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 .
Response to Amendment
The rejection of claims 7, 10 and 12 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, are moot in view of the cancellation of claims 7 and 10 and withdrawn in view of the deletion in claim 12 of the reference to “bispecific”.
The rejection of claims 1, 2, 5, 7, 9-11, 13, 14 and 20 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, for lacking enablement, is withdrawn in view of the amendment to claim 1 limiting the antibody to comprising SEQ ID NO:17 and 18. Note claims 12 and 15 remain rejected.
The rejection of claims 1, 2, 5, 7, 9-11, 13, 14 and 20 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112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement is withdrawn in view of the amendment to claim 1 limiting the antibody to comprising SEQ ID NO:17 and 18. Note claims 12 and 15 remain rejected.
Claim(s) 7 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by WO02014115430 AI (cited in the IDS filed 5/8/2023) is withdrawn in view of the cancellation of the claim.
The rejection of claims 3 and 4 under 35 U.S.C. 101 as claiming the same invention as that of claims 2, 3 and 4, respectively, of prior U.S. Patent No. 11,673,963 B2 is withdrawn in view of the amendment to claim 1 limiting the antibody to comprising SEQ ID NO:17 and 18.
Claim Interpretation
In the interest of compact prosecution, it is being assumed that both the antibody and antigen-binding fragment thereof comprise SEQ ID NO:17 and 18 (see claim 1). If they do not, then previous rejection under nonstatutory double patenting would remain because an antigen-binding fragment of SEQ ID NO:17 and 18 includes the variable heavy and light chains as set forth in claim 5 of US 11,673,963 B2 (see end of double patenting rejection below).
Claim Rejections - 35 USC § 112(b)
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 1 and dependent claims 11-15, and 20 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 1 is indefinite because it recites, ”An antibody, or an antigen-binding fragment thereof,.. said antibody, or antigen-binding fragment thereof, comprising a heavy chain comprising SEQ ID NO:17 and a light chain comprising SEQ ID NO:18. It is unclear if both the antibody and antibody-binding fragment thereof comprising SEQ ID NO:17 and 18. If they do, then it does not reasonably appear an antibody “fragment” can comprise a full heavy and full light chain as represented by the sequences. That is, reference to an antigen-binding fragment should be removed from all claims. In the interest of compact prosecution, it is being assumed that both the antibody and antigen-binding fragment thereof are intended to comprise SEQ ID NO:17 and 18 (see Claim Interpretation above). Clarity is required.
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.
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.
Claim 15 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. Because it appears that claim 1 now requires the full heavy and light chain sequences, which include the constant domain(s) thereof, dependent claim 15 is no longer further limiting because the antibody or antigen-binding fragment thereof cannot be Fab, Fab’, F(ab)2, F(ab’)2, Fv or scFv, which have no constant region. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
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.
Claims 12 and 15 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 an antibody or antigen-binding fragment thereof that binds CRTAM and comprises a heavy chain variable region (VH) comprising SEQ ID NO:13 and a light chain variable region (VL) comprising SEQ ID NO: 14 or a heavy chain (HC) of SEQ ID NO:17 and light chain (LC) of SEQ ID NO:18, does not reasonably provide enablement wherein the antibody or antigen-binding fragment thereof for claim 12 is a human antibody or for claim 15 is a single-domain antibody. 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 for the reasons set forth in the previous Office action and for the following reason addressing the amendment to claim 1: Because it reasonably appears now that the both the antibody and antigen-binding fragment thereof must comprise SEQ ID NO:17 and 18, this excludes wherein the product is a Fab, F(ab)2, F(ab’)2, Fv, and scFv because these do not have constant domains, which SEQ ID NO:17 and 18 do.
The factors considered when determining if the disclosure satisfies the enablement requirement and whether any necessary experimentation is undue include, but are not limited to: 1) nature of the invention, 2) state of the prior art, 3) relative skill of those in the art, 4) level of predictability in the art, 5) existence of working examples, 6) breadth of claims, 7) amount of direction or guidance by the inventor, and 8) quantity of experimentation needed to make or use the invention. In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988).
