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 .
Claim Status
Applicant’s claims received 11AUG2023 are acknowledged.
Claims 1-10 are pending in the instant application (i.e., Claim 1 is independent).
Priority
The present application is a 371 National Stage of PCT International Application No. PCT/US2022/016603, filed 16FEB2022, which claims the benefit of US Provisional Patent Application No. 63/150403, filed 17FEB2021. Applicant’s claim for the benefit of prior-filed application is acknowledged.
Information Disclosure Statement
The information disclosure statement(s) (IDS) submitted on 28MAR2024 (3x) is/are acknowledged and the references cited therein have been considered.
Drawings
The drawings filed 11AUG2023 are objected to because it is difficult to differentiate the variables in the drawings as related to the legend due to similarities of line size, line boldness, and symbols in Fig 1A, 3A-3B, 4B-4C, and 4E. Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Specification
The disclosure is objected to because of the following informalities:
In the Working Examples section, there are two sets of Example 4 at ¶0085 and ¶0089.
Appropriate correction is required.
Claim Objections
Claims 1-10 are objected to because of the following informalities:
Claim 1 contains the acronym LAIR1. While acronyms are permissible as shorthand in the claims, the first recitation of the term should include the full recitation followed by the acronym in parentheses Claims 2-10 are also objected to since they depend from claim 1, but do not remedy this deficiency.
Claims 5-10 are objected to under 37 CFR 1.75(c) as being in improper form because a multiple dependent claim cannot depend from any other multiple dependent claim. See MPEP § 608.01(n).
Claims 8-9, should be updated to “…wherein the antibody comprises HCDRs 1-3 consisting of SEQ ID NOs: xx-xx and LCDRs 1-3 consisting of SEQ ID NOs: yy-yy.” or of similar nature for the purpose of clarity.
Claim 9 contains a typographical error, “…of any one or claims…” should be updated to “…of any one of claims…” in line 1.
Appropriate correction 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.
Claims 4-10 are 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. In this instance, claim 4 recites, the method of any one of claims 1-4 (i.e., the claim is inclusive of itself) and therefore fails to further limit the subject matter. Claim 5 has the same issue. Claims 6-10 are also rejected since they depend from claims 4 or 5, but do not remedy this deficiency. Furthermore, claim 10, is broader than claim 6 upon which it depends (i.e., claim 10 fails to limit the subject matter of the claim upon which it depends). 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. In the interest of compact prosecution, claims 5-10 are being examined as if they depend directly from independent claim 1 for the remainer of this office action.
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.
Scope of Enablement
Claims 1-10 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 anti-PD1 resistant glioblastoma, comprising administering a therapeutically effective amount of total body irradiation prior to administering a therapeutically effective amount of an anti-LAIR1 antibody comprising HCDRs1-3 set forth in SEQ ID NOs: 10-12, respectively and LCDRs1-3 set forth in SEQ ID NOs: 13-15, respectively to a subject suffering from anti-PD1 resistant glioblastoma; or
A method of treating anti-PD1 resistant glioblastoma, comprising administering a therapeutically effective amount of total body irradiation prior to administering a therapeutically effective amount of an anti-LAIR1 antibody comprising HCDRs1-3 set forth in SEQ ID NOs: 10-12, respectively and LCDRs1-3 set forth in SEQ ID NOs: 13-15, respectively to a subject suffering from anti-PD1 resistant glioblastoma, wherein the method further comprises administering a therapeutically effective amount of CD70 CART cell therapy to the subject prior to administration of TBI;” does not reasonably provide enablement for more. 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.
