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 Application/Amendments/Claims
Applicant’s response filed on 7/1/2026 has been considered. Claims 29-32 have been canceled. Claims 42-46 are currently withdrawn with traverse from further consideration pursuant to 37 CFR 1.142 (b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Claims 28 and 33-46 are pending. Claims 28 and 41 have been amended. Claims 28 and 33-41 are the subject of the present Official action. The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Priority
Applicant’s claim for the benefit of a prior-filed application CON of 16/336,635, PRO 62/399,775 and 371 of PCT/US2017/053453 filed on 3/26/2019, 9/26/2016 and 9/26/2017, respectively, under 35 U.S.C 119(e) or under 35 U.S.C 120, 121 or 365(c) is acknowledged.
Accordingly, the effective priority date of the instant application is granted as 9/26/2016.
Withdrawn Claim Rejections
The 35 U.S.C. 112(b) rejection of claim 41 is withdrawn in light of applicants claim amendments which provide proper antecedent basis for the recited diseases.
The 35 U.S.C. 112(a) written description rejection of claims 28 and 33 is reapplied in modified form and maintained with respect to claims 34-41 to address applicants claim amendments.
New Claim Rejections - 35 USC§ 112(a), Written Description
The following is a quotation of the first paragraph of 35 U.S.C. 112(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 28 and 33-41 are rejected in modified form 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, for pre-AIA the inventor(s), at the time the applicant was filed, had possession of the claimed invention. This claim rejection is supported by Freeman et al. US 2015/0210769, published 7/30/2015 (hereinafter Freeman, reference of record). This rejection is applied in modified form for claims 28 and 33 and maintained with respect to claims 34-41 to address applicants claim amendments. A response to applicant’s traversal is found below.
The claimed invention embraces the use of an inhibitor of TIGIT, PD-1, TIM-1, TIM-3, LAG-3, or CTLA-4 activity or expression in B cells. Dependent claims define either the moiety that binds the surface receptor as an antigen binding domain of an antibody specific for the B cell surface receptor/polypeptide marker OR the moiety that binds and inhibits TIGIT, PD-1, TIM-1, TIM-3, LAG-3, or CTLA-4 as an antigen binding domain of an antibody. Although applicant has amended the inhibitor to comprise an antibody or antigen-binding fragment that specifically binds to TIGIT, PD-1, TIM-1, TIM-3, LAG-3, or CTLA-4, the claims still generically recite a B cell targeting moiety. Importantly, no claim defines BOTH moieties as antigen binding domains beyond merely reciting a genetic moiety as part of the inhibitor. Thus, all claims rejected herein recite at least one generic moiety as part of the inhibitor as the active ingredient.
For each claim drawn to a genus, the written description requirement may be satisfied through sufficient description of a representative number of species by actual reduction to practice, reduction to drawings, or by disclosure of relevant identifying characteristics, i.e. structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in procession of the claimed genius. See Eli Lilly, 119F.3d at 1568, 43 USPQ2d at 1406. If a representative number of adequately descried species are not disclosed for a genus, the claim to that genus must be rejected as lacking adequate written description under 35 U.S.C. 112, para. 1.
The claims are considered to embrace the use of an extraordinary broad variety of moieties belonging to different and in some cases unrelated classes of molecular moieties that could putatively comprise the inhibitor which comprises a multispecific binding agent. Such classes embrace by this language include the recited antigen-binding domain of an antibody that specifically recognizes any of TIGIT, PD-1, TIM-1, TIM-3, LAG-3, or CTLA-4 OR CD19, CD20 or CD22, but also includes antisense RNA, siRNA, shRNA or any aptamer recognizing the same, any small organic molecule, dominant negative mutant, peptide/fragment inhibitor, ect. The breath of inhibitors encompassed by the instant claims is thus extraordinarily broad.
The instant specification broadly and prophetically contemplates TIGIT, PD-1, TIM-1, TIM-3, LAG-3, or CTLA-4 inhibitors such as antibodies including antigen-binding portions of antibodies such as epitope or antigen binding peptides, paratopes, functional CDRs, recombinant antibodies, chimeric antibodies, tribodies, small molecules, recombinant proteins, peptides, among others. However, outside of antigen-binding domains of antibodies that specifically recognize TIGIT, PD-1, TIM-1, TIM-3, LAG-3, or CTLA-4 inhibitor CD19, CD20 or CD22 surface markers, the specification does not exemplify any or in any other manner provide a disclosure of any other such structures of binders/inhibitors. Such inhibitors are only recited generically and at a high level. It is well known by those of ordinary skill in the art that development of small molecule inhibitors, aptamers, protein fragments rely on unpredictable trial and error experimentation. Thus, the instant specification’s recitation at a high level of generic binding agents and/or inhibitors is not considered to comprise a sufficient disclosure by way of precise definition of structure, formula, chemical name or physical properties of any molecule outside of antigen-binding domains of antibodies that specifically recognize TIGIT, PD-1, TIM-1, TIM-3, LAG-3, CTLA-4, CD19, CD20 or CD22 that are capable of comprising a moiety that is part of a multispecific agent that binds and/or inhibits these targets.
For example, the prior art shows that there are numerous antibodies or portions thereof capable of binding as inhibitors to PD-1, TIM-1, TIM-3, LAG-3 as shown by Freeman et al. US 2015/0210769, published 7/30/2015 (Freeman, para 62). However, none of the disclosed embodiments support the full breath of claims that encompass molecules as diverse as small molecule inhibitors and/or aptamers among many others. The examiner thus considers the combination of the instant specification and the prior art to be silent with regard to sufficient disclosure by way of structure, formula, chemical name or physical properties of any other molecule outside of antigen-binding domains of antibodies disclosed presently that might have been available at the time of applicant’s filing. Should applicant disagree, applicant is invited to point out with particularity where such examples might exist. In lack of such indication, these examples of the instant specification and prior art cannot be considered to support a finding of sufficient disclosure by way of precise definition of structure, formula, chemical name or physical properties of any molecule outside of antigen-binding domains of antibodies that specifically recognize TIGIT, PD-1, TIM-1, TIM-3, LAG-3, CTLA-4, CD19, CD20 or CD22 for inclusion in the inhibitor as required to practice the invention.
It is a fundamental tenet of the written description requirement that applicants may not preempt future discoveries by claiming an invention that is not considered to be in their possession at the time of filing. Given the breadth of the genus in contrast to the largely prophetic portions of the specification, the instant specification does not adequately disclose a sufficient number of described species of the genus to support the claim to all inhibitors which bind to TIGIT, PD-1, TIM-1, TIM-3, LAG-3 or CTLA-4 in B cells, and the specification lacks adequate written description for this genus therefore.
Response to Traversal
Although the rejection is newly applied in modified form, some of applicant’s arguments are still relevant and are addressed below.
Applicant traverses the instant rejection by arguing that the specification describes the characteristics and structures of antibody reagents and how to make them. Thus, the art was in possession of the genus recited and thus fulfills the requirements of the written description requirements. Applicant further points to the prior art and a PTAB decision which are argued to support that the claims herein are directed to a new use of existing inhibitors (antibodies).
These arguments have been fully considered, but are not found persuasive since all claims define either the moiety that binds the surface receptor as an antigen binding domain of an antibody specific for the B cell surface receptor/polypeptide marker OR the moiety that binds and inhibits TIGIT, PD-1, TIM-1, TIM-3, LAG-3, or CTLA-4 as an antigen binding domain of an antibody. Although applicant has amended the inhibitor to comprise an antibody or antigen-binding fragment that specifically binds to TIGIT, PD-1, TIM-1, TIM-3, LAG-3, or CTLA-4, the claims still generically recite a B cell targeting moiety. Importantly, no claim defines BOTH moieties as antigen binding domains beyond merely reciting a genetic moiety as part of the inhibitor. Thus, all claims rejected herein recite at least one generic moiety as part of the inhibitor as the active ingredient. It is a fundamental tenet of the written description requirement that applicants may not preempt future discoveries by claiming an invention that is not considered to be in their possession at the time of filing. Given the breadth of the genus in contrast to the largely prophetic portions of the specification, the instant specification does not adequately disclose a sufficient number of described species of the genus to support the claim to all inhibitors which bind to TIGIT, PD-1, TIM-1, TIM-3, LAG-3 or CTLA-4 in B cells, and the specification lacks adequate written description for this genus.
New Claim Rejections - 35 USC § 112b
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 28 and 33-41 are newly 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 pre-AIA the applicant regards as the invention. This rejection is newly applied to address applicants claim amendments filed on 7/1/2026.
The claimed invention embraces the use of an inhibitor of TIGIT, PD-1, TIM-1, TIM-3, LAG-3, or CTLA-4 activity or expression in B cells. It is unclear if “activity” and “expression” applies to each of the listed genes or just CTLA-4. Furthermore, it is unclear if the term “expression” applies to the inhibitor, the cell-surface receptor (TIGIT, PD-1, TIM-1, TIM-3, LAG-3, or CTLA-4) or the B cells themselves. As a result, one of ordinary skill in the art would not understand what the inhibitor is acting on. Please note that the language of a claim must make it clear what subject matter the claim encompasses to adequately delineate its "metes and bounds", see MPEP 2173.
Claim 33 is newly 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 pre-AIA the applicant regards as the invention. This rejection is newly applied to address applicants claim amendments filed on 7/1/2026.
Claim 33 depends on the canceled method of claim 32, wherein the B-cell specific cell surface markers are selected from CD19, CD20 and CD22. Claim 33 is indefinite for depending on canceled claim 32. As a result, one of ordinary skill in the art would not understand how the B-cell specific cell surface markers relate to the claimed method. Please note that the language of a claim must make it clear what subject matter the claim encompasses to adequately delineate its "metes and bounds", see MPEP 2173.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any extension fee pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ALEXANDER NICOL whose telephone number is (571)272-6383. The examiner can normally be reached on M-F 8-5 EST.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Maria Leavitt can be reached on (571)272-1085. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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Alexander Nicol
Patent Examiner
Art Unit 1634
/ALEXANDER W NICOL/Examiner, Art Unit 1634
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