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 .
Applicant’s election without traverse of group I, claims 52-54, in the reply filed on 10/21/25, is acknowledged. Applicant has elected embodiment CX., directed to a fusion protein comprising SEQ ID NO: 10, anti-CD19, and IL-2, as the species of fusion protein. Claim 55 is withdrawn as being directed to a non-elected invention.
Claims 52-54 are being acted upon.
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 52-54 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 claim 52 is improper because the 1620 alternatives defined in embodiments I. through MDCXX. do not share both a single structural similarity and a common use for the following reasons:
Each of the embodiments have either a distinct IL-10 amino acid sequence, a distinct VH/VL specificity, or a distinct Z cytokine moiety. For example, embodiment I.) has Z as IL-1, whereas embodiment IV.) is directed to Z as IL-4, and these cytokines are structurally and functionally distinct. Likewise, embodiment I). has CDRs from a CD19 as the monoclonal antibody, whereas embodiment DCCXLI.), for example, has CDRs from a CXCR4 antibody. These antibodies are structurally distinct and bind to functional and structurally distinct targets. Likewise, the embodiments differ in IL-10 sequence, and the claims encompass structurally distinct IL-10 sequences (for example, SEQ ID NO: 10 is less than 50% homologous to SEQ ID NO: 5). Therefore, each of the claimed embodiments are structurally and functionally distinct and do not share a substantial structural feature and a common use that flows from said structural feature. Furthermore, the fusion proteins are not discloses as known in the art to be functionally equivalent or as belonging to the same art recognized class .
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.
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 52-54 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.
Claim 52 is indefinite in the recitation that the anti-Ebola antibody “includes 3 light chain CDRs and 3 heavy chain CDRs that are engrafted with 3 light chain CDRs and 3 heavy chain CDRs from a second monoclonal antibody”. The scope of the claims is unclear and indefinite, because it is not clear if the claim intends to require a VH and VL domain with two sets of CDRs, with CDRs from both the first and second antibody, or whether the claim intends that the CDRs of the anti-Ebola first antibody are replaced with the CDRs of the second antibody. The specification on page 3 teaches an embodiment wherein human anti-Ebola antibodies were engrafted (i.e. replacing the 6 CDRs from one antibody with 6 CDRs from a second antibody). However, this does not appear to be a limiting definition and the ordinary meaning of the term “engrafted” would encompass joining or incorporating two things. Furthermore, in the instant case, the claims explicitly state that the proteins comprise a VH and VL region from an anti-Ebola antibody, wherein the VL and VH “include 3 light chain CDRs and 3 heavy chain CDRs”. This appears to require the presence of the CDRs from the anti-Ebola antibody. Furthermore, the claim also recite that the X moiety in the fusion protein is a VH and VL “from a first monoclonal antibody wherein the first monoclonal antibody is an anti-Ebola antibody”. The CDRs of an antibody VH and VL are responsible for binding specificity, and replacing the CDRs from an anti-Ebola antibody with CDRs from a different antibody would result in a VH and VL that no longer binds Ebola. Therefore it is unclear how the claim can require, for example, a VH region from a first anti-Ebola antibody, as recited in lines 5-6, and also require that the CDRs have been replaced with CDRs from an antibody of a different specificity, such as CD19. In other words, the claim language appears to require both sets of CDRs from each of the first and second antibody, but given the specifications exemplification of engrafting by replacing CDRs, the scope of the claims cannot be established.
Claim 53 recites the limitation "the framework region" in line 2. There is insufficient antecedent basis for this limitation in the claim.
The following is a quotation 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 35 U.S.C. 112 (pre-AIA ), first paragraph:
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 52-54 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 pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention. This is a new matter rejection.
The specification and the claims as originally filed do not provide support for the invention as now claimed, specifically:
A dual cytokine fusion protein wherein the second antibody is an “anti-B7H4 monoclonal antibody”
A review of the specification fails to reveal support for the new limitations.
The specification discloses a second antibody that is anti-B7-H3, but does not disclose anti-B7H4.
The following commonly assigned U.S. Patents by the same inventor of the instant application claim dual cytokine fusion proteins comprising IL-10:
US 11292822, US 11572397, US 11608368, US 11613563 B2, 11618775, US 11629178, US 12006346, US 12110317, US 1211639, US 12116392, US 12116391, US 12116390, US 12116389, US 12122814, US 12121755, US 12145007, US 12263358, and US 12268903 B2.
However, the fusion proteins claimed in the patents listed above all differ with respect the specificity of the second antibody (with some also differing with respect to the Z moiety and the IL-10 sequence). None of the issued patents claim a second antibody that is a CD19 antibody, which is the elected species under examination in the present application. The claims issued in the patents do not anticipate or render obvious the claims of the instant application.
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure. US 2020/0283488.
The ‘488 publication teaches IL-10 cytokine fusion proteins comprising an IL-10 identical to SEQ ID NO: 10 of the instant specification, wherein the fusion proteins have a formula of IL-10-X1-X2-IL-10, wherein X1 and X2 are antibody VH and VL. However, the ‘488 publication does not teach or suggest a fusion protein wherein Z, which is a cytokine other than IL-10, is between said VH(X1) and VL(X2).
The prior art does not teach or suggest the elected species of dual cytokine fusion protein of formula NH2-(IL-10)-(X')-(Zn)-(X2)- (IL-10)-COOH; wherein "IL-10" is a monomer; "X1 is a VL or VH region from a first monoclonal antibody; "X2" is a VH or VL region from the first monoclonal antibody; wherein when X1 is a VL, X2 is a VH or when X1 is a VH, X2 is a VL; wherein the first monoclonal antibody is an anti-Ebola antibody; wherein the VL and VH from the anti-Ebola antibody include 3 light chain CDRs and 3 heavy chain CDRs that are engrafted with 3 light chain CDRs and 3 heavy chain CDRs from a second monoclonal antibody;
wherein the IL-10 is SEQ ID NO: 10, the second antibody is an anti-CD19 monoclonal antibody, and Z is IL-2.
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to AMY E JUEDES whose telephone number is (571)272-4471. The examiner can normally be reached on M-F from 7am to 3pm.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Dan Kolker, can be reached at telephone number 571-272-3181. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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Amy E. Juedes
Patent Examiner
Technology Center 1600
/AMY E JUEDES/Primary Examiner, Art Unit 1644