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 .
DETAILED ACTION
Election/Restriction
Applicant’s election, with traverse, of Group I, claims 1-10, drawn to a method of determining resistance to anticancer agent or radiation of a subject with cancer, in the reply filed on 06/18/2025 is acknowledged. The traversal is on the ground(s) that the subject matter of Groups I and II are sufficiently related. This is found persuasive thus the restriction requirement is withdrawn. Applicant is reminded that the Examiner has been changed during the course of prosecution.
Rejoinder
The restriction requirement between Groups I and II, as set forth in the Office action mailed on 05/21/2025, has been reconsidered in view of the prior art and Applicant’s argument. The restriction requirement between Groups I and II is hereby withdrawn. Claim 11, directed to previously non-elected Group II is no longer withdrawn from consideration.
In view of the above noted withdrawal of the restriction requirement, applicant is advised that if any claim presented in a continuation or divisional application is anticipated by, or includes all the limitations of, a claim that is allowable in the present application, such claim may be subject to provisional statutory and/or nonstatutory double patenting rejections over the claims of the instant application.
Once a restriction requirement is withdrawn, the provisions of 35 U.S.C. 121 are no longer applicable. See In re Ziegler, 443 F.2d 1211, 1215, 170 USPQ 129, 131-32 (CCPA 1971). See also MPEP § 804.01.
Claim Status
Claims 1-11 are pending and are considered on the merits.
Priority
This application is a 371 of PCT/KR2020/008285 (filed on 06/25/2020). The priority claim of the instant application has been granted and the earliest benefit date is 06/25/2020 from PCT/KR2020/008285.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 01/21/2022, 03/13/2025, 04/14/2025, 05/02/2025, 05/09/2025, 05/19/2025 and 10/24/2025 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner. The corresponding signed and initialed PTO forms 1449 have been mailed with this action.
Claim Objections
Claims 1-3 and 11 are objected to because of the following informalities:
Claim 1 recites a symbol “:” in the phrase “a 3D cell culture plate:” in line 4. It is recommended to change it to “;” (i.e., “a 3D cell culture plate;”) to be consistent with other steps.
Furthermore, claim 1 recites the phrase “as a cancer organoid having resistance to an anticancer agent” in line 8. Since the previous step of treating has already recited an anticancer agent, it is recommended to change the phrase to “as a cancer organoid having resistance to the anticancer agent”.
Claim 2 recites the phrases “as a cancer organoid having resistance to an anticancer agent” in lines 2-3 and lines 3-4. It is recommended to change the phrases to “as the cancer organoid having resistance to the anticancer agent”. Claim 2 recites the phrase “before treatment with an anticancer agent” in the last 2 lines. It is recommended to change to “before treatment with the anticancer agent”.
Claim 3 recites the phrases “as a cancer organoid having resistance to an anticancer agent” in lines 2-3 and lines 3-4. It is recommended to change the phrases to “as the cancer organoid having resistance to the anticancer agent”. Claim 3 recites the phrase “before treatment with an anticancer agent” in the last 2 lines. It is recommended to change to “before treatment with the anticancer agent”.
Claim 11 recites a symbol “:” in the phrase “a 3D cell culture plate:” in line 4. It is recommended to change it to “;” (i.e., “a 3D cell culture plate;”) to be consistent with other steps.
Furthermore, claim 11 recites the phrase “as a cancer organoid having resistance to an anticancer agent” in line 8. Since the previous step of treating has already recited an anticancer agent, it is recommended to change the phrase to “as a cancer organoid having resistance to the anticancer agent”.
In claim 11, line 11, there is no punctuation mark at the end of the sentence. It is recommended to add a “;” after the term “radiation”.