In the instance of claim 1 drawn to a method of treating any checkpoint inhibitor resistant cancer by administering any anti-LAIR1 antibody to a subject suffering from any CPI resistant cancer is not fully enabled. The broadest claim is not fully enabled because:
The use of an anti-LAIR1 antibody to treat a subject resistant to any CPI therapy lacks support in the specification because LAIR1 is considered an immune checkpoint and an anti-LAIR1 antibody would therefore be considered a CPI therapy (Tao, et al., Neuro-oncology, 2023, 25, 228); however, Examiner notes that there is support in the specification for using an anti-LAIR antibody comprising HCDRs1-3 set forth in SEQ ID NOs: 10-12, respectively and LCDRs1-3 set forth in SEQ ID NOs: 13-15, respectively to treat an anti-PD1 resistant cancer (i.e., specific CPI therapy resistant cancer), specifically in glioblastoma;
The breadth of anti-LAIR1 antibodies;
The lack of support in the specification and working examples that the anti-LAIR1 antibody set forth in HCDR/LCDR 1-3 pairs set forth in SEQ ID NOs: 16-18 or 19-21 is equally effective in treating anti-PD1 resistant glioblastoma cancer as the antibody comprising HCDRs1-3 set forth in SEQ ID NOs: 10-12, respectively and LCDRs1-3 set forth in SEQ ID NOs: 13-15 used in the working examples;
In the broader method and the method further comprising, there is no support wherein TBI was not administered prior to anti-LAIR1 antibody treatment; and
The undue experimentation necessary to make the anti-LAIR1 antibody and use it in a method of treating any CPI resistant cancer. Claims 2-10 are rejected since they depend upon claim 1, but do not fully remedy this deficiency.
The specification discloses that three different antibodies may be used in the method of treating anti-PD1 CPI resistant cancer comprising HCDR/LCDR 1-3 pairs set forth in SEQ ID NOs: 10-12/13-15 or 16-18/19-21 or the antibody disclosed in WO 2018/126259 (The Board of Regents of the Univ of Texas System, et al., 05JUL2018, included in IDS) (¶0034-0036). Working example 3 of the specification discloses that administration of TBI and anti-LAIR1 antibody comprising HCDR/LCDR 1-3 pairs set forth in SEQ ID NOs: 10-12/13-15 resulted in inhibited tumor growth (Fig 3A) and 100% survival after more than 80 days (Fig 3B) in mice inoculated with anti-PD1 resistant glioblastoma (¶0082-0084). Furthermore, working example 5 teaches that there was a synergistic response when CD70 CART cell therapy was administered prior to the TBI and anti-LAIR1 antibody regimen as opposed to treating with CD70 CART cell therapy alone. Although these examples support that a method of treating a subject with anti-PD1 resistant glioblastoma comprising administering TBI prior to administering anti-LAIR1 antibody comprising HCDR/LCDR 1-3 pairs set forth in SEQ ID NOs: 10-12/13-15 or further comprising administering CD70 CART cell therapy prior to TBI and anti-LAIR1 antibody, it is unclear whether the same results could be observed without the TBI, using an alternative antibody, or for any CPI resistant cancer. Therefore, there is no disclosure or guidance provided regarding making the anti-LAIR1 antibody and using said antibody alone in the treatment of any CPI resistant cancer.
Furthermore, WO 2018/126259 (The Board of Regents of the Univ of Texas System, et al., 05JUL2018, included in IDS) teaches in working example 5 that of the 106 anti-LAIR1 antibodies tested, there were only four potential antagonistic antibodies which were able to block the LAIR1-collagen interaction (i.e., the proposed mechanism of action in the instant application) (p 99-100 and Fig 53D and 53E). Therefore the literature supports that there is a lack of predictability that all anti-LAIR1 antibodies will treat anti-PD1 resistant cancers.
Thus, one skilled in the art would be unable to make any anti-LAIR1 antibody and use said antibody alone or in addition to CD70 CART cell therapy in a method to treat any CPI resistant cancer without the addition of TBI. Therefore, the implementation of the invention in view of the unclear nature (i.e., efficacy of all anti-LAIR1 antibodies, efficacy of the specific anti-LAIR1 antibody used in essentially any CPI resistant cancer), breadth of variables (i.e., anti-LAIR1 antibody or CPI resistant cancer), lack of direction provided by the working examples, and lack of predictability in the art, would require undue experimentation for one of ordinary skill in the art to make and use the instantly claimed invention.
Written Description
Claims 1-7 and 10 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 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.
