DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Status of Claims
Claims 13-16, 18-29 and 31-38 are pending.
Claims 15, 18-23, 28 and 31-36 are amended.
Claims 13-16, 18-29 and 31-38 are currently under consideration.
Priority
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. The U.S. effective filing date of all claims under examination is set at 08/18/2021 based on the provisional application 63/234,619 (filed 08/18/2021).
Information Disclosure Statement
The information disclosure statements (IDS) submitted are being considered by the examiner.
Claim Objections
Claims 13, 14, 19, 21, 24, 25, 26 and 27 are objected to because of the following informalities:
Claims 13, 14, 21, 24, 25, 26 and 27 recite the limitation “APP polypeptides". It is suggested that the claims be amended to include the full form for the abbreviation of “APP”. The instant specification discloses in Table 3 the phrase “Antigen processing and presentation gene set”. Thus, the Examiner has taken APP to mean “antigen processing and presentation” for purposes of examination.
Claim 19 appears to contain a typographical error. The term “mb” should be amended to “Mb” to represent megabases.
Appropriate correction is required.
Claim Rejections 35 U.S.C.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 13-16, 18-20, 22-29 , 31-33, and 35-38 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.
In the instant case, the claims are inclusive of a genus of APP (antigen processing and presentation) polypeptides. However, the written description in this case only sets forth thirty-one APP polypeptides, namely: PYCARD, HFE , HLA-DOA , HLA-DOB , TREM2 , TAPBPL , HLA-A, HLA-B, HLA-C, HLA-E, HLA-F, HLA-G, HLA-H, AZGP1, B2M, TAP2, ABCB9, IDE, ERAP1, ERAP2, TAP1, TAPBP, AP3B1, AP3D1, CD1A, CD1B, CD1C, CD1D, CD1E, ATG5, and CD74, as members of the genus (Pg 3 lines 20-28). Therefore, only thirty-one APP polypeptides were disclosed as those associated with mesothelioma. The specification does not disclose, and the art does not teach, the genus of APP polypeptides as broadly as is encompassed in the claims.
A description of a genus may be achieved by means of a recitation of a representative number of species falling within the scope of the genus or by describing structural features common to that genus that “constitute a substantial portion of the genus.” See University of California v. Eli Lilly and Co., 119 F.3d 1559, 1568, 43 USPQ2d 1398, 1406 (Fed. Cir. 1997): “A description of a genus of cDNAs may be achieved by means of a recitation of a representative number of cDNA, defined by nucleotide sequence, falling within the scope of the genus or of a recitation of structural features common to the members of the genus, which features constitute a substantial portion of the genus.” The inventions at issue in Lilly were DNA constructs per se, the holdings of that case is also applicable to claims such as those at issue here.
Further, disclosure that does not adequately describe a product itself logically cannot adequately describe a method of using that product. See Ariad, 598 F.3d at 1354-55 (“Regardless whether the asserted claims recite a compound, Ariad still must describe some way of performing the claimed methods... the specification must demonstrate that Ariad possessed the claimed methods by sufficiently disclosing molecules capable of reducing NF-kB activity so as to ‘satisfy the inventor' s obligation to disclose the technologic knowledge upon which the patent is based, and to demonstrate that the patentee was in possession of the invention that is claimed.' ”) (internal citation omitted); see also Univ. of Rochester v. G.D. Searle& Co., Inc., 358 F.3d916,918 (Fed.Cir.2004) (applying the same analysis to assess written description for claims to a “method for selectively inhibiting” a particular enzyme by administering a functionally defined compound, i.e., a “non-steroidal compound that selectively inhibits activity” of the gene product for that enzyme).
Regarding claims to a product defined by function, without a correlation between structure and function, the claim does little more than define the claimed invention by function. That is not sufficient to satisfy the written description requirement. See Eli Lilly, 119 at1568 USPQ2d at 1406 (“definition by function…does not suffice to define the genus because it is only an indication of what the gene does, rather than what it is”).
The instant specification fails to provide sufficient descriptive information, such as definitive structural features that are common to the genus. That is, the specification provides neither a representative number of species APP polypeptides associated with mesothelioma that encompass the genus nor does it provide a description of structural features that are common to the genus so that one of skill in the art can ‘visualize or recognize’ the members of the genus. “[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.
