DETAILED ACTION
Notice of Pre-AIA or AIA Status
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
2. Applicant’s election without traverse of Group I (claims 134-159 and 161-162) and species of (i) MHC I protein, (ii) melanoma and (iii) induction or enhancement of human CD137-mediated T cell activation and cytokine production, without inducing intrahepatic T cell activation or elevated ALT activity in the reply filed on 3/25/2026 is acknowledged.
3. Claims 134-162 are pending. Claims 160 and 148-154 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention/species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 3/25/2026.
4 Claims 134-147, 155-159 and 161-162 are under examination.
Information Disclosure Statement
5. The information disclosure statements (IDS) submitted on 10/31/2023, 2/14/2024, 3/21/2024, 5/9/2024, 7/22/2024, 12/3/2024 and 8/19/2025 have been considered.
Priority
6. Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. Applicant has not complied with one or more conditions for receiving the benefit of an earlier filing date under 35 U.S.C. 119(e), 120 and 121 as follows:
The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of 35 U.S.C. 112(a) or the first paragraph of pre-AIA 35 U.S.C. 112, except for the best mode requirement. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994).
The disclosure of the prior-filed applications, Application Nos. 16/895,239, 16/123,742, 16/032,639, 62/531,259, 62/531,190, 62/568,231, 62/577,257, and 62/577,259 fail to provide adequate support or enablement in the manner provided by 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph for one or more claims of this application.
Independent claims 134, 156, and 162 recite “wherein the subject has cancer cells that express MHC I”. Independent claim 157 recite “detecting MHC I in a subject having cancer”. Independent claims 158 and 159 recite “detecting the agent bound to MHC I, wherein the presence of MHC I indicates that the cancer is amenable to treatment with an agonist CD137 antibody, or antigen-binding fragment thereof”. All these limitations are not mentioned in the prior-filed applications. Therefore, the effective filing date of claims 134-147, 155-159 and 162 is the filing date of instant application, i.e. 8/4/2023.
New Matter
7. MPEP 201.06 states: the disclosure presented in a divisional application must not include any subject matter which would constitute new matter if submitted as an amendment to the parent application.
MPEP 201.07 states: The disclosure presented in the continuation must not include any subject matter which would constitute new matter if submitted as an amendment to the parent application
Instant application is a continuation of U.S. Patent Application Serial No. 16/895,239, which is a divisional of U.S. Patent Application Serial No. 16/123,742, which is a continuation of U.S. Patent Application Serial No. 16/032,639.
Independent claims 134, 156, and 162 recite “wherein the subject has cancer cells that express MHC I”. Independent claim 157 recite “detecting MHC I in a subject having cancer”. Independent claims 158 and 159 recite “detecting the agent bound to MHC I, wherein the presence of MHC I indicates that the cancer is amenable to treatment with an agonist CD137 antibody, or antigen-binding fragment thereof”. All these limitations are not mentioned in the prior-filed non-provisional applications and thus constitute new matter.
If applicant believes that support for the above-mentioned limitations is present in the prior filed applications, applicant must, in responding to this action, point out with particularity, where such support may be found.
Applicant is required to cancel the new matter, or change the application to continuation-in-part (CIP) of U.S. Patent Application Serial No. 16/895,239.
Specification
8. The specification is objected to as failing to provide proper antecedent basis for the claimed subject matter. See 37 CFR 1.75(d)(1) and MPEP § 608.01(o).
Specifically, the limitations “wherein the subject has cancer cells that express MHC I”. “detecting MHC 1 in a subject having cancer”. “detecting the agent bound to MHC1, wherein the presence of MHC I indicates that the cancer is amenable to treatment with an agonist CD137 antibody, or antigen-binding fragment thereof” are not mentioned in the specification.
Applicant is cautioned that such amendment is only permitted when the application is changed to CIP of US 16/895,239.
9. The specification is objected to because a sequence listing was filed on 3/15/2024, however the Incorporation by Reference paragraph required by 37 CFR 1.821(c)(1) has not been updated.
10. The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code, see page [0270] and [0271], for example. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code found throughout the specification. See MPEP § 608.01.
Drawings
11. The drawings filed on 8/4/2023 are objected to because Fig.3A comprises amino acid sequences that were not identified with corresponding sequence identifiers (SEQ ID NOs) within the figure or within the figure legend of the specification.
Claim Objections
12. Claims 161 and 162 are objected to as being dependent from a withdrawn claim.
Claim 142 is objected to because renal, colon, lung, prostate, breast, and hematological are not cancer. The word “cancer” should be added after each of these terms.
Claim Rejections - 35 USC § 101
13. 35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
14. Claim 158 is rejected under 35 U.S.C. 101 because the claimed invention is directed to a law of nature without significantly more.
According to the 2019 Revised Patent Subject Matter Eligibility Guidance published in the Federal Register (84 FR 50) on January 7, 2019, the claim meets step 1 as the instant claims are drawn to a process. The claim also meets prong one of step 2A because the claims recite the following law of nature or natural phenomenon: a correlation between the presence of MHC I and amenability of cancer to treatment with an agonist CD137antibody (see “wherein the presence of MHC I indicates that the cancer is amenable to treatment with an agonist CD137 antibody, or antigen-binding fragment thereof”). The claim does not meet prong two of step 2A because the combination of additional elements fails to integrate the judicial exception into practical application. The additional elements (beyond the judicial exceptions) are (i) contacting a biological sample comprising cancer cells from the subject with an agent directed to MHC I; and (ii) detecting the agent bound to MHC I. These elements do not apply, rely on or use the judicial exception in a manner that imposes a meaningful limit on the judicial exception.
According to 2019 PEG updates, limitations that are indicative of integration into a practical application when recited in a claim with a judicial exception include:
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Limitations that are not indicative of integration into a practical application when recited in a claim with a judicial exception include:
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In the instant case, steps (i) and (ii) are insignificant extra-solution activity. Data gathering steps required to use the correlation do not add a meaningful limitation to the method as they are insignificant extra-solution activity. The claim also fails to apply or use a judicial exception to effect a particular treatment or prophylaxis for disease or medical condition, or improve to the functioning of a compute or any other technology or technical field.
The claim also fails to meet step 2B because the additional elements were well known and conventional in the art as evidenced by Hanagiri et al. (J Surg Res. 2013, 181: e57-e63. Hanagiri et al. teaches detecting HLA class I (human MHC class I) protein expressed by lung cancer cells by immunohistochemistry using an antibody (page e58, column 2). Therefore, the additional steps/elements do not add significantly more to the judicial exception.
Since the claim as a whole does not include additional elements that are sufficient to amount to significantly more than the judicial exception, the claim is not directed to eligible subject matter under 35 U.S.C 101.
Claim Rejections - 35 USC § 112
15. 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.
16. Claims 138-140, 144-147, 155 and 157-159 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.
“[T]he purpose of the written description requirement is to ‘ensure that the scope of the right to exclude, as set forth in the claims, does not overreach the scope of the inventor’s contribution to the field of art as described in the patent specification.’” Ariad Pharm., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1353-54 (Fed. Cir. 2010) (en banc) (quoting Univ. of Rochester v. G.D. Searle & Co., 358 F.3d 916, 920 (Fed. Cir. 2004)). To satisfy the written description requirement, the specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention. Vas-Cath, Inc. v. Mahurkar, 935 F.2d 1555, 1562-63, 19 USPQ2d 1111 (Fed. Cir. 1991). See also MPEP 2163.04.
For a claim to a genus, a generic statement that defines a genus of substances by only their functional activity does not provide an adequate written description of the genus. Reagents of the University of California v. Eli Lilly, 43 USPQ2d 1398 (CAFC 1997). The recitation of a functional property alone, which must be shared by the members of the genus, is merely descriptive of what the members of the genus must be capable of doing, not of the substance and structure of the members. The Federal Circuit has cautioned that, for claims reciting a genus of antibodies with particular functional properties (e.g., high affinity, neutralization activity, competing with a reference antibody for binding), “[c]laiming antibodies with specific properties, e.g., an antibody that binds to human TNF-α with A2 specificity, can result in a claim that does not meet written description even if the human TNF-α protein is disclosed because antibodies with those properties have not been adequately described." Centocor Ortho Biotech Inc. v. Abbott Labs., 97 USPQ2d 1870, 1875, 1877-78 (Fed. Cir. 2011).
