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 preliminary amendments received 06NOV2023 are acknowledged.
Claims 13, 15-32, and 34 have been canceled.
Claims 1, 3-4, 6-7, 9-11, 14, 33, and 35 have been amended.
Claims 36-41 are new.
Claims 1-12, 14, 33, and 35-41 are pending in the instant application (i.e., Claim(s) 1 is/are independent).
Priority
The present application is a continuation application of U.S. Patent Application No. 16/347763, filed 06MAY2019, which is a 371 National Stage of PCT International Application No PCT/EP2017/078 176, filed 03NOV2017, on November 3, 2017, which claims foreign priority under 35 U.S.C. 119 (a)-(d). The certified copy of United Kingdom Application No. 1618743.7, filed 07NOV2016 has been received and is acknowledged.
Information Disclosure Statement
The information disclosure statement(s) (IDS) submitted on 06NOV2023 is/are acknowledged and the references cited therein have been considered.
Specification
The disclosure is objected to because of the following informalities:
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code (p 26 and 30). Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
Appropriate correction is required.
Claim Objections
Claims 6-10, 12, and 41 are objected to because of the following informalities:
Claims 6 and 9 contain acronyms. 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 7-8 and 10 are also objected to since they depend from claims 6 and 9, respectively, but do not remedy this deficiency.
Claim 7 contains a typographical error: “MiK67” should be corrected to “MKi67” in line 3 of the claim.
Claim 8 contains a typographical error: “…the one more tumour…” should be corrected to “…the one or more tumour….”
Claim 8 appears to comprise Markush language and as such should be corrected from “…are selected from….” to “are selected from the group consisting of….” Claims 10, 12, and 41 have the same issue.
Appropriate correction is required.
Claim Rejections - 35 USC § 101
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.
Claims 14 and 36-37 are rejected under 35 U.S.C. 101 because the claimed inventions are not directed to patent eligible subject matter. After consideration of relevant factors with respect to claim(s) 14 and 36-37 as a whole, the claims are directed to mental processes without significantly more. The rationale for this determination is explained below:
Because abstract ideas, laws of nature, and natural phenomenon "are the basic tools of scientific and technological work", the Supreme Court has expressed concern that monopolizing these tools by granting patent rights may impede innovation rather than promote it. See Alice Corp., 573 U.S. at 216, 110 USPQ2d at 1980; Mayo Collaborative Servs. v. Prometheus Labs., Inc., 566 U.S. 66, 71, 101 USPQ2d 1961, 1965 (2012). However, the Court has also emphasized that an invention is not considered to be ineligible for patenting simply because it involves a judicial exception. Alice Corp., 573 U.S. at 217, 110 USPQ2d at 1980-81 (citing Diamond v. Diehr, 450 U.S. 175, 187, 209 USPQ 1, 8 (1981)). Accordingly, the Court has said that integration of an abstract idea, law of nature or natural phenomenon into a practical application may be eligible for patent protection. See, e.g., Alice, 573 U.S. at 217, 110 USPQ2d at 1981 (explaining that "in applying the §101 exception, we must distinguish between patents that claim the ‘buildin[g] block[s]’ of human ingenuity and those that integrate the building blocks into something more" (quoting Mayo, 566 U.S. at 89, 110 USPQ2d at 1971) and stating that Mayo "set forth a framework for distinguishing patents that claim laws of nature, natural phenomena, and abstract ideas from those that claim patent-eligible applications of those concepts"); Mayo, 566 U.S. at 80, 84, 101 USPQ2d at 1969, 1971 (noting that the Court in Diamond v. Diehr found "the overall process patent eligible because of the way the additional steps of the process integrated the equation into the process as a whole." See MPEP §2016.
STEP 1: Is the claim to a process, machine, manufacture, or composition of matter?
Claims 14 and 36-37 are drawn to a process.
[Step 1: Claims 14 and 36-37: yes]
STEP 2A (1st prong): Do the claims recite a judicially-recognized exception (JE), e.g., a law of nature, a natural phenomenon or product, or an abstract idea?
The abstract idea exception has deep roots in the Supreme Court’s jurisprudence. See Bilski v. Kappos, 561 U.S. 593, 601-602, 95 USPQ2d 1001, 1006 (2010) (citing Le Roy v. Tatham, 55 U.S. (14 How.) 156, 174–175 (1853)). Despite this long history, the courts have declined to define abstract ideas. However, it is clear from the body of judicial precedent that software and business methods are not excluded categories of subject matter. The enumerated groupings are firmly rooted in Supreme Court precedent as well as Federal Circuit decisions interpreting that precedent, as is explained in MPEP § 2106.04(a)(2).
The enumerated groupings of abstract ideas are defined as:
1) Mathematical concepts – mathematical relationships, mathematical formulas or equations, mathematical calculations (see MPEP § 2106.04(a)(2), subsection I);
2) Certain methods of organizing human activity – fundamental economic principles or practices (including hedging, insurance, mitigating risk); commercial or legal interactions (including agreements in the form of contracts; legal obligations; advertising, marketing or sales activities or behaviors; business relations); managing personal behavior or relationships or interactions between people (including social activities, teaching, and following rules or instructions) (see MPEP § 2106.04(a)(2), subsection II); and
3) Mental processes – concepts performed in the human mind (including an observation, evaluation, judgment, opinion) (see MPEP § 2106.04(a)(2), subsection III).
Mental process recitation in claim14: “…determining a suitable treatment based on the properties of the tumour from which the 3D cell-free scaffold was obtained” under BRI this step is considered an abstract idea in the “mental processes” group. For example, evaluating information and providing an opinion regarding a suitable treatment based on the information evaluation is an act that can be practically performed in the human mind.
Mental process recitation in claims 36-37: “…comparing the one or more properties of the tumour from which the second 3D cell-free scaffold was obtained” determined in prior steps under BRI this step is considered an abstract idea in the “mental processes” group. For example, a comparison of collected information (i.e., one or more tumour properties after treatment) to a threshold (i.e., one or more tumour properties prior to treatment) is an act of evaluating information that can be practically performed in the human mind.
[Step 2A (1st prong): Claims 14 and 36-37: yes]
STEP 2A (2nd prong): Do the claims recite additional elements that integrate the judicial exception into a practical application?
The Supreme Court has long distinguished between principles themselves (which are not patent eligible) and the integration of those principles into practical applications (which are patent eligible). See, e.g., Mayo Collaborative Servs. v. Prometheus Labs., Inc., 566 U.S. 66, 80, 84, 101 USPQ2d 1961, 1968-69, 1970 (2012) (noting that the Court in Diamond v. Diehr found ‘‘the overall process patent eligible because of the way the additional steps of the process integrated the equation into the process as a whole,’’ but the Court in Gottschalk v. Benson ‘‘held that simply implementing a mathematical principle on a physical machine, namely a computer, was not a patentable application of that principle’’). The Supreme Court and Federal Circuit have identified a number of considerations as relevant to the evaluation of whether the claimed additional elements demonstrate that a claim is directed to patent-eligible subject matter.
Limitations the courts have found indicative that an additional element (or combination of elements) may have integrated the exception into a practical application include:
• An improvement in the functioning of a computer, or an improvement to other technology or technical field, as discussed in MPEP §§ 2106.04(d)(1) and 2106.05(a);
• Applying or using a judicial exception to effect a particular treatment or prophylaxis for a disease or medical condition, as discussed in MPEP § 2106.04(d)(2);
• Implementing a judicial exception with, or using a judicial exception in conjunction with, a particular machine or manufacture that is integral to the claim, as discussed in MPEP § 2106.05(b);
• Effecting a transformation or reduction of a particular article to a different state or thing, as discussed in MPEP § 2106.05(c); and
• Applying or using the judicial exception in some other meaningful way beyond generally linking the use of the judicial exception to a particular technological environment, such that the claim as a whole is more than a drafting effort designed to monopolize the exception, as discussed in MPEP § 2106.05(e).
The courts have also identified limitations that did not integrate a judicial exception into a practical application:
• Merely reciting the words "apply it" (or an equivalent) with the judicial exception, or merely including instructions to implement an abstract idea on a computer, or merely using a computer as a tool to perform an abstract idea, as discussed in MPEP § 2106.05(f);
• Adding insignificant extra-solution activity to the judicial exception, as discussed in MPEP § 2106.05(g); and
• Generally linking the use of a judicial exception to a particular technological environment or field of use, as discussed in MPEP § 2106.05(h).
In this instance, “a method for determining a suitable treatment for a patient with a tumour…“ or “a method for determining or monitoring efficacy of a treatment for a patient with a tumour…” or “a method for determining likely efficacy of a treatment for a patient with a tumor…” comprising steps directed to mental processes (i.e., correlation of results with potential treatment or comparison of sample results prior to and following treatment) does not require the artisan to integrate the JEs into a practical application (i.e., fails to further limit the invention in a manner to use in a practical application). For example, the methods of claims 14 and 36-37 fail to integrate the comparison into a practical application such as actively adjusting the treatment step, personalizing the treatment step, or applying the treatment based on the result of the correlation or comparisons. Furthermore, the methods of claims 14 and 36-37, are an evaluation of collected data which is correlated to potential treatments providing an opinion about the suitability of a treatment or an evaluation of collected data from before and after treatment, respectively, which are considered routine and conventional in the medical field.
[Step 2A (2nd prong): Claims 14 and 36-37: no]
STEP 2B: Do the claims recite a non-conventional arrangement of additional elements that amounts to significantly more than the judicial exception (i.e., Do the additional elements contribute an “inventive concept”?
The second part of the Alice/Mayo test is often referred to as a search for an inventive concept. Alice Corp. Pty. Ltd. v. CLS Bank Int'l, 573 U.S. 208, 217, 110 USPQ2d 1976, 1981 (2014) (citing Mayo Collaborative Servs. v. Prometheus Labs., Inc., 566 U.S. 66, 71-72, 101 USPQ2d 1961, 1966 (2012)).
All elements of claims 14 and 36-37 are part of one or more identified JEs (as described above) and do not contain additional elements that are sufficient to amount to significantly more than the judicial exception because each element/step when considered independently and in combination are considered well understood, routine, and conventional. Furthermore, it is understood in the medical field that determining a suitable treatment for a patient is conventionally done by a physician assessing the patient and any blood test, biopsy, and/or imaging results to determine a diagnosis and then reviewing the clinical efficacy of treatments for said diagnosis to determine a suitable treatment; and similarly determining or monitoring efficacy of treatment may be done with conventional metrics such as reduction in tumour volume as measured by imaging, determining biomarker levels in blood, etc. by comparing the tumour or blood results prior to and following treatment, consisting of the elements/steps of claims 14 and 36-37, respectively. Additionally, in the instance of vimentin, the overexpression of vimentin has been linked to the aggressive phenotype in triple negative breast cancer, provides an independent prognostic factor for TNBC, and has been proposed as an attractive and promising therapeutic target for TNBC patients (Yamashita, et al., J Canc Res Clin Oncol, 2013, 139, 739-746, see abstract and conclusion) and furthermore, vimentin has been used as a marker for detecting mesenchymal circulating tumor cells (i.e., CTCs that have undergone epithelial-mesenchymal transition (EMT)) in breast cancer patients thereby improving the clinical assessment of therapeutic response (Satelli, et al., Clin Chem, 2015, 61, 259-266, see introduction).
[Step 2B: Claims 14 and 36-37: no]
Summary and conclusion regarding claims 14 and 36-37:
In conclusion, the above 101 JE analysis of claims 14 and 36-37, viewed as a whole and considering all elements individually and in combination, no claim recites limitations that transform the claim, finally interpreted as directed to the above-identified JE(s), into patent eligible subject matter.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 8 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 8 recites the limitation "A method according to claim 7, wherein at least one of the one or more markers is selected from…and wherein the one or more tumour progressive properties comprise tumour recurrence." In this instance, claim 7 drawn to the one or more markers is dependent on claim 6, drawn to at least one or more markers is dependent on claim 5 drawn to the one or markers of tumour progression are selected from markers of proliferation, markers of differentiation, markers of cancer stem cells, and markers of EMT, which is dependent on claim 4 drawn to one or more genes are one or more markers of tumour progression, which is dependent on claim 1, drawn to a method for determining one or more properties of a tumour in a patient. Therefore there is insufficient antecedent basis for this limitation of “tumour recurrence” in the claim. Examiner notes, that if claim 8 were dependent on claim 3 or if claim 8 were amended from “…wherein the one or more tumour progressive properties comprise tumour recurrence.” to “…wherein the one or more properties of the tumour from which the 3D cell-free scaffold was obtained is tumour recurrence.” or something of similar nature would obviate the rejection.
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 1-12, 14, 33, and 35-41 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 for determining one or more properties of a tumour in a patient, the method comprising:
i) seeding a 3-dimensional decellularised scaffold obtained from the tumour in the patient with a cancer cell line, wherein the cancer cell line is the same tissue type or cancer type as the tumour from which the 3-dimensional decellularised scaffold has been obtained,
ii) culturing the cancer cell line in the scaffold;
iii) assaying the cultured cancer cell line for the presence of target molecules indicative of the expression of one or more genes in the cells; and
iv) determining one or more properties of the tumour from which the 3-dimensional decellularised scaffold was obtained based on the presence of target molecules indicative of the expression of one or more genes in the cells in the assay;
wherein the one or more genes are one or more markers of tumour progression; and
wherein the one or more markers of tumour progression consist of SOX2, CD44; SNAIL1; SNAIL2; and VIM.” (Claims 1 and 6 as well as 4, and 7-8);
-AND-
“A method for determining one or more properties of a tumour in a patient, the method comprising:
seeding a 3-dimensional cell-free scaffold obtained from the tumour in the patient with cancer cells, wherein the cancer cells are not taken from the tumour in the patient;
culturing the cancer cells in the scaffold;
assaying the cultured cancer cells for the presence of target molecules indicative of the expression of one or more genes in the cells; and
determining one or more properties of the tumour from which the 3-dimensional cell-free scaffold was obtained based on the presence of target molecules indicative of the expression of one or more genes in the cells in the assay; and
wherein the one or more genes are selected from the group consisting of: ACTN1; AIFM1; ALDH2; ALDOA; ANXA1; AP1B1; AP2B1; ATM; ATXN1; BAG2; BAG3; BHLHE40; BIRC5; BTBD2; BYSL; C3; CAMK2B; CAMK4; CARD11; CASP3; CAV1; CEACAM1; CHD3; COL17A1; CRCT1; DAPK1; DMD; DPYSL2; DYSF; E2F1; EGFR; EIF2AK3; EP300; EPOR; ERBB3; ESR1; FANCC; FEN1; FHIT; FKBP5; FN1; FOS; FRMD6; GADD45A; GADD45G; GOLM1; GSN; GSTP1; HCK; HDAC5; HSPB1; HSPD1; IGF1R; IL4R; ITGA6; ITGB4; JAK1; JUN; KAT2B; KIF15; KRT18; KRT8; LYST; LRP1; LRPS; MAP2; MAP3K14; MAP3K5; MAPK3; MAPKAPK3; MST1R; NDRG1; NME1-NME2; NOS3; NPAS2; NPHP1; NQO1; NR3C; PIK3CG; PAEP; PAK1; PARK2; PARP1; PDE4D; PFN2; PIM1; PTN; PKD1; PLA2G4A; PLD1; PPARGC1A; PPL; PPM1A; PPP1R15A; PPP2R1B; PRKCA; PRNP; PSG9; PSME3; RABAC1; RAC2; RASA1; RBL1; RGS2; RPS6KA3; RUNX1T1; SH2B3; SH3GL3; SLC9A3R1; SMAD4; SNX9; SORBS2; SOX9;SP1; SPG7; SREBF1; STUB1; SUMO4; SVIL; TGFB1 11; TH; TNFAIP3; TNFRSF14; TNIK; TP73; TPD52L1; TRIO; TUBA1A; VIM; WEE1; XPO5;YAP1; and ZNF259.” (claims 1 and 9 and as enabled in published patent US 11840732);
-AND-
“A method of treating a patient with a tumour, the method comprising:
i) determining one or more properties of the tumour from which the 3-dimensional decellularised scaffold was obtained according to the method of claim 1;
ii) determining a suitable treatment based on the properties of the tumour from which the 3D decellularised scaffold was obtained;
iii) selecting the treatment; and
iv) administering the treatment to the patient” (Amended claim 1/6 or 1/9 and Claims 14 and 33 and claim 35);
-AND-
“A method of treating a patient with a tumour, the method comprising:
i) determining one or more properties of the tumour from which the 3-dimensional decellularised scaffold was obtained according to the method of claim 1, wherein the 3-dimensional decellularised scaffold has been obtained from the patient before the treatment has been provided to the patient;
ii) determining one or more properties of the tumour from which the 3-dimensional decellularised scaffold was obtained according to the method of claim 1, wherein the 3-dimensional decellularised scaffold has been obtained from the patient after the treatment has been provided to the patient;
iii) determining the efficacy of the treatment by comparing the one or more properties from which the 3-dimensional decellularised scaffold was obtained determined in i) and ii); and
iv) administering the effective treatment to the patient.” (Amended claim 1/6 or 1/9 and Claims 36 and 38);
-AND-
“A method of treating a patient with a tumour, the method comprising:
i) determining one or more properties of the tumour from which the 3-dimensional decellularised scaffold was obtained according to the method of claim 1, wherein the decellularised scaffold has been obtained from the patient before the treatment has been provided to the patient and a treatment is not administered to the cultured cancer cell line;
ii) determining one or more properties of the tumour from which the 3-dimensional decellularised scaffold was obtained according to the method of claim 1, wherein the decellularised scaffold has been obtained from the patient before the treatment has been provided to the patient and a treatment is administered to the cultured cancer cell line;
iii) determining the efficacy of the treatment by comparing the one or more properties from which the 3-dimensional decellularised scaffold was obtained determined in i) and ii); and
iv) administering the effective treatment to the patient.” (Amended claim 1/6 or 1/9 and Claims 37 and 39); 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.
Scope of the claim:
In the instance of claim 1 drawn to a method for determining essentially any property of essentially any tumour in a patient the method comprising: seeding a cell-free scaffold obtained from the essentially any tumor in the patient with essentially any cancer cells with exception of cancer cells from the source tumour, is not fully enabled. In addition to the specific rejections of claims 6-8, 14, 33, and 35-39, claims 2-4, 5, 9-12, and 40-41 are also rejected since they are dependent on claim 1, but do not fully remedy this deficiency. The reasons that claims 1, 6-8, 14, 33, and 35-39, are not fully enabled is because of:
i) The breadth of determining essentially any property of essentially any tumour using the decellularised scaffold of the essentially any tumour/any organ using essentially any reporter cancer cell line (except from the source) recited in claims 1, 14, 33, 35-39. (i.e., claim 2 limits the tumour type to breast cancer, but does not provide limitation to the properties of the tumour nor reporter cell line; claims 3-10 limits the properties of the tumour but does not provide limitation to the tumour type, cancer of a certain organ, nor reporter cancer cell line; claims 11-12 limits the reporter cancer cell to breast cancer cells or cell lines of MCF7, MDAMB231, and T47D but does not provide limitation to the tumour type, cancer of a certain organ, nor tumour properties; claim 40 limits the patient to human but does not provide limitations to tumour property, tumour or organ with cancer, nor reporter cancer cell line; and claim 41 dependent on claim 2, limits the tumour type and partially provides limitations around tumour properties but does not list specific assayed genes/markers and does not provide limitations around the reporter cancer cell lines).
ii) The teaching of the prior art that not all properties of tumours are expressed in all types of cell lines or cancer cell tissues; for example, according to the Human Protein Atlas, NANOG RNA expression was negligible (i.e., 0-0.1 normalized transcript per million (nTPM)) in MCF7, MDA-MB-231, and T-47D cell lines and was 0.2-0.3 nTPM across over 1000 invasive breast carcinoma samples. In comparison, RNA expression was 23.7 nTPM in the SuSa cell line (i.e., human testicular germ cell line in HPA), 157.6 nTPM in the NTERA2 cell line (i.e., uncategorized cell line in HPA, but was isolated from the testis of a male patient with carcinoma, malignant pluripotent embryonal according to ATCC) and 239 nTPM across 130 testicular germ cell samples. Furthermore, Lu, et al. teach that overexpression of NANOG in the mammary gland is not sufficient to induce a mammary tumor; however upon co-expression with Wnt-1 in the mouse mammary gland, it promotes mammary tumorigenesis and metastasis (Lu, et al., Oncogene, 2013, 20, 2655-2664, see abstract). Therefore, the prior art supports that NANOG alone may not be an effective factor for determining one or more properties of a tumour (i.e., invasiveness, migration, malignancy grade, malignancy potential, recurrence, resistant to treatment, and proliferation) from which the 3D decellularised scaffold was obtained as recited in instant claims 1-6, 11-12, 14, 33, 35-41. Furthermore, it is unclear without significant experimentation for one of ordinary skill in the art that all other markers in claims 6 or 9 individually would provide enough information alone to determine specific properties of the tumour, much less a method of treatment.
iv) The specification teaching that suitable cells may be determined according to the tumour from which the scaffold has been obtained, for example the same tissue type or cancer type (i.e., if the decellularised scaffold is from a tumour of the breast, then the cancer cells may be breast cancer cells, such as cancer cell lines MCF7, MDA-MB-231, or T47D cells) (p 11-12 of the originally filed specification). Furthermore, the working examples support the scaffold and the seeded and cultured cancer cells to be from the same tissue (i.e., breast cancer tumour from which the decellularised 3D scaffold was obtained used with breast cancer cell lines), wherein the cell lines (Fig 8) and that in combination SOX2, CD44; SNAIL1; SNAIL2; and VIM showed increases over time of culturing (i.e., SOX2, SNAIL1), similar results in the scaffold as well as in the xenograft (i.e., SOX2, CD44, SNAIL1, SNAIL2, and VIM), and cluster differences over 47 different scaffolds (i.e., SNAIL2 and VIM, and CD44, and SOX2) (Fig 12; Fig 13; and Fig 21-22, respectively). Furthermore, the specification teaches seeding and culturing MCF7 cells in 46 decellularised ductal breast cancer scaffolds and that CCNB2, EPCAM, and POU5[F]1 did not pass quality demands and therefore were not included in the analysis of the 46 scaffolds (p 35, line 22-26). Additionally, 10 of the 46 scaffolds were linked to recurrences (Fig 22) and VIM and SNAIL2 (i.e., also known as SLUG) overexpression in MCF7 reporter cell lines in the 10 scaffolds linked to recurrences correlated to lower overall survival following surgery (Fig 23-24). Although, VIM and SNAIL2 showed a correlation to recurrence, it is unclear whether VIM or SNAIL2 are correlated to markers of tumour progression in all breast cancer reporter cell lines or different decellularised scaffolds and reporter cancer cell line combinations; and it is unclear whether a single or a panel of tumour progression markers are necessary to determine/select/adjust a cancer patients treatment as recited in claims 1-8, 11-12, 14, 33, 35-41).
v) Therefore, the implementation of the invention in view of the breadth of variables (i.e., any properties of any tumour, any reporter cancer cell line, etc.), low level of predictability in the art, specific working examples which support a specific set of properties (i.e., markers of tumour progression) in patients having a breast cancer tumour using breast cancer reporter cell lines), would require undue experimentation for one of ordinary skill in the art to use the methods for determining one or more properties of a tumour and/or the methods of treating a patient with a tumour.
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 1-12, 14, 33, 35, and 40-41 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-13 of U.S. Patent No. 11,840,732 (Landberg, et al.,), herein referred to as “’732.” Although the claims at issue are not identical, they are not patentably distinct from each other because the method of determining one or more properties of a tumour in a patient of the ‘732 patent anticipates the method of determining one or more properties of a tumour in a patient of the instant application as shown in the Table below.
Issued claims of the ‘732 patent:
Instant Application patent claims, underline corresponds to direct mapping to claim 1 of the ‘732 patent and italics corresponds to the additional claim limitations.
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465
292
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Greyscale
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478
289
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Greyscale
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302
288
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Greyscale
1. A method for determining one or more properties of a tumour in a patient, the method comprising:
seeding a 3-dimensional cell-free scaffold obtained from the tumour in the patient with cancer cells, wherein the cancer cells are not taken from the tumour in the patient;
culturing the cancer cells in the scaffold;
assaying the cultured cancer cells for the presence of target molecules indicative of the expression of one or more genes in the cells; and
determining one or more properties of the tumour from which the 3-dimensional cell-free scaffold was obtained based on the presence of target molecules indicative of the expression of one or more genes in the cells in the assay.
2. A method according to claim 1 wherein the tumour is a breast cancer tumour.
3. A method according to claim 1 wherein the one or more tumour properties are selected from invasiveness, migration, tumour malignancy grade, tumour malignancy potential, tumour recurrence, resistance to treatment and tumour proliferation.
4. A method according to claim 1 wherein the one or more genes are one or more markers of tumour progression.
5. A method according to claim 4 wherein the one or more markers of tumour progression are selected from markers of proliferation, markers of differentiation, markers of cancer stem cells, and markers of epithelial-mesenchymal transition (EMT).
6. A method according to claim 5 wherein at least one of the one or more markers is selected from a group consisting of CCNB2; CCNA2; CDKNIA; CDKN2A; MKi67; CDK4; CDK6; EPCAM; PGR; ESR1; CD24; CDH1; ERBB2; POU5F1; NANOG; SOX2; FOSL1; TGFB1; CD44; ALDH1A1; ALDH1A3; ABCG2; SNAIL1; TWIST1; SNAIL2; VIM; and CDH2.
7. A method according to claim 6 wherein at least one of the one or more markers is selected from a group consisting of: CD44v2, SOX2, SNAIL2(SLUG), VIM, ESR 1, ERBB2(HER2), MiK67 and CCNA2.
8. A method according to claim 7 wherein at least one of the one or more markers is selected from SNAIL2(SLUG) and VIM, and wherein the one more tumour progressive properties comprise tumour recurrence.
9. A method according to claim 1, wherein the one or more genes are selected from the group consisting of: ACTN1; AIFM1; ALDH2; ALDOA; ANXA1; AP1B1; AP2B1; ATM; ATXN1; BAG2; BAG3; BHLHE40; BIRC5; BTBD2; BYSL; C3; CAMK2B; CAMK4; CARD11; CASP3; CAV1; CEACAM1; CHD3; COL17A1; CRCT1; DAPK1; DMD; DPYSL2; DYSF; E2F1; EGFR; EIF2AK3; EP300; EPOR; ERBB3; ESR1; FANCC; FEN1; FHIT; FKBP5; FN1; FOS; FRMD6; GADD45A; GADD45G; GOLM1; GSN; GSTP1; HCK; HDAC5; HSPB1; HSPD1; IGF1R; IL4R; ITGA6; ITGB4; JAK1; JUN; KAT2B; KIF15; KRT18; KRT8; LYST; LRP1; LRPS; MAP2; MAP3K14; MAP3K5; MAPK3; MAPKAPK3; MST1R; NDRG1; NME1-NME2; NOS3; NPAS2; NPHP1; NQO1; NR3C; PIK3CG; PAEP; PAK1; PARK2; PARP1; PDE4D; PFN2; PIM1; PTN; PKD1; PLA2G4A; PLD1; PPARGC1A; PPL; PPM1A; PPP1R15A; PPP2R1B; PRKCA; PRNP; PSG9; PSME3; RABAC1; RAC2; RASA1; RBL1; RGS2; RPS6KA3; RUNX1T1; SH2B3; SH3GL3; SLC9A3R1; SMAD4; SNX9; SORBS2; SOX9;SP1; SPG7; SREBF1; STUB1; SUMO4; SVIL; TGFB1 11; TH; TNFAIP3; TNFRSF14; TNIK; TP73; TPD52L1; TRIO; TUBA1A; VIM; WEE1; XPO5;YAP1; and ZNF259.
10. A method according to claim 9, wherein the one or more genes are selected from ATXN1; EGFR; FN1; LRP1; NDRG1; PRKCA; SMAD4; SUMO4; SVIL; VIM; C3; EP300; ESR1; KRTI8; ACTN1 and CASP3.
11. A method according to claim 1 wherein the cancer cells are breast cancer cells.
12. A method according to claim 11 wherein the cancer cells are selected from MCF7, MDA231, and T47D.
14. A method for determining a suitable treatment for a patient with a tumour, the method comprising: determining one or more properties of the tumour from which the 3-dimensional cell-free scaffold was obtained by a method according to claim 1; and determining a suitable treatment based on the properties of the tumour from which the 3-dimensional cell-free scaffold was obtained.
33. A method of treating a patient with a tumour, the method comprising: determining the suitability of a treatment in the patient by a method according to claim 14; and applying the treatment to the patient.
35. A method of treating patient with a tumour, the method comprising: determining one or more properties of the tumour from which the 3-dimensional cell-free scaffold was obtained in the patient by a method according to claim 1; selecting a suitable treatment based on the one or more properties of the tumour from which the 3-dimensional cell-free scaffold was obtained; and providing the treatment to the patient.
40. A method according to claim 1, wherein the patient is a human patient.
41. A method according to claim 2 wherein the one or more properties of the tumour from which the 3-dimensional cell-free scaffold was obtained are selected from invasiveness, migration, tumour malignancy grade, tumour malignancy potential, tumour recurrence, resistance to treatment and tumour proliferation.
In this instance, claim 1 of the ‘732 patent anticipates claim 1 of the instant application because the ‘732 patent recites species of the instant application genus (i.e., the reference species anticipates the broader scope of the instant application). Therefore there is no clear difference in the scope between the methods of the instant application and the ’732 patent.
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1, 3-12, 37, and 41 are rejected under 35 U.S.C. 103 as being unpatentable over Lu, et al., (PLOS One, 2014, 9, 1-13), herein referred to as “Lu” and in view of Dunne, et al., (Biomaterials, 2014, 35, 4940-4949), herein referred to as “Dunne.”
Lu teaches the decellularization of sliced sheets of A549 (i.e., human pulmonary adenocarcinoma) xenograft tumors 30 days post implantation and MCF7 (i.e., human breast cancer) cells were grown in the scaffolds (see entire document, specifically see abstract section). Furthermore, Lu teaches that decellularized tumor extracellular matrices are promising 3D scaffolds with ideal spatial arrangement, biomechanical properties and biocompatibility for improved modeling of 3D tumor microenvironments (abstract section) and that further studies are necessary to explore the malignant phenotype in 3D culture, hypoxia with an extended culture time, and cellular responses to chemotherapeutic agents (last sentence of last paragraph).
However, they do not teach: assaying the cultured cells for the presence of target molecules indicative of the expression of one or more genes in the cells and determining one or more properties of the tumour from the assayed cells; or methods of determining likely efficacy of a treatment for a patient with a tumour.
Nevertheless, Dunne teaches the use of decellularized human adipose tissue (i.e., used in breast reconstruction following surgical removal of breast tumour) to recapitulate the microenvironment of mammary adipose tissues surrounding breast cancer cells or in this instance for growing breast cancer cell lines and determining cell proliferation, migration, expression of adhesion molecules (i.e., vimentin) and drug response (i.e., likely efficacy of a treatment) of the human decellularized adipose scaffold (i.e., hDAM scaffolds) (see entire document, specifically see introduction section and Fig 1). The hDAM scaffold was seeded with either MCF7, BT474, or SKBR3 cell lines (see section 3.5). In the hDAM scaffold comprising MCF7 or BT474, vimentin expression was higher in both the hDAM scaffold and xenograft models than the 2D or Matrigel models (Fig 4B). Furthermore, Dunne teaches that expression of EGFR only slightly differs between 2D-cultured cells, hDAM scaffolds, and xenografts of BT474 and SKBR3, whereas pEGFR and pAKT were highly expressed in both hDAM and xenografts of BT474 and SKBR3, and following treatment with lapatinib (i.e., an EGFR inhibitor), the expression of pEGFR and pAKT were effectively reduced (i.e., a method for determining the likely efficacy of a treatment) (see section 3.8 and Fig 7A-7B). Dunne further teaches that 3D decellularized scaffolds would be useful in investigating the changes in signaling pathways in said scaffolds providing additional insights regarding the impact of the scaffold on cancer signaling and that the 3D decellularized scaffolds provide a proof of concept of biomimetic, tissue-specific scaffolds for cell-based drug screening (see sections 4 and 5).
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 A549 decellularized scaffold seeded with MCF7 cells disclosed by Lu by evaluating the adhesion (i.e., vimentin) or other targets of interest (i.e., EGFR) of the cancer cells disclosed by Dunne because changes in expression of specific genes/markers of tumor progression provides a way of understanding the signaling that occurs in cancer cells based on the scaffold and a method for screening treatments based on protein expression of the cancer cells cultured in the 3D scaffolds (i.e., determining the likely efficacy of a therapeutic). One would have been motivated to do so, given the teachings of Lu that the decellularized tumor extracellular matrices are promising 3D scaffolds with ideal spatial arrangement, biomechanical properties and biocompatibility for improved modeling of 3D tumor microenvironments and that further studies are necessary to determine cellular responses to chemotherapeutic agents for example. There would have been a reasonable expectation of success, given the knowledge that utilizing a decellularized 3D scaffold would provide a mechanism to grow cancer cell lines, which provided similar protein expression as a xenograft which also provided a method to determine the properties and screen drugs for likely efficacy as taught by Dunne.
Thus, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time of filing.
Conclusion
No claims are allowed.
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/MISOOK YU/Supervisory Patent Examiner, Art Unit 1641
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