For claim 12, which includes wherein the antibody or antigen-binding fragment thereof is a human antibody or antigen-binding fragment, there is a lack of enablement for such a human antibody. The disclosed antibody, 5A11, was produced from rat immunized with human CRTAM extracellular domain as a monoclonal antibody and then humanized (Examples 1 and 6). Because the CDRs of 5A11 are from a rat antibody, it cannot be a human antibody even though it may have some human sequence (framework regions) and bind a human antigen (see, for example, Mallbris et al., J. Clin. Aesthet. Dermatol. 9(7):13-15, 2016, p. 15, col. 1, first paragraph, cited in the IDS filed 5/8/23).
The specification does not disclose any single-domain CRTAM antibodies. However, for claim 15 the antigen-binding fragment may be a single-domain antibody. The specification provides guidance or direction only for antibodies comprising both a heavy and light chain variable region, e.g., Fab, Fv, etc., antibody fragment. However, single-domain antibodies rely for binding on a single variable set of CDRs, usually derived by immunization of camels (Yan et al., J. Transl. Med. 12:343, 2014, cited in the IDS filed 5/8/23). Making a single-domain antibody that comprised the CDR-H1-3 of claim 1 based on the teaching of the instant specification would require undue experimentation. Additionally, assuming the antibody and antigen-binding fragment thereof of claim 1 both comprise full heavy and light chain sequences of SEQ ID NO:17 and 18, respectively, this excludes antibody fragments, including Fab, F(ab)2, F(ab’)2, Fv, and scFv, none of which comprise constant regions.
Therefore, for the reasons discussed above, including the lack of disclosure of a human antibody or any single-domain antibody meeting the claim limitations, it would require undue experimentation to make and use the invention commensurate in scope with the claims.
Claims 12 and 15 remain 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 for the reasons set forth in the previous Office action and as recast here to address the amendment to independent claim 1 and removal of all but claims 12 and 15 from the rejection.
The specification discloses rat antibody 5A11, which binds the extracellular domain of human CRTAM (p. 45, lines 27-29), and a humanized version thereof (Examples 1 and 6). The HC and LC of the humanized antibody have the sequences of SEQ ID NO:17 and 18, respectively. An antibody comprising these HC and LC meets the written description provision of 35 USC 112(a). However, the claims are directed to or encompass human and single-domain antibodies (claims 12 and 15), none of which are disclosed. These do not meet the written description provision of 35 USC 112(a). There are no prior art antibodies disclosed that meet the claim limitations. The skilled artisan could not readily envision or recognize these other encompassed antibodies or antigen-binding fragments thereof.
In reference to claim 15, the specification does not disclose any particular single-domain antibodies which bind CRTAM. One skilled in the art could envision a Fab, Fab’, F(ab)2, F(ab’)2, Fv or scFv given the knowledge of the full VH and VL of an antibody that bound CRTAM; although, these appear to be excluded from the claim (see Claim Interpretation above). However, single-domain antibody structures are distinct, with binding relying on a single variable set of CDRs, usually derived by immunization of camels (Yan et al., J. Transl. Med. 12:343, 2014, cited in the IDS filed 5/9/22). By definition there are no single domain antibodies comprising a HC and LC.
There is no description of a human antibody meeting the limitations of claim 12. The original antibody was isolated from an immunized rat (Example 1). The structural features common to the members of the genus needed for one of skill in the art to visualize or recognize the members of the genus takes into account the state of the art at the time of the invention. For antibodies, the Federal Circuit has found that possession of a mouse antibody heavy and light chain variable regions provides a structural "stepping stone" to the corresponding chimeric antibody, but not to human antibodies. Centocor Ortho Biotech, Inc. v. Abbott Laboratories, 636 F.3d 1341, 97 USPQ2d 1870 at 1875 (Fed. Cir. 2011) set forth that, “[T]he application only provides amino acid sequence information (a molecular description of the antibody) for a single mouse variable region, i.e., the variable region that the mouse A2 antibody and the chimeric antibody have in common. However, the mouse variable region sequence
does not serve as a stepping stone to identifying a human variable region within the
scope of the claims.”.
Vas-Cath Inc. v. Mahurkar, 19USPQ2d 1111 (Fed. Cir. 1991), clearly states that “applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the ‘written description’ inquiry, whatever is now claimed.” (See page 1117.) The specification does not “clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed.” (See Vas-Cath at page 1116).
Applicant is reminded that Vas-Cath makes clear that the written description provision of 35 U.S.C. § 112 is severable from its enablement provision (see page 1115).
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1, 11-15 and 20 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-10 and 15 of U.S. Patent No. 11,673,963 (‘963) as recast here to address the amendment to claim 1 reciting the full heavy and light chain sequences of respectively SEQ ID NO:17 and 18 and in view of US Patent No. 9,550,825 (Takada) and Mimoto et al. (Protein Eng. Design Select. 26(10):589-598, 2013).
Although the claims at issue are not identical, they are not patentably distinct from each other because they are all draw to an antibody or antigen-binding fragment thereof that binds CRTAM and comprises the heavy chain variable region (VH) of SEQ ID NO:13 and light chain variable region (VL) of SEQ ID NO:14 (claims 1-5 of ‘963). Instant claim 1 appears to require both the antibody and antigen-binding fragment thereof to comprise the heavy chain (HC) of SEQ ID NO:17 and light chain (LC) of SEQ ID NO:18, which is not claimed in ‘963. Claim 6 of ‘963 and instant claim 11 limit the antibody to a monoclonal. Instant claim 12 and ‘963 claim 7 include a chimeric or humanized antibody. Instant claim 14 and ‘963 claim 9 require the antibody be capable of inducing and/or enhancing T-cell cytotoxicity. Both instant claim 20 and ‘963 claim 15 are drawn to a pharmaceutical composition comprising the CRTAM-binding antibody. ‘963 differs because the encompassed full-length antibody of the claims therein does not have defined constant regions.
Takada teaches chimeric and humanized anti-HMGB1 antibody having HC of SEQ ID NO:13 and 39 and LC of SEQ ID NO:14 and 40, respectively. The constant regions of both the chimeric and humanized antibody are identical. The HC constant domain of Takada (amino acids 125-455 of SEQ ID NO:13 and 39) is identical to that of the instant HC (amino acids 119-449 of instant SEQ ID NO:17), with the exception of substitutions S267E and L328F by Kabat numbering found in the instant HC. The LC domain of Takada (amino acids 108-213 of SEQ ID NO:14 and 40) is identical to that of the instant LC (amino acids 109-214 of instant SEQ ID NO:18).
Mimoto et al. teaches (p. 589, col. 2, second and fourth paragraphs) engineered antibody Fc variants that selectively bind FcγRIIb, referred to as inhibitory, which have been reported to enhance the agonistic activity of anti-tumor necrosis factor receptor superfamily antibody and an anti-DR5 agonist antibody, theoretically by acting as a scaffold for efficient cross-linking of the antibodies to the target cells through FcγRIIb (see also p. 597, col. 1, start of third paragraph). Reference is made (sentence bridging pp. 589-599) to an earlier report showing, “Introducing S267E/L328F substitutions into the Fc region of human IgG1 increased the binding affinity to FcγRIIb 430-fold without increasing that to FcγRI, FcγRIIaH131 or FcγRIIIa (Chu et al., 2008).” Fig. 4 shows an antibody with S267E/L328Fdid not bind Fc receptor FcγRIIaH131 or F158 (Fig. 2).
It would have been obvious wherein the VH and VL of ‘963 had the corresponding HC and LC constant regions of Takada because substitution of one known element for another would have yielded predictable results to one of ordinary skill before the effective filing date of the invention. It further would have been obvious and desirable to include the S267E/L328F substitutions into the Fc region of the HC in order to increase binding affinity to FcγRIIb with the expectation of enhancing agonistic activity of the anti-CRTAM antibody. As a result, instant claim 13 and patent claim 8, both of which limit the antibody or antigen-binding fragment to a Fc silenced engineered IgG1, are not patentably distinct (see Mimoto Fig. 2).
In the event that Applicant intended for the claims not to be limited to an antibody or antigen-binding fragment thereof that both comprise SEQ ID NO:17 and 18, but instead encompass an antigen-binding fragment of instant SEQ ID NO:17 and 18, e.g., the VH and VL of the antibody, e.g., a Fab, Fab’, F(ab)2, F(ab’)2 or Fv antibody fragment, the claims are not patentably distinct between the instant application and ‘963.
Prior Art
The prior art made of record and not relied upon is considered pertinent to Applicant's disclosure.
US 2015/0361164 A1, cited in the IDS filed 10/16/2025, is the pregrant publication of US Patent 9,550,825 relied upon above.
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 nonprovisional extension fee (37 CFR 1.17(a)) 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.
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Claire Kaufman
/Claire Kaufman/
Primary Examiner, Art Unit 1674
January 22, 2026