“[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.” Ariad, 598 F.3d at 1350 (quoting Eli Lilly, 119 F.3d at 1568-69). A “representative number of species” means that those species that are adequately described are representative of the entire genus. AbbVie Deutschland GMBH v. Janssen Biotech, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014) (“The ’128 and ’485 patents, however, only describe species of structurally similar antibodies that were derived from Joe-9. Although the number of the described species appears high quantitatively, the described species are all of the similar type and do not qualitatively represent other types of antibodies encompassed by the genus.”). 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. 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, 97 USPQ2d at 1875 (“[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.”). A chimeric antibody shares the full heavy and light chain variable regions with the corresponding mouse antibody; that is, the structure shared between a mouse and chimeric antibody would generally be expected to conserve the antigen binding activity.
Lastly, even if a selection procedure is disclosed that was, at the time of the invention, sufficient to enable the skilled artisan to identify antibodies with the recited functional properties, the written description provision of 35 U.S.C § 112 is severable from its enablement provision. Ariad, 94 USPQ2d at 1167; Centocor at 1876 (“The fact that a fully-human antibody could be made does not suffice to show that the inventors of the '775 patent possessed such an antibody.”)
The claims are rejected because the specification does not adequately describe all the species encompassed by the genus of antibodies (claims 138-140, 144-147 and 155), or genus of agents (claims 157-159).
(i) Claims 138-140 encompass a genus of antibodies defined solely by their binding epitopes.
Berglund et al. (Protein Science, 2008, 17:606-613) discloses that a linear epitope is comprised of 9-22 continuous amino acids on a protein (page 606, left column, lines 3-8) and a conformational epitope is comprised of stretches of several linear epitopes where at least one of the linear epitope is at least 4-7 residues in length (page 606, left column, lines 8-12 in particular). Certainly it is more difficult to fully characterize a conformational epitope to which an antibody binds than it is to characterize a linear epitope because residues of the antigen are contained by separated portions of the antigen that are only juxtaposed when the antigen occurs in its native, three-dimensional state. It is far more difficult to predict the structure and function of monoclonal antibodies that bind to a conformational epitope. The existence, number and structures of antibodies defined by their binding epitopes are not predictable. The specification does not purport to describe any correlation between a particular antibody structure and the claimed function of binding to a specific epitope. The prior art does not teach how to predict the structural features of the antibodies that bind to a disclosed epitope. These and other studies on antibody epitopes do not provide sufficient information for a skill artisan to predict the structural and functional properties of a genus of antibodies that bind to a particular epitope based on the disclosure of an antibody epitope or species of antibodies that bind to a particular epitope.
It appears that the specification only studies the binding epitope of three antibodies mAb1, mAb4 (urelumab) and mAB5 (utomilumab) (Example 5 and [0119]). Therefore, the written description is not commensurate in scope of the claims.
(ii) claims 144-147 and 155 encompass a genus of antibodies defined solely by function.
Claim 144 relates to an agonist antibody that bind human CD137, and exhibits at least one or more of the following properties relative to reference antibody urelumab:
(a) does not induce or enhance intrahepatic T cell activation;
(b) does not induce or enhance intrahepatic T cell proliferation;
(c) does not induce or enhance intrasplenic T cell activation;
(d) does not induce or enhance intrasplenic T cell proliferation;(e) does not induce or enhance macrophage activation;
(f) does not induce or enhance macrophage differentiation;
(g) does not induce or enhance alanine aminotransferase (ALT) activity; and
(h) any combination of properties (a) - (g).