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 1-11 are rejected under 35 U.S.C. 101 because the claimed invention is not directed to patent eligible subject matter. Based upon an analysis with respect to the claim as a whole, the claims listed above do not recite something significantly different than a judicial exception. Judicial exceptions include abstract ideas, laws of nature/natural principles, natural phenomena, and natural products. As described in MPEP § 2106, in addition to the terms laws of nature, physical phenomena, and abstract ideas, judicial exceptions have been described using various other terms, including natural phenomena, products of nature, natural products, naturally occurring things, scientific principles, systems that depend on human intelligence alone, disembodied concepts, mental processes and disembodied mathematical algorithms and formulas, for example. The exceptions reflect the judicial view that these fundamental tools of scientific and technological work are not patentable.
The claimed invention is not patent eligible since each claim, as a whole, does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the claims relate to a decision tree required by the claimed invention before selecting a cancer organoid having resistance to an anticancer agent and/or radiation that involve steps that may be performed mentally and that do not add significantly more to the claimed invention. Specifically, these steps that may be performed mentally relate to selecting a cancer organoid having resistance to an anticancer agent and/or radiation (e.g., in claim 1) and comparing a cancer organoid treated with a candidate material with a control and determining the candidate material as a drug for alleviating the drug resistance of cancer cells (e.g., in claim 11).
This conclusion was reached by following the procedure set forth in an official guidance memorandum issued on March 4, 2014 by Andrew Hirshfeld, Deputy Commissioner for Patent Examination Policy, entitled “Guidance For Determining Subject Matter Eligibility Of Claims Reciting Or Involving Laws of Nature, Natural Phenomena, & Natural Products” (hereinafter “guidance”; available at http://www.uspto.gov/patents/law/exam/myriad-mayo_guidance.pdf).
To expound upon the above, the decision in Alice Corp. v. CLS Bank made clear that it applies the framework set forth in Mayo Collaborative Services v. Prometheus Laboratories, Inc., 566 U.S. (2012) (Mayo) to analyze all claims directed to laws of nature, natural phenomena and abstract ideas for subject matter eligibility under 35 USC 101 (also see reasoning set forth below regarding natural principals). The instructions in Alice indicate the following:
1) The same analysis should be used for all types of judicial exceptions, whereas prior USPTO guidance applied a different analysis to abstract ideas (Bilski guidance in MPEP at 2106 (II)(B)) than to claims with laws of nature (Mayo guidance in MPEP 2106.01).
2) The same analysis should be used for all categories of claims (e.g., product and process claims) where prior guidance applied a different analysis to process claims (Bilski guidance).
The basic inquiries remain the same, however, as explained in MPEP 2106(I). With regard to that, and analyzing the instant claims herein, the first question to ask is do the claims fall into one of the four categories of invention (i.e., step 1)? The answer here is “yes”. The claims are drawn to a process.
The next question relates to whether the claimed invention is directed to a law of nature, a natural phenomenon, or an abstract idea (i.e. question 2A prong one). The invention as presently claimed is directed to a judicial exception, since the claimed invention requires the act of selecting a cancer organoid having resistance to an anticancer agent and/or radiation (e.g., in claim 1) and comparing a cancer organoid treated with a candidate material with a control and determining the candidate material as a drug for alleviating the drug resistance of cancer cells (e.g., in claim 11). Each of these steps can be performed mentally, and are thus considered abstract ideas. The answer to step 2A prong one is thus “yes”.
Proceeding to step 2A prone two of the analysis becomes important to determine whether the claims recite additional elements that integrate the judicial exception into a practical application. Although the claims recite addition elements (e.g., isolating, culturing and treating cancer organoids) before selecting a cancer organoid having resistance to an anticancer agent and/or radiation in claim 1, or additional elements of treating with a candidate material before comparing and determining the candidate material as a drug for alleviating the drug resistance of cancer cells in claim 11, there are no additional elements recited based on the steps directed to judicial exceptions. Therefore, the claims do not recite additional elements that integrate the judicial exception into a practical application. The answer to step 2A prong two is thus “no”.