MPEP § 2163 states that the written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, 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 possession of the claimed genus. A “representative number of species” means that the species which are adequately described are representative of the entire genus. See, e.g., AbbVie Deutschland GMBH v. Janssen Biotech, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014). Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus to provide a "representative number” of species. 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.
In The Regents of the University of California v. Eli Lilly (43 USPQ2d 1398-1412) 19 F. 3d 1559, the court held that disclosure of a single member of a genus (rat insulin) did not provide adequate written support for the claimed genus (all mammalian insulins). In this same case, the court also noted: “A definition by function, as we have previously indicated, does not suffice to define the genus because it is only an indication of what the gene does, rather than what it is. See Fiers, 984 F.2d at 1169-71, 25 USPQ2d at 1605-06 (discussing Amgen). It is only a definition of a useful result rather than a definition of what achieves that result. Many such genes may achieve that result. The description requirement of the patent statute requires a description of an invention, not an indication of a result that one might achieve if one made that invention. See In re Wilder, 736 F.2d 1516, 1521, 222 USPQ 369, 372-73 (Fed. Cir. 1984) (affirming rejection because the specification does “little more than outlin [e] goals appellants hope the claimed invention achieves and the problems the invention will hopefully ameliorate."). Accordingly, naming a type of material generally known to exist, in the absence of knowledge as to what that material consists of, is not a description of that material.”
The court has further stated that “Adequate written description requires a precise definition, such as by structure, formula, chemical name or physical properties, not a mere wish or plan for obtaining the claimed chemical invention.” Id. at 1566, 43 USPQ2d at 1404 (quoting Fiers, 984 F.2d at 1171, 25 USPQ2d at 1606). Also see Enzo-Biochem v. Gen-Probe 01-1230 (CAFC 2002). Recent court cases have emphasized the need for correlation between a well-defined structure and recited functional limitations. For example, the courts have indicated that recitation of an antibody which has specific functional properties in the absence of knowledge of the antibody sequences that give rise to said functional properties do not satisfy the requirements for written description. See for example AbbVie Deutschland GmbH v. Janssen Biotech. Inc. 759 F.3d 1285 (Fed. Cir. 2014) as well as Amgen v. Sanofi, (Fed Cir, 2017-1480. 10/5/2017). Indeed, in Amgen the court indicates that that it is improper to allow patentees to claim antibodies by describing something that is not the invention, i.e., the antigen, as knowledge of the chemical structure of an antigen does not give the required kind of structure-identifying information about the corresponding antibodies, with the antibody-antigen relationship be analogized as a search for a key on a ring with a million keys on it. As such, knowledge of where an antibody binds provides no information as to what such an antibody necessarily looks like (i.e., its primary amino acid structure). Applicant is reminded that the courts have long ruled that “Possession may not be shown by merely describing how to obtain possession of members of the claimed genus or how to identify their common structural features.” See University of Rochester, 358 F.3d at 927, 69 USPQ2d at 1895. As such, disclosure of a screening assay to test for functional properties of a reagent (such as the epitope to which the reagent binds or the fact that it does or does not inhibit some process) does not provide evidence of possession of the reagent itself.