Since the disclosure fails to describe common attributes or characteristics that adequately identify members of the genus, and because the genus is highly variant, the disclosure of thirty-one species found in the specification for APP polypeptides associated with mesothelioma is insufficient to describe the genus. Thus, one of skill in the art would reasonably conclude that the disclosure fails to provide a representative number of species to describe the genus as broadly claimed.
Vas-Cath Inc. v. Mahurkar, 19USPQ2d 1111, clearly states “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). As discussed above, even though Applicant may propose methods of screening for possible members of the genus, the skilled artisan cannot envision the detailed chemical structure of the encompassed genus, and therefore conception is not achieved until reduction to practice has occurred, regardless of the complexity or simplicity of the method of isolation. Adequate written description requires more than a mere statement that it is part of the invention and reference to a potential method of isolation. The compound itself is required. See Fiers v. Revel, 25 USPQ2d 1601 at 1606 (CAFC 1993) and Amgen Inc. v. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016. See Ariad, 94 USPQ2d at 1161; 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.”)
One cannot describe what one has not conceived. See Fiddes v. Baird, 30 USPQ2d 1481 at 1483. In Fiddes, claims directed to mammalian FGF’s were found to be unpatentable due to lack of written description for that broad class. The specification provided only the bovine sequence. 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).
Claim Rejections - 35 USC § 103 (First)
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 13-16, 18-20, 22-25 are rejected under 35 U.S.C. 103(a) as being unpatentable over Lee et al. (JCI Insight. 2018;3(7):e98575; Pg 1-14) in view of Mansfield et al. (Journal of Thoracic Oncology, Volume 14, Issue 2, 2019, Pages 276-287).
For the purposes of examination and search for prior art, the term “junction” in the instant claims has been interpretated as including location or the point of the break of any type of chromosomal rearrangement including insertions, deletions, translocations and inversions (paragraph [0029] instant specification). The phrase “high junction burden” has been interpretated to include instances where a chromosome comprises a high number of said breaks due to said chromosomal rearrangements.
Lee et al. teaches analysis of the immunologic cellular networks within human malignant pleural mesothelioma (MPM) using mass cytometry (Abstract and Figure 1). They teach that TiME-I tumors contained more high-abundance neoantigens with concordant high expression of their specific MHC-I proteins and/or MHC-II proteins, such as HLA-A*01:01, HLA-A*30:02, HLA-B*18:01 and HLA-DRB1 (Figures 3B and 3D, Supplemental Figures 8 and 9 and Pg 5 first full paragraph lines 3-8) – which are “APP polypeptides”. The examiner takes official notice that one of skill in the art would recognize that there are at least six known proteins that are MHC-I and/or MHC-II that present neoantigens. Lee et al. further teaches that human patients whose tumors demonstrated a good-TiME signature had statistically improved and dramatic responses to PD-1 inhibition using the PD-1 inhibitor nivolumab at 8 months after treatment (Figure 5, see specifically 5C and 5D, Pg 7 lines 7-9 and Supplemental Figure 12). Note that good-TiME is synonymous with TiME-I (see Pg 5 second full paragraph, last two lines).
Lee et al also teaches that twelve human MPM patients underwent complete resection without preoperative treatment wherein their tumor samples were used to perform mass cytometry, MS, and mRNA microarray studies (Figure 2 mass cytometry (CyTOF); Figure 3 mass spectrometry; Figure 4A mRNA differential expression; Pg 10 first full paragraph lines 2-5). They teach that based on the TiME signature of 10 MPM patients with advanced and unresectable MPM, the patients were treated with anti–PD-1 therapy after they had progressed after treatment with a platinum-based agent and pemetrexed (Pg 10 first full paragraph lines 5-7).
Lee et al. does not specifically teach mesothelioma that comprises high junction burden.
However, these deficiencies are made up in the teachings of Mansfield et al.
Mansfield et al. teaches that MPM is not associated with high tumor mutation burden as with other carcinogen-related tumors but was observed to have inter- or intrachromosomal rearrangements in every specimen studied and were frequently in a pattern of chromoanagenesis (Abstract, Table 1 and Figure 1). They teach that said structural chromosomal rearrangements potentially drive unique neoantigen expression in MPM (Abstract and Figure 1). They also teach using mate-pair sequencing (MPseq) which tils the whole genome with 2 to 5 kb fragments to reliably detect structural variants of insertions, deletions, and rearrangements where the method detected a range of between 3 to 298 junctions or genomic rearrangements 22 studied specimens (Pg 277 column left second paragraph and Table 1). They further teach the genome plot for a single specimen (ME022) and illustrated the detected intrachromosomal and interchromosomal rearrangements, in particular where chromosome 7 was detected to have high numbers of said rearrangements (Figure 2; see reproduction below).
Figure 2 of Mansfield et al.
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Mansfield et al. also teaches that chromosomal insertions and deletions (indel) that result from frameshifts were predictive of response to PD-1 inhibition in separate cohorts of patients with melanoma and therefore suggest that chromosomal rearrangement-related peptides with neoantigenic potential that their method detected may promote immunogenicity of MPM in a similar fashion as frameshift indel high neoantigens, and as such be equally responsive to PD-1 inhibition (Pg 286 column left paragraph spanning lines 16-26).
One of ordinary skill in the art would have been motivated, with a reasonable expectation of success, to perform a combined method of treating a human having mesothelioma comprising (a) determining that mesothelioma cells contain the presence of an elevated level of just any number of polypeptides involved in antigen processing and presentation of Lee et al. (which are “APP polypeptides” and a high level of chromosomal rearrangements of Mansfield et al.; and (b) administering, nivolumab, an immune checkpoint inhibitor as taught by Lee et al. because Lee et al. teaches that detection and quantification of the abundant potential neoantigens in MPM tumors and quantification of high protein expression of their corresponding MHC-I and MHC-II HLA proteins underlies the strongest clinical responses to immune checkpoint inhibitors and highlights the importance of both neoantigen abundance and neoantigen presentation in clinical responses to these agents (Pg 9 third paragraph 12-16) and Mansfield et al. teaches that the presence of junction-related or chromosomal rearrangement-related neoantigens in MPM provide favorable responses to immune checkpoint inhibitors (Pg 286 column left paragraph spanning lines 16-26). This is an example of (A) Combining prior art elements according to known methods to yield predictable results; and (G) Some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention. See MPEP 2143. Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art, absent unexpected results.
It would have been obvious to perform a combined method of treating a mammal having mesothelioma comprising determining that the mesothelioma cells contain the presence of polypeptides involved in antigen processing and presentation (including those of Lee et al). (which includes “at least 6 APP polypeptides”) because higher numbers of such polypeptides present in the cells correlate with predictable “sensitivity” of the tumor to the administered immune checkpoint inhibitor.
Regarding instant claim 19, it would have been obvious to perform a combined method of treating a human having mesothelioma as taught by Lee et al. and Mansfield above, wherein the mesothelioma comprising a high junction burden comprises at least 17 junctions per Mb because Mansfield et al. teaches that there was a significantly high number of junctions detected on chromosome 7 (see Figure 2 of Mansfield et al. reproduced above). It is known that chromosome 7 is approximately 160 Mb and as such, from Figure 2 of Mansfield et al. it can be inferred or extrapolated that the number of junctions (depicted by the number of lines extending out from chromosome 7) that are within a 1Mb length could easily be at least 17.
With regards to instant claim 35, it would have been obvious to perform the above combined method of treating mesothelioma with a cancer treatment that is not an immune checkpoint inhibitor which comprises a platinum-based agent and pemetrexed as taught by Lee et al. because Lee et al. teaches that this is a standard chemotherapy treatment for MPM in accordance with current National Comprehensive Cancer Network guidelines (Pg 7 lines 4-5).
With regards to instant claim 36, it would have been obvious to perform the above combined method of treating mesothelioma with a cancer treatment that is not an immune checkpoint inhibitor which comprises surgery or radiation therapy as taught by Lee et al. because Lee et al. teaches that in patients with early-stage disease, surgery-based multimodal approaches incorporating cytotoxic chemotherapy and/or radiotherapy may improve median survival to 26 months (Pg 1 lines 4-5).
Claim Rejections - 35 USC § 103 (Second)
Claims 13-16, 18-20, 21, 22-25 are rejected under 35 U.S.C. 103(a) as being unpatentable over Lee et al. (JCI Insight. 2018;3(7):e98575; Pg 1-14) and Mansfield et al. (Journal of Thoracic Oncology, Volume 14, Issue 2, 2019, Pages 276-287) as applied to claims 13-16, 18-20, 22-29, 31-33 and 35-38 above, and further in view of Cheng et al. (Front. Immunol. 12:646523; 16 February 2021; Pg 1-21), Creaney et al. (Cancer Genomics & Proteomics 14: 103-118; 2017) and Otterstrom et al. (British Journal of Cancer volume 110, pages2040–2046; 2014).
The combined teachings of Lee et al. and Mansfield et al. have already rendered claims 13-16, 18-20, 22-29, 31-33 and 35-38 obvious as described in the first 103 rejection above.
Lee et al. and Mansfield et al. do not specifically teach APP polypeptides that are TREM2, B2M, or CD74.
However, these deficiencies are made up in the teachings of Cheng et al., Creaney et al. and Otterstrom et al.
Cheng et al. teaches that TREM2 is an immunological and prognostic biomarker in cancers (Title and Abstract). They teach that TREM2 expression significantly correlated with tumor stage in mesothelioma (Pg 8 column left second full paragraph lines 2-4 and Supplementary Figure 1). They also teach that TREM2 plays an essential role in cancer immunity and that checkpoint immunotherapy can be improved by TREM2 functioning to modify tumor myeloid infiltrates (Pg 19 column left first full paragraph lines 17-18).
Creaney et al. teaches the proteomic analysis of malignant mesothelioma (MM) secretome where expression of B2MG is found to be up-regulated (Abstract and Table II). They teach that B2MG is a component of the major histocompatibility complex class I molecule and acts as a signal transducing molecule that is implicated in cancer growth and metastasis (Pg 114 column left spanning paragraph lines 7-9).
Otterstrom et al. teaches that CD74 overexpression in tumour cells is a molecular trait found in 98% of MPM (Pg 2044 column left first full paragraph lines 3-4 and Table 2). They teach that patients with higher CD74 expression levels correlated with longer OS (Abstract and Pg 2042 column right second paragraph lines 1-5).
One of ordinary skill in the art would have been motivated, with a reasonable expectation of success, to perform the combined method of treating a human having mesothelioma as taught by Lee et al. and Mansfield et al. and combine it with determining the presence of TREM2 as taught by Cheng et al., B2MG as taught by Creaney et al. and CD74 as taught by Otterstrom et al. because the expression of said proteins are elevated in MPM or MM as taught by Cheng et al., Creaney et al. and Otterstrom et al. respectively, and because Cheng et al. teaches that TREM2 plays a role in improving checkpoint immunotherapy, Creaney et al. teaches that B2MG is a component of the MHC-I molecule and Otterstrom et al. teaches that CD74 is a good prognostic biomarker for MPM. Therefore, detecting the levels of these proteins can help tailor the choice of cancer treatment to the patient for effective treatment of mesothelioma. This is an example of (A) Combining prior art elements according to known methods to yield predictable results; and (G) Some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention. See MPEP 2143. Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art, absent unexpected results.
Claim Rejections - 35 USC § 103 (Third)
Claims 26-29, 31-33, 35 and 37-38 are rejected under 35 U.S.C. 103(a) as being unpatentable over Lee et al. (JCI Insight. 2018;3(7):e98575; Pg 1-14) in view of Mansfield et al. (Journal of Thoracic Oncology, Volume 14, Issue 2, 2019, Pages 276-287) and Otsuka et al. (Lung Cancer Volume 146, August 2020, Pages 86-96).
The teachings of Lee et al. and Mansfield et al. have been described in the first 103 rejection above.
Lee et al. and Mansfield et al. do not specifically teach a method for treating a mammal having mesothelioma comprising high junction burden but is determined to be absent of an elevated level of polypeptides expressed by at least 6 APP, and administering a cancer treatment that is not an immune checkpoint inhibitor.
However, these deficiencies are made up in the teachings of Otsuka et al.
Otsuka et al. teaches the treatment of MPM using a combination of chemotherapeutic agents of cisplatin (CDDP) and pemetrexed (PEM), and further in combination with anti-PD-1 antibody (Abstract and Fig. 3). They teach that treatment with chemotherapeutic agents or anti-PD-1 antibody inhibited tumor growth to some extent compared to the control group, whereas combination therapy significantly suppressed tumor growth compared to single treatment with each agent alone (Fig. 3B and Pg 88 right column paragraph spanning lines 3-7). They also teach that combined therapy CDDP+PEM and anti-PD-1 antibody significantly enhanced the antitumor effects by decreasing numbers of intratumoral myeloid-derived suppressor cells (MDSCs) and vessels likely through suppression of VEGF expression by CDDP + PEM (Fig. 5E and Pg 8 right column third full paragraph).
One of ordinary skill in the art would have been motivated, with a reasonable expectation of success, to perform a combined method of treating a mammal having mesothelioma comprising a high level of chromosomal rearrangements as taught by Mansfield et al. and determining that the mesothelioma sample contains the absence of an elevated level of several polypeptides involved in antigen processing and presentation using the techniques as taught by Lee et al., and administering CDDP+PEM in combination with an anti-PD-1 antibody as taught by Otsuka et al. because Ostuka et al. teaches that this chemotherapy and immunotherapy combination provided significantly enhanced antitumor compared to the chemotherapy or immunotherapy alone, and Mansfield et al. teaches that the presence of junction-related or chromosomal rearrangement-related neoantigens in MPM provide favorable responses to immune checkpoint inhibitors (Pg 286 column left paragraph spanning lines 16-26), and further Lee et al. teaches that platinum-based agents and pemetrexed are standard chemotherapy treatments for MPM in accordance with current National Comprehensive Cancer Network guidelines (Pg 7 lines 4-5). This is an example of (A) Combining prior art elements according to known methods to yield predictable results; and (G) Some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention. See MPEP 2143. Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art, absent unexpected results.
Claim Rejections - 35 USC § 103 (Fourth)
Claims 26-29, 31-33, 34, 35 and 37-38 are rejected under 35 U.S.C. 103(a) as being unpatentable over Lee et al. (JCI Insight. 2018;3(7):e98575; Pg 1-14), Mansfield et al. (Journal of Thoracic Oncology, Volume 14, Issue 2, 2019, Pages 276-287) and Otsuka et al. (Lung Cancer Volume 146, August 2020, Pages 86-96) as applied to claims 26-29, 31-33, 35 and 37-38 above and further in view of Cheng et al. (Front. Immunol. 12:646523; 16 February 2021; Pg 1-21), Creaney et al. (Cancer Genomics & Proteomics 14: 103-118; 2017) and Otterstrom et al. (British Journal of Cancer volume 110, pages2040–2046; 2014).
The combined teachings of Lee et al., Mansfield et al. and Otsuka et al. have already been described in the third 103 rejection above.
Lee et al., Mansfield et al. and Otsuka et al. do not specifically teach APP polypeptides that are TREM2, B2M, or CD74.
However, these deficiencies are made up in the teachings of Cheng et al., Creaney et al. and Otterstrom et al.
Cheng et al. teaches that TREM2 is an immunological and prognostic biomarker in cancers (Title and Abstract). They teach that TREM2 expression significantly correlated with tumor stage in mesothelioma (Pg 8 column left second full paragraph lines 2-4 and Supplementary Figure 1). They also teach that TREM2 plays an essential role in cancer immunity and that checkpoint immunotherapy can be improved by TREM2 functioning to modify tumor myeloid infiltrates (Pg 19 column left first full paragraph lines 17-18).
Creaney et al. teaches the proteomic analysis of malignant mesothelioma (MM) secretome where expression of B2MG is found to be up-regulated (Abstract and Table II). They teach that B2MG is a component of the major histocompatibility complex class I molecule and acts as a signal transducing molecule that is implicated in cancer growth and metastasis (Pg 114 column left spanning paragraph lines 7-9).
Otterstrom et al. teaches that CD74 overexpression in tumour cells is a molecular trait found in 98% of MPM (Pg 2044 column left first full paragraph lines 3-4 and Table 2). They teach that patients with higher CD74 expression levels correlated with longer OS (Abstract and Pg 2042 column right second paragraph lines 1-5).
