BCMA) is a target for multiple myeloma therapies; proteasome inhibitors are an important class of drugs for the treatment of multiple myeloma and mantle cell lymphoma; and histone deacetylase (HDAC) inhibitors are a relatively new class of anti-cancer agents that play important roles in epigenetic or non-epigenetic regulation. Only the specification establishes a link
between anti-BCMA X anti-CD3 and IgE serum levels. Moreover, one skilled in the art
would not be able to predict that all the agents encompassed by "plasma cell ablating agent” would have been the same function, especially in conjunction with an IL-4/IL-13 pathway inhibitor.
The specification teaches that the anti-BCMA X anti-CD3, (REGN5459),
(comprising the HCVR of SEQ ID NO:12 and LCVR of SEQ ID NO: 20, see paragraph
0136) treatment alone transiently reduced IgE production, but serum IgE levels were
restored after 6 weeks of rest (Figures 2A & 2B; Table 2). The specification teaches that
combination of anti-IL-4Ra with anti-BCMA/anti-CD3 treatment eliminated serum IgE
(undetectable by IgE ELISA), demonstrating the efficacy of blocking IL-4Ra and
depleting plasma cells with anti-BCMA/anti-CD3 as a successful strategy to block IgE
production, (see figures 2A & 2B; Table 2).
The breadth of the claims and the quantity of experimentation needed:
Due to the large quantity of experimentation necessary to determine if all plasma
cell ablating agents (in combination with an IL-4/IL-13 pathway inhibitor) reduce/eliminate allergen-specific serum IgE; treat allergy; prevent/reduce severity of an
allergic reaction to an allergen; and prevent generation of new IgE+ plasma cells; the
lack of direction/guidance presented in the specification regarding the same; the
complex nature of the invention; the unpredictability of the effects of all plasma cell
ablating agents and an IL-4/IL-13 pathway inhibitor on allergies and allergic reactions;
and the breadth of the claims, the skilled artisan would not know how to make and use
the invention recited in claims in its full scope.
Conclusion
Claims 1-3, 5, 12-25 and 43-45 are rejected.
Claims 36-42 are 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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to GYAN CHANDRA whose telephone number is (571)272-2922. The examiner can normally be reached Mon-Friday 8:30AM-5:00P.
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/GYAN CHANDRA/Primary Examiner, Art Unit 1674
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