In Amgen Inc. v. Sanofi, 124 USPQ2d 1354 (Fed. Cir. 2017), relying upon Ariad Pharms., Inc. v. Eli Lily & Co., 94 USPQ2d 1161 (Fed Cir. 2010), the following is noted. To show invention, a patentee must convey in its disclosure that they “had possession of the claimed subject matter as of the filing date. Demonstrating possession “requires a precise definition” of the invention. To provide this precise definition” for a claim to a genus, a patentee must disclose “a representative number of species within the scope of the genus of structural features common to the members of the genus so that one of skill in the art can visualize or recognize the member of the genus” (see Amgen at page 1358). Further, an adequate written description must contain enough information about the actual makeup of the claimed products – “a precise definition, such as structure, formula, chemic name, physical properties of other properties, of species falling with the genus sufficient to distinguish the gene from other materials”, which may be present in “functional terminology when the art has established a correlation between structure and function” (Amgen page 1361). Indeed, the courts have long ruled that “When a patent claims a genus using functional language to define a desired result, the specification must demonstrate that the applicant has made a generic invention that achieves the claimed result and do so by showing that the applicant has invented species sufficient to support a claim to the functionally-defined genus.” See Capon v. Eshhar, 418 F.3d 1349 (Fed. Cir. 2005). Also, “A sufficient description of a genus . . . requires the disclosure of either a representative number of species falling within the scope of the genus or structural features common to the members of the genus so that one of skill in the art can "visualize or recognize" the members of the genus.” See AbbVie, 759 F.3d at 1297, reiterating Eli Lilly, 119 F.3d at 1568-69. It should also be noted that the USPTO has released a Memo on the Clarification of Written Description Guidance For Claims Drawn to Antibodies and Status of 2008 Training Materials, 02/22/2018. See https://www.uspto.gov/sites/default/files/documents/amgen_22feb2018.pdf. This Memo clarifies the applicability of USPTO guidance regarding the written description requirement of 35 U.S.C. § 112(a) concerning the written description requirement for claims drawn to antibodies and states: “In view of the Amgen decision, adequate written description of a newly characterized antigen alone should not be considered adequate written description of a claimed antibody to that newly characterized antigen, even when preparation of such an antibody is routine and conventional”. Further, the courts have indicated that the enablement and written description requirements of 35 USC 112 are separable as can be seen in for example Vas-Cath Inc. v. Mahurkar, 19 USPQ2d 1111.
Applicant has broadly claimed a method of treating any checkpoint inhibitor resistant cancer by administering any anti-LAIR1 antibody to a subject suffering from any CPI resistant cancer. The broadest claims do not require the anti-LAIR1 antibody to have any function apart from binding LAIR1 in a CPI resistant cancer, with dependent limitations adding additional functional limitations, such as, the epitope which the antibody binds. No claims recite any specific or particular structure of the anti-LAIR1 antibody that gives rise to the specific treatment functions upon administration to a subject, apart from claims 8 and 9, which are limited to six nondegenerate CDRs for each anti-LAIR1 antibody claimed.
To support such broad claims, the specification teaches three different antibodies may be used in the method of treating anti-PD1 CPI resistant cancer comprising HCDR/LCDR 1-3 pairs set forth in SEQ ID NOs: 10-12/13-15 or 16-18/19-21 or the antibody disclosed in WO 2018/126259 (The Board of Regents of the Univ of Texas System, et al., 05JUL2018, included in IDS) (¶0034-0036). Although the claims are drawn to any anti-LAIR1 antibody and any CPI resistant cancer, the experimental data teach administration of TBI and anti-LAIR1 antibody comprising HCDR/LCDR 1-3 pairs set forth in SEQ ID NOs: 10-12/13-15 resulted in inhibited tumor growth (Fig 3A) and 100% survival after more than 80 days (Fig 3B) in mice inoculated with anti-PD1 resistant glioblastoma (¶0082-0084) and that there was a synergistic response when CD70 CART cell therapy was administered prior to the TBI and anti-LAIR1 antibody regimen as opposed to treating with CD70 CART cell therapy alone.
With regard to antibodies, it should be pointed out that it is well established in the art that the formation of an intact antigen-binding site requires the association of the complete heavy and light chain variable regions of a given antibody, each of which consists of three different complementarity determining regions, CDR1, 2 and 3, which provide the majority of the contact residues for the binding of the antibody to its target epitope. The amino acid sequences and conformations of each of the heavy and light chain CDRs are critical in maintaining the antigen binding specificity and affinity which is characteristic of the parent immunoglobulin (Janeway, et al., Immunobiology: The Immune System in Health and Disease, 5th edition, 2001). It is also known that single amino acid changes in a CDR can abrogate the antigen binding function of an antibody (Rudikoff, et al., PNAS, 1982, 79, 1979-1983 see entire document, particularly the abstract and the middle of the left column of p 1982). Thus, based upon the prior art, skilled artisans would reasonably understand that it is the structure of the CDRs within an antibody which gives rise to the functional property of antigen binding, the epitope to which said CDRs bind is an inherent property which appears to necessarily be present due to conservation of critical structural elements, namely the CDR sequences themselves.