Claim 145 relates to an agonist antibody that bind human CD137 and induces or enhances cytokine production of an immune cell in the subject,
Claim 146 further limit claim 145, wherein the cytokine produced is IL-2, TNFα, IL-13, IFN[Symbol font/0x67], or combinations thereof
Claim 147 further limit claim 145, wherein the immune cells express CD45.
Claim 155 relates to an agonist antibody that bind human CD137 and induces or enhances one or more of the following in a cancer cell:
(a) dimerization of CD137 trimers; (b) multimerization of CD137 trimers; (c) human CD137-mediated T cell activation; (d) human CD137-mediated cytotoxic T cell response; (e) human CD137-mediated T cell proliferation; and (f) human CD137-mediated cytokine production.
Claims 144-147 and 155 encompass a genus of anti-CD137 antibodies defined solely by function. For a claim to a genus, a generic statement that defines a genus of substances by only their functional activity does not provide an adequate written description of the genus. Reagents of the University of California v. Eli Lilly, 43 USPQ2d 1398 (CAFC 1997).
It appears that the specification discloses seven anti-human CD137 antibodies (mAb1, mAb7, mAb8, mAb9, mAb10, mAb11 and mAb12) (see Figures and working examples). Therefore, the written description is not commensurate in scope of the claims. The specification does not purport to describe any correlation between a particular antibody structure and the claimed functions. One cannot predict the structures of other antibodies of the genus from the disclosed seven antibodies. There is no reason to expect that the disclosed antibodies are either representative of the genus, or that they would share a common structure (e.g. same six CDRs). There is no antibody structure recited that would be expected to provide the claimed function.
Absent some indication of what antibody structures might fall within the claims, the claims are so broad as to encompass any anti-human CD137 antibodies having the recited function. However, without further testing one of ordinary skill in the art would not be able to envision the antibodies having the recited functions.
(iii) Claims 157-159 encompass a genus of agents that can bind MHC I.
However, the specification does not describe any agents by structure. The prior art discloses antibodies which can bind MHC I. Hanagiri et al. (J Surg Res. 2013, 181: e57-e63 teaches detecting HLA class I (human MHC class I) protein expressed by lung cancer cells by immunohistochemistry using an antibody (page e58, column 2). However, the antibodies are not representative number of species for the genus because the term “agent” encompasses non-antibody molecules, such as proteins, peptides, small molecule compounds, nucleic acids, etc. Therefore, the written description is not commensurate in scope of the claims. Furthermore, the specification does not purport to describe any correlation between a particular structure and the claimed function (binding to MHC I). One cannot envision the structures of the broadly encompassed agents.
Therefore, the skilled artisan would not recognize that applicants were in possession of the invention as broadly claimed at the time the application was filed.
It is noted that, “[r]egardless whether a compound is claimed per se or a method is claimed that entails the use of the compound, the inventor cannot lay claim to the subject matter unless he can provide a description of the compound sufficient to distinguish infringing compounds from non-infringing compounds, or infringing methods from non-infringing methods.” University of Rochester v. G.D. Searle Co., 69 USPQ2d 1886 1984 (CAFC 2004) (emphasis added).
Claim Rejections - 35 USC § 102
17. The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale or otherwise available to the public before the effective filing date of the claimed invention.
18. Claims 134-136, 138-147, 155-156 and 162 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Bobrowicz et al. (US 10,279,039B2, pub. date: 5/7/2019).
Note that the effective filing date of 134-147, 155-159 and 162 is 8/4/2023 (see paragraph 6 above).
Regarding claim 134, Bobrowicz et al. teaches a method of treating cancer in a subject, comprising administering to the subject an agonist monoclonal antibody, or antigen binding portion thereof, that specifically binds human CD137, thereby treating cancer in the subject (title and claims). All nucleated cells including cancer cells express MHC1.
Regarding claim 135, Bobrowicz et al. teaches that the antibody or antigen binding portion thereof comprises heavy and light chain variable regions comprising the amino acid sequences of SEQ ID NOs: 4 and 6, respectively (claims). The amino acid sequences of SEQ ID NOs: 4 and 6 are 100% identical to instant of SEQ ID NOs: 4 and 6, respectively,
Regarding claims 136 and 162, Bobrowicz et al. teaches that the antibody or antigen binding portion thereof comprises heavy and light chain variable regions comprising the amino acid sequences of SEQ ID NOs: 4 and 6, respectively (claims). SEQ ID NO:4 comprise heavy chain CDR1, CDR2 and CDR3 sequences of SEQ ID NOs: 48, 56 and 68, respectively. SEQ ID NO:6 comprises light chain CDR1, CDR2 and CDR3 sequences of SEQ ID NOs: 69, 78 and 89, respectively.
Regarding claims 138-140, Bobrowicz teaches that the anti-CD137 antibody binds to the epitope defined in instant claims 138-140 (column 4).
Regarding claim 141, Bobrowicz teaches that the anti-CD137 antibody is IgG1 or IgG4 (claims).
Regarding claim 142, Bobrowicz teaches that the cancer is melanoma (column 115, line 40).
Regarding claim 143, Bobrowicz teaches that the anti-CD137 is IgG1 or IgG4 (claims), which can bind Fc gamma receptor.
Regarding claims 144-147 and 155, Bobrowicz teaches that the anti-CD137 antibody has all the functions recited in these claims (columns 16 and 21).
Regarding claim 156, Bobrowicz teaches that the anti-CD137 antibody comprises SEQ ID NO:129 and 130 (claim 10). The amino acid sequences of SEQ ID NOs: 129 and 130 are 100% identical to instant of SEQ ID NOs: 129 and 130, respectively.
19. Claims 134, 141-147 and 155 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Clinical Trial NCT00612664 (pub. date: 10/12/2015), as evidenced by Chester et al. (J Clin Oncol., 2014, 32(15 suppl), page 3017, IDS filed on 10/31/2023).
Regarding claims 134 and 142, Clinical Trial NCT00612664 teaches a method of treating melanoma in a subject, comprising administering to the subject a therapeutically effective amount of BMS-663513 (also known as urelumab, an agonistic anti-CD137 antibody that binds to human CD137). All nucleated cells including melanoma cancer cells express MHC1.
Regarding claims 141 and 143, urelumab is an IgG4 antibody, which can bind a Fc gamma receptor.
Regarding claim 144-147 and 155, urelumab binds human CD137 and inherently exhibits all the recited functions, as evidenced by the instant specification (see working examples, [0688], [00675], and drawings, mAb4 is urelumab ([0016]), page 180, Example 22) and Chester.
Chester et al. disclose that urelumab, a fully human anti-CD137 antibody is capable of binding to human CD-137, treating a cancer, inducing or enhancing T cell activation, inducing or enhancing a cytotoxic T cell response, inducing or enhancing T cell proliferation, inducing or enhancing cytokine production (see abstract).
Claim Rejections - 35 USC § 103
20. 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.
21. Claims 134-147, 155-159 and 162 are rejected under 35 U.S.C. 103 as being unpatentable over Bobrowicz et al. (US 10,279,039B2, pub. date: 5/7/2019), in view of Haworth et al. (Pdeiatr Blood Cancer, 2015, 62(4): 571-576) and Hanagiri et al. (J Surg Res. 2013, 181: e57-e63).
The teaching of Bobrowicz et al. have been set forth above as they apply to claims 134-136, 138-147, 155-156 and 162.
Regarding claims 137 and 157-159, Bobrowicz et al. does not teach detecting MHC I protein in a biological sample comprising cancer cells from the subject with an agent that binds MHC1. However, these deficiencies are made up for in the teachings of Haworth and Hanagiri.
Haworth et al. teaches tumor cell expression of MHC Class I has emerged as a potential determinant of the therapeutic success of many immunotherapy approaches (abstract). MHC class I is expressed by all nucleated cells and, together with the beta-2-microglobulin chain, functions to display short peptide antigens derived from either intracellular pathogens or endogenous self-antigens (page 2). The immunologic executioners ultimately resulting from MHC peptide presentation are cytotoxic T lymphocytes (CTLs, CD8+) for the adaptive immune response and natural killer (NK) cells for the innate immune response (page 2). CTLs require tumor antigen presentation on the target cell by MHC Class I molecules to delineate self from non-self (page 2). One of the most common means by which tumors evade the host immune response is by down-regulation of MHC Class I molecule expression, thereby rendering any endogenous or therapeutic anti-tumor T cell responses ineffective (page 2).
Hanagiri et al. teaches detecting HLA class I (human MHC class I) protein expressed by non-small cell lung cells by immunohistochemistry using an antibody in (page e58, column 2).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the invention to have modified the method of Bobrowicz to detect MHC class I protein on tumor cells before administering the anti-CD137 antibody in view of Haworth. One of ordinary skill in the art would have been motivated to because Haworth teaches that tumor cell expression of MHC Class I has emerged as a potential determinant of the therapeutic success of many immunotherapy approaches (abstract), and CTLs require tumor antigen presentation on the target cell by MHC Class I molecules to delineate self from non-self and to kill tumor cells (page 2). One of ordinary skill in the art would have a reasonable expectation of success because methods of detecting MHC I were known in the art as shown by Hanagiri.
22. Claims 134, 137, 141-147, 155 and 157-159 are rejected under 35 U.S.C. 103 as being unpatentable over Clinical Trial NCT00612664 (pub. date: 10/12/2015), as evidenced by Chester et al. (J Clin Oncol., 2014, 32(15 suppl), page 3017, IDS filed on 10/31/2023), in view of Haworth et al. (Pdeiatr Blood Cancer, 2015, 62(4): 571-576) and Hanagiri et al. (J Surg Res. 2013, 181: e57-e63).
The teaching of Clinical Trial NCT00612664 have been set forth above as they apply to claims 134, 141-147 and 155.
Regarding claims 137 and 157-159, Clinical Trial NCT00612664 does not teach detecting MHC I protein in a biological sample comprising cancer cells from the subject with an agent that binds MHC1. However, these deficiencies are made up for in the teachings of Haworth and Hanagiri.
The teachings of Haworth and Hanagiri have been discussed above.
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the invention to have modified the method of Clinical Trial NCT00612664 to detect MHC 1 on tumor cells before administering the anti-CD137 antibody in view of Haworth. One of ordinary skill in the art would have been motivated to because Haworth teaches that tumor cell expression of MHC Class I has emerged as a potential determinant of the therapeutic success of many immunotherapy approaches (abstract), and CTLs require tumor antigen presentation on the target cell by MHC Class I molecules to delineate self from non-self and to kill tumor cells (page 2). One of ordinary skill in the art would have a reasonable expectation of success because methods of detecting MHC I were known in the art as shown by Hanagiri.
Double Patenting
23. 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 §§ 706.02(l)(1) - 706.02(l)(3) 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 USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The 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/process/file/efs/guidance/eTD-info-I.jsp.
24. Claims 134-147, 155-159 and 161-162 are rejected on the ground of nonstatutory double patenting as being unpatentable over
(i) claims 1-20 of U.S. Patent No. 10,279,039,
(ii) claims 1-20 of U.S. Patent No. 10,279,040,
(iii) claims 1-11 of U.S. Patent No. 11,851,497, or
(iv) claims 1-22 of U.S. Patent No. 12,286,483,
in view of Haworth et al. (Pdeiatr Blood Cancer, 2015, 62(4): 571-576) and Hanagiri et al. (J Surg Res. 2013, 181: e57-e63).
The claims of each patent disclose (a) a method of treating cancer in a subject, comprising administering to the subject an isolated monoclonal antibody, or antigen binding portion thereof, that specifically binds human CD137, wherein the antibody or antigen binding portion thereof comprises heavy and light chain variable regions comprising the amino acid sequences of SEQ ID NOs: 4 and 6, respectively, thereby treating cancer in the subject, wherein the antibody or antigen binding portion thereof comprises an IgG1 or IgG4 heavy chain constant region; and (b) a method of treating cancer in a subject, comprising administering to the subject an isolated monoclonal antibody that specifically binds human CD137, wherein the antibody comprises heavy and light chains comprising the amino acid sequences of SEQ ID NOs: 129 and 133, respectively, wherein the antibodies have all the properties recited in the instant claims, e.g. inducing or enhancing least one cytokine selected from the group consisting of IL-2, TNFα, IL-13, IFN[Symbol font/0x67], or combinations thereof. The amino acid sequences of SEQ ID NOs: 4, 6, 129 and 133 are 100% identical to instant SEQ ID NOs: 4, 6, 129 and 133, respectively. All nucleated cells including melanoma cancer cells express MHC1.
The claims of each patent do not disclose detecting MHC I protein in a biological sample comprising cancer cells from the subject with an agent that binds MHC1.
However, these deficiencies are made up for in the teachings of Haworth and Hanagiri.
The teachings of Haworth and Hanagiri have been discussed above.
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the invention to have modified the method of each patent to detect MHC 1 on tumor cells before administering the anti-CD137 antibody in view of Haworth. One of ordinary skill in the art would have been motivated to because Haworth teaches that tumor cell expression of MHC Class I has emerged as a potential determinant of the therapeutic success of many immunotherapy approaches (abstract), and CTLs require tumor antigen presentation on the target cell by MHC Class I molecules to delineate self from non-self and to kill tumor cells. One of ordinary skill in the art would have a reasonable expectation of success because methods of detecting MHC I were known in the art as shown by Hanagiri.
25. Claims 134-147, 155, 157-159 and 161-162 are rejected on the ground of nonstatutory double patenting as being unpatentable over
(i) claims 1-20 of U.S. Patent No. 10,434,175, or
(ii) claims 1-28 of U.S. Patent No. 11,718,679,
in view of Haworth et al. (Pdeiatr Blood Cancer, 2015, 62(4): 571-576) and Hanagiri et al. (J Surg Res. 2013, 181: e57-e63).
The claims of each patent disclose a method of treating cancer in a subject comprising administering to the subject an isolated monoclonal antibody, or antigen binding portion thereof, that specifically binds human CD137, wherein the antibody or antigen binding portion thereof comprises three CDRs (CDR1, CDR2 and CDR3) of the light chain variable region set forth in SEQ ID NO: 6, and three CDRs (CDR1, CDR2 and CDR3) of the heavy chain variable region set forth in SEQ ID NO: 4, thereby treating cancer in the subject, wherein the antibody comprises an IgG1 or an IgG4 heavy chain constant region, wherein the antibodies have all the recited functions. The amino acid sequences of SEQ ID NOs: 4 and 6 are 100% identical to instant SEQ ID NOs: 4 and 6, respectively. All nucleated cells including melanoma cancer cells express MHC1.
The claims of the patent do not disclose detecting MHC I protein in a biological sample comprising cancer cells from the subject with an agent that binds MHC1. However, these deficiencies are made up for in the teachings of Haworth and Hanagiri.
The teachings of Haworth and Hanagiri have been discussed above.
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the invention to have modified the method of each patent to detect MHC 1 on tumor cells before administering the anti-CD137 antibody in view of Haworth. One of ordinary skill in the art would have been motivated to because Haworth teaches that tumor cell expression of MHC Class I has emerged as a potential determinant of the therapeutic success of many immunotherapy approaches (abstract), and CTLs require tumor antigen presentation on the target cell by MHC Class I molecules to delineate self from non-self and to kill tumor cells. One of ordinary skill in the art would have a reasonable expectation of success because methods of detecting MHC I were known in the art as shown by Hanagiri.
26. Claims 134-147, 155-159 and 161-162 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 150-171 of copending Application Nol 19/082,688, in view of Haworth et al. (Pdeiatr Blood Cancer, 2015, 62(4): 571-576) and Hanagiri et al. (J Surg Res. 2013, 181: e57-e63).
This is a provisional nonstatutory double patenting rejection.
The claims of the copending application disclose a method of treating cancer in a subject comprising administering to the subject an isolated monoclonal antibody, or antigen binding portion thereof, that specifically binds human CD137, wherein the antibody or antigen binding portion thereof comprises three CDRs (CDR1, CDR2 and CDR3) of the light chain variable region set forth in SEQ ID NO: 6, and three CDRs (CDR1, CDR2 and CDR3) of the heavy chain variable region set forth in SEQ ID NO: 4, thereby treating cancer in the subject, and (b) a method of treating cancer in a subject, comprising administering to the subject an isolated monoclonal antibody that specifically binds human CD137, wherein the antibody comprises heavy and light chains comprising the amino acid sequences of SEQ ID NOs: 129 and 133, respectively, wherein the antibodies have all the recited function, wherein the antibodies have all the recited functions. The amino acid sequences of SEQ ID NOs: 4, 6, 129 and 133 are 100% identical to instant SEQ ID NOs: 4, 6, 129 and 133, respectively. All nucleated cells including melanoma cancer cells express MHC1.
The claims of the copending application do not disclose detecting MHC I protein in a biological sample comprising cancer cells from the subject with an agent that binds MHC1. However, these deficiencies are made up for in the teachings of Haworth and Hanagiri.
The teachings of Haworth and Hanagiri have been discussed above.
It would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made to have modified the method of the copending application to detect MHC 1 on tumor cells before administering the anti-CD137 antibody in view of Haworth. One of ordinary skill in the art would have been motivated to because Haworth teaches that tumor cell expression of MHC Class I has emerged as a potential determinant of the therapeutic success of many immunotherapy approaches (abstract), and CTLs require tumor antigen presentation on the target cell by MHC Class I molecules to delineate self from non-self (page 2). One of ordinary skill in the art would have a reasonable expectation of success because methods of detecting MHC I were known in the art as shown by Hanagiri.
27. Claims 134-147, 155, 157-159 and 161-162 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 4, 19, 69, 71, 79-80 and 90 of copending Application Nol 17/423,599, in view of Haworth et al. (Pdeiatr Blood Cancer, 2015, 62(4): 571-576) and Hanagiri et al. (J Surg Res. 2013, 181: e57-e63).
This is a provisional nonstatutory double patenting rejection.
The claims of the copending application disclose a method of treating cancer in a subject comprising administering to the subject an isolated monoclonal antibody, or antigen binding portion thereof, that specifically binds human CD137, wherein the antibody or antigen binding portion thereof comprises three CDRs (CDR1, CDR2 and CDR3) of the light chain variable region set forth in SEQ ID NO: 6, and three CDRs (CDR1, CDR2 and CDR3) of the heavy chain variable region set forth in SEQ ID NO: 4, thereby treating cancer in the subject. The amino acid sequences of SEQ ID NOs: 4 and 6 are 100% identical to instant SEQ ID NOs: 4 and 6, respectively. The antibodies would inherently have all the recited functions. All nucleated cells including melanoma cancer cells express MHC1.
The claims of the copending application do not disclose MHC I protein in a biological sample comprising cancer cells from the subject with an agent that binds MHC1. However, these deficiencies are made up for in the teachings of Haworth and Hanagiri.
The teachings of Haworth and Hanagiri have been discussed above.
It would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made to have modified the method of the copending application to detect MHC 1 on tumor cells before administering the anti-CD137 antibody in view of Haworth. One of ordinary skill in the art would have been motivated to because Haworth teaches that tumor cell expression of MHC Class I has emerged as a potential determinant of the therapeutic success of many immunotherapy approaches (abstract), and CTLs require tumor antigen presentation on the target cell by MHC Class I molecules to delineate self from non-self (page 2). One of ordinary skill in the art would have a reasonable expectation of success because methods of detecting MHC I were known in the art as shown by Hanagiri.
Conclusion
28. No claims are allowed.
29. Any inquiry concerning this communication or earlier communications from the examiner should be directed to HONG SANG whose telephone number is (571)272-8145. The examiner can normally be reached on Monday-Friday 8am-5pm.
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/HONG SANG/Primary Examiner, Art Unit 1643
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