One of ordinary skill in the art would have been motivated, with a reasonable expectation of success, to perform a combined method of treating a mammal having mesothelioma comprising a high level of chromosomal rearrangements as taught by Mansfield et al. and determining that the mesothelioma sample contains the absence of an elevated level of several polypeptides involved in antigen processing and presentation using the techniques as taught by Lee et al., and administering CDDP+PEM in combination with an anti-PD-1 antibody as taught by Otsuka et al., and combine it with determining the absence of TREM2 as taught by Cheng et al., B2MG as taught by Creaney et al. and CD74 as taught by Otterstrom et al. because the expression of said proteins are elevated in MPM or MM as taught by Cheng et al., Creaney et al. and Otterstrom et al. respectively, and because Cheng et al. teaches that TREM2 plays a role in improving checkpoint immunotherapy, Creaney et al. teaches that B2MG is a component of the MHC-I molecule and Otterstrom et al. teaches that CD74 is a good prognostic biomarker for MPM. Therefore, detecting the absence of these proteins can help tailor the choice of cancer treatment to the patient for effective treatment of mesothelioma. In addition, because Ostuka et al. teaches that chemotherapy and immunotherapy combination provided significantly enhanced antitumor compared to the chemotherapy or immunotherapy alone, and Mansfield et al. teaches that the presence of junction-related or chromosomal rearrangement-related neoantigens in MPM provide favorable responses to immune checkpoint inhibitors (Pg 286 column left paragraph spanning lines 16-26).
Claim Rejections - 35 USC § 103 (Fifth)
Claims 26 and 36 are rejected under 35 U.S.C. 103(a) as being unpatentable over Lee et al. (JCI Insight. 2018;3(7):e98575; Pg 1-14), Mansfield et al. (Journal of Thoracic Oncology, Volume 14, Issue 2, 2019, Pages 276-287) and Otsuka et al. (Lung Cancer Volume 146, August 2020, Pages 86-96) as applied to claims 26-29, 31-33, 35 and 37-38 above and further in view of Shah et al. (Clinical Lung Cancer Volume 22, Issue 2; March 2021; Pages: 142-146).
The teachings of Lee et al., Mansfield et al. and Otsuka et al. have been described in the third 103 rejection above.
Lee et al., Mansfield et al. and Otsuka et al. do not specifically teach a method for treating a mammal having mesothelioma comprising high junction burden but is determined to be absent of an elevated level of polypeptides expressed by at least 6 APP, and administering a cancer treatment that is not an immune checkpoint inhibitor and is surgery or radiation therapy.
However, these deficiencies are made up in the teachings of Shah et al.
Shah et al. teaches a trial designed to study a treatment for early-stage MPM using nivolumab with chemotherapy in pleural mesothelioma after surgery (Abstract and Figure 1). They teach that because of the invasive nature of MPM, surgery is highly recommended for early-stage MPM patients, however complete eradication of the disease by surgery only is unattainable, and thus treatment in the context of multimodal therapy concept is highly recommended (Pg 143 column left spanning paragraph lines 2-6 and Pg 145 column left second full paragraph lines 1-3).
One of ordinary skill in the art would have been motivated, with a reasonable expectation of success, to perform a combined method of treating a mammal having mesothelioma comprising a high level of chromosomal rearrangements as taught by Mansfield et al. and determining that the mesothelioma sample contains the absence of an elevated level of several polypeptides involved in antigen processing and presentation using the techniques as taught by Lee et al., and performing surgery to remove the main tumor volume followed by nivolumab with chemotherapy after surgery as taught by Shah et al. because Shah et al. teaches that the invasive nature of MPM warrants surgery as a highly recommended option for early-stage MPM patients, and that complete eradication of the disease requires inclusion of multimodal therapy approaches such as checkpoint inhibitors and chemotherapy, and because Mansfield et al. teaches that the presence of junction-related or chromosomal rearrangement-related neoantigens in MPM provide favorable responses to immune checkpoint inhibitors (Pg 286 column left paragraph spanning lines 16-26), and further Lee et al. teaches that platinum-based agents and pemetrexed are standard chemotherapy treatments for MPM in accordance with current National Comprehensive Cancer Network guidelines (Pg 7 lines 4-5). This is an example of (A) Combining prior art elements according to known methods to yield predictable results; and (G) Some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention. See MPEP 2143. Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art, absent unexpected results.
Conclusion
No claims are allowed.
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/YIE-CHIA LEE (TONYA)/Examiner, Art Unit 1642
/SEAN E AEDER/Primary Examiner, Art Unit 1642
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