Artisans are well aware that knowledge of a given antigen (for instance a specific epitope of the ECD of LAIR1) provides no information concerning the sequence/structure of antibodies that bind the given antigen. For example, Edwards et al. teach that over 1,000 different antibodies to a single protein can be generated, all with different sequences spanning almost the entire heavy and light chain germline repertoire (42/49 functional heavy chain germlines and 33 of 70 V-lambda and V-kappa light chain germlines, and with extensive diversity in the HCDR3 region sequences (that are generated by VDJ germline segment recombination) as well (Edwards, et al., J Mol Biol, 2003, 334, 103-118, see entire document). Goel et al. disclose the synthesis of three monoclonal antibodies that bind to the same short (12-mer) peptide and found that the sequences of these antibodies which bound the same epitope exhibited diverse V gene usage indicating their independent germline origin (Goel, et al., J Immunol, 2004, 173, 7358-7367, see entire document). Further, it should be noted that degenerate binding of the same structural motif by antibodies does not require the existence of sequence homology or identity at any of their CDRs or other chemical similarities at the antigen-binding sites; side chain mobility of epitope residues can confer steric and electrostatic complementarity to differently shaped combining sites, allowing functional mimicry to occur (Lescar et al., J Biol Chem, 1995, 270, 18067-18076, see entire document, in particular Abstract and Discussion). As such, it does not seem possible to predict the sequence/structure of an antibody that binds a given antigen as there does not appear to be any common or core structure present within all antibodies that gives rise to the function of antigen binding. Further, given data such as that of Edwards et al. indicating the diversity of sequence bound in a population of antibodies that bind to a given antigen no number of species appears to reasonably representative of the breadth of the genus of antibodies that bind the given antigen.
It is noted that applicant has not claimed a product, but rather a method of administering a product. However, artisans must reasonably be in possession of a product in order to be in possession of methods of administering said product. As has been discussed above, the broadest claims describe the administered product based upon what it does, such as binding LAIR1 protein to treat CPI resistant cancer including at a particular epitope (i.e., see claim 7). However, as has been made clear by recent court cases as well as USPTO guidance, describing an antibody simply by what it binds is not sufficient to provide adequate written description for the recited genus. Indeed, as taught by Edwards et al., Lescar et al., and Goel et al., the number of potential antibody structures (i.e., sequences) which can bind to the same antigen is literally astronomical. As such describing the administered reagent based upon what it binds, where it binds, or its function as an inhibitor fails to necessarily provide a structure that gives rise to the aforementioned properties.
In this instance, the prior art supports six nondegenerate CDRs are necessary to define an antibody (i.e., anti-LAIR1 antibody). As presently written, the claims recite that any anti-LAIR1 antibody functions to bind LAIR1 and treat CPI resistant cancers upon administration. However, the specification and working examples fail to disclose any data indicating that the breadth of structures (i.e., any anti-LAIR1 antibody) encompassed by the language of the instant claims will have the same function (i.e., bind LAIR1 protein and can be used to treat any CPI resistant cancer upon administration to a subject suffering from any CPI resistant cancer). Therefore, one of ordinary skill in the art would reasonably conclude that the applicant was not in possession of the full breadth of the claimed genus of anti-LAIR1 antibodies that bind LAIR1 and can be used in a method to treat a subject having any CPI resistant cancer, including binding a specific epitope of LAIR1 (i.e., ECD of LAIR1), at the time the instant application was filed. Logically, if applicant was not in possession of the agent which is being administered, applicant also was not in possession of methods of administering such reagents at the time the instant application was filed.
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 1-2, 4-5, 7, and 10 rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-10 of U.S. Patent No. 11,377,491, herein referred to as “’491” in view of WO 2018/126259 (The Board of Regents of the Univ of Texas System, et al., 05JUL2018, included in IDS and the WIPO of the ‘491 patent), herein referred to as “’259” and Peng, et al., (Nature Commun, 2020, 11, 1-18, included in IDS), herein referred to as “Peng.”
The issued claims of the ‘491 patent recite: An isolated monoclonal antibody or an antigen-binding fragment thereof comprising (a) a heavy chain variable region comprising the following complementary determining regions (CDRs): a heavy chain CDR1 that is a CDR1 in SEQ ID NO: 1, 15, 29, 43, 57, 71, 85, 99, 113, 127, 141, 155, 169, 183, 197, 211, 225, 239, 253, 267, 281, 295, 309, 323, 337, 351, 365, 379, 393, 407, 421, 435, 449, 463, 477, 491, 505 or 519, a heavy chain CDR2 that is a CDR2 in SEQ ID NO: 1, 15, 29, 43, 57, 71, 85, 99, 113, 127, 141, 155, 169, 183, 197, 211, 225, 239, 253, 267, 281, 295, 309, 323, 337, 351, 365, 379, 393, 407, 421, 435, 449, 463, 477, 491, 505 or 519, and a heavy chain CDR3 that is a CDR3 in SEQ ID NO: 1, 15, 29, 43, 57, 71, 85, 99, 113, 127, 141, 155, 169, 183, 197, 211, 225, 239, 253, 267, 281, 295, 309, 323, 337, 351, 365, 379, 393, 407, 421, 435, 449, 463, 477, 491, 505 or 519; and (b) a light chain variable region comprising the following CDRs: a light chain CDR1 that is a CDR1 in SEQ ID NO: 2, 16, 30, 44, 58, 72, 86, 100, 114, 128, 142, 156, 170, 184, 198, 212, 226, 240, 254, 268, 282, 296, 310, 324, 338, 352, 366, 380, 394, 408, 422, 436, 450, 464, 478, 492, 506 or 520, a light chain CDR2 that is a CDR2 in SEQ ID NO: 2, 16, 30, 44, 58, 72, 86, 100, 114, 128, 142, 156, 170, 184, 198, 212, 226, 240, 254, 268, 282, 296, 310, 324, 338, 352, 366, 380, 394, 408, 422, 436, 450, 464, 478, 492, 506 or 520, and a light chain CDR3 that is a CDR3 in SEQ ID NO: 2, 16, 30, 44, 58, 72, 86, 100, 114, 128, 142, 156, 170, 184, 198, 212, 226, 240, 254, 268, 282, 296, 310, 324, 338, 352, 366, 380, 394, 408, 422, 436, 450, 464, 478, 492, 506 or 520 (i.e., claim 1), which references the CDRs of an anti-LAIR1 antibody (see Table 6 for SEQ ID number correlation).
However, they do not claim: a method of treatment comprising administering an anti-LAIR1 antibody to a subject suffering from a cancer that is resistant to CPI therapy or further comprising administering CART cell therapy.
Nevertheless, ‘259 teaches a method of treating a multiply drug resistant cancer inclusive of brain cancer (i.e., glioblastoma), comprising administering an anti-LAIR1 antibody that binds to amino acid residues 25-121 of LAIR1 (i.e., within amino acids 22-165 of LAIR1), wherein the antibody is humanized, and wherein the method further comprises administering a therapeutically effective amount of a second anti-cancer agent or treatment (i.e., CART cell therapy) (see entire document, specifically see claims 1, 5, 35, 40-42, ¶0017, and ¶00230). Furthermore, ‘259 teaches in working example 5 that four potential antagonistic antibodies were able to block the LAIR1-collagen interaction (p 99-100 and Fig 53D and 53E).
Additionally, Peng teaches that collagen promotes anti-PD1/PDL1 resistance in cancer through LAIR1-dependent T cell exhaustion and by abrogating LAIR1 immunosuppression, anti-PD1/PDL1 resistant tumors are sensitized to anti-PD1 therapy providing opportunities for therapeutic combinations (see entire document).
It would have been obvious to artisans to modify the issued anti-LAIR antibody as claimed by the ‘491 patent to include a method of treatment of an anti-PD1/PDL1 resistant cancer inclusive of brain cancer (i.e., glioblastoma), comprising administering an anti-LAIR1 antibody that binds to amino acid residues 25-121 of LAIR1 as taught by ‘259 (i.e., the WIPO of the issued ‘491 patent) and Peng. This is because ‘259 teaches that anti-LAIR1 antibodies can be effective in treating multiply drug resistant cancers by administration of an anti-LAIR1 antibody and Peng teaches that the collagen-LAIR1 interaction promotes anti-PD1/PDL1 resistance in cancer and by inhibiting said interactions provides the opportunity for therapeutic combinations for treating anti-PD1/PDL1 resistant tumors. One would have been motivated to do so, given the direction by the ‘491 patent that the product (i.e., anti-LAIR1 antibody) binds LAIR1 proteins. There would have been a reasonable expectation of success, given the knowledge that the anti-LAIR1 antibody product taught by the ‘491 patent could be used to bind LAIR1 proteins and upon administration to a subject treat a multiply drug resistant cancer as taught by ‘259 and Peng.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claims 1-2, 4-5, 7, and 10 are rejected under 35 U.S.C. 103 as being unpatentable over WO 2018/126259 (The Board of Regents of the Univ of Texas System, et al., 05JUL2018, included in IDS), herein referred to as “’259” and in view of Peng, et al., (Nature Commun, 2020, 11, 1-18, included in IDS), herein referred to as “Peng.”
‘259 teaches a method of treating a multiply drug resistant cancer inclusive of brain cancer (i.e., glioblastoma), comprising administering an anti-LAIR1 antibody that binds to amino acid residues 25-121 of LAIR1 (i.e., within amino acids 22-165 of LAIR1), wherein the antibody is humanized, and wherein the method further comprises administering a therapeutically effective amount of a second anti-cancer agent or treatment (i.e., CAR T cell therapy) (see entire document, specifically see claims 1, 5, 35, 40-42, ¶0017, ¶00230, and ¶00277). Furthermore, ‘259 teaches in working example 5 that four potential antagonistic antibodies were able to block the LAIR1-collagen interaction (p 99-100 and Fig 53D and 53E).
However, they do not teach: that the patient population is specifically resistant to checkpoint inhibitor therapy such as anti-PD1 therapy.
Nevertheless, Peng teaches that collagen promotes anti-PD1/PDL1 resistance in cancer through LAIR1-dependent T cell exhaustion, increased LAIR1 expression in patients treated with PD1 therapy predicted poorer survival and response, and by abrogating LAIR1 immunosuppression, anti-PD1/PDL1 resistant tumors are sensitized to anti-PD1 therapy providing opportunities for therapeutic combinations (see entire document).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of treating a multiply drug resistant cancer inclusive of brain cancer (i.e., glioblastoma), comprising administering an anti-LAIR1 antibody that binds to amino acid residues 25-121 of LAIR1 (i.e., within amino acids 22-165 of LAIR1), disclosed by ‘259 by specifically treating anti-PD1 resistant cancers by inhibiting the LAIR1-collagen interaction disclosed by Peng. One would have been motivated to do so, given the teachings of ‘259 that anti-LAIR1 antibodies inhibit the LAIR1-collagen interaction. There would have been a reasonable expectation of success, given the knowledge that anti-LAIR1 antibodies can be used to treat multiply drug resistant cancers, and in the instance of anti-PD1/PDL1 resistant cancers, which are promoted by the LAIR1-collagen interaction as taught by Peng, anti-LAIR1 antibodies which inhibit the LAIR1-collagen interaction would lead to a method of treating anti-PD1/PDL1 resistant cancers.
Allowable Subject Matter
Examiner notes that the six nondegenerate CDRs as set forth in specific SEQ ID NOs of claims 8 and 9 are free of the prior art.
Conclusion
No claims are allowed.
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/SAMANTHA LAKE HOPKINS/Examiner, Art Unit 1641
/MICHAEL SZPERKA/Primary Examiner, Art Unit 1641