Turning to step 2B, the claim as a whole does not amount to significantly more than the abstract ideas since they do not comprise an improvement to an technology or field, or a computer, or effect a transformation of a particular article to a different state or thing or add significantly specific limitations to the abstract ideas other than what is well understood, routine and conventional in the field. It is well established that the mere physical or tangible nature of additional elements, such as the isolating, culturing and treating organoids, does not automatically confer eligibility on a claim directed to an abstract idea (see, e.g., Alice Corp. v. CLS Bank Int’l, 134 S.Ct. 2347, 2358-59 (2014)). The claimed invention is thus drawn to abstract ideas (that cannot confer patent eligibility as discussed above), and additional elements of isolating, culturing and treating cancer organoids with anticancer agents/radiation or a candidate material. Here however, the steps of isolating, culturing and treating cancer organoids with anticancer agents/radiation or a candidate material, cannot be relied upon to confer eligibility. This is because the steps do not add significantly specific limitations to the abstract ideas other than what is well understood, routine and conventional in the field. Furthermore, there are no additional elements recited based on the steps directed to judicial exceptions. Accordingly, the claims encompass methods that do not apply the abstract idea in a meaningful or specific way so as to render the claims practically applied. The answer to question 2B above is thus “no”.
In light of the above considerations and cited guidance, the claims are thus drawn to patent ineligible subject matter and are rejected therefore.
Claim Interpretation and Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(f):
(f) Element in Claim for a Combination. – An element in a claim for a combination may be expressed as a means or step for performing a specified function without the recital of structure, material, or acts in support thereof, and such claim shall be construed to cover the corresponding structure, material, or acts described in the specification and equivalents thereof.
The following is a quotation of pre-AIA 35 U.S.C. 112, sixth paragraph:
An element in a claim for a combination may be expressed as a means or step for performing a specified function without the recital of structure, material, or acts in support thereof, and such claim shall be construed to cover the corresponding structure, material, or acts described in the specification and equivalents thereof.
The claims in this application are given their broadest reasonable interpretation using the plain meaning of the claim language in light of the specification as it would be understood by one of ordinary skill in the art. The broadest reasonable interpretation of a claim element (also commonly referred to as a claim limitation) is limited by the description in the specification when 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is invoked.
As explained in MPEP § 2181, subsection I, claim limitations that meet the following three-prong test will be interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph:
(A) the claim limitation uses the term “means” or “step” or a term used as a substitute for “means” that is a generic placeholder (also called a nonce term or a non-structural term having no specific structural meaning) for performing the claimed function;
(B) the term “means” or “step” or the generic placeholder is modified by functional language, typically, but not always linked by the transition word “for” (e.g., “means for”) or another linking word or phrase, such as “configured to” or “so that”; and
(C) the term “means” or “step” or the generic placeholder is not modified by sufficient structure, material, or acts for performing the claimed function.
Use of the word “means” (or “step”) in a claim with functional language creates a rebuttable presumption that the claim limitation is to be treated in accordance with 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph. The presumption that the claim limitation is interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is rebutted when the claim limitation recites sufficient structure, material, or acts to entirely perform the recited function.
Absence of the word “means” (or “step”) in a claim creates a rebuttable presumption that the claim limitation is not to be treated in accordance with 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph. The presumption that the claim limitation is not interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is rebutted when the claim limitation recites function without reciting sufficient structure, material or acts to entirely perform the recited function.
Claim limitations in this application that use the word “means” (or “step”) are being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, except as otherwise indicated in an Office action. Conversely, claim limitations in this application that do not use the word “means” (or “step”) are not being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, except as otherwise indicated in an Office action.
Claims 1 and 11 recite limitation “the connector for high content screening (HCS) comprises a base equipped with a fixing means so as to be attached to and detached from a lower end of the well plate and a cover positioned on an upper portion of the well plate to be coupled to the base,” which invokes 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph. However, the written description fails to disclose the corresponding structure, material, or acts for performing the entire claimed function and to clearly link the structure, material, or acts to the function.
The structure of the “connector” is devoid of any structure that performs the function in the claim. Furthermore, the structure described in the specification does not perform the entire function in the claim.
Disclosures found in the specification:
• is “capable of uniformly capturing images in the well plate by including a connector for large-capacity high-speed high content screening (HCS), which supports the well plate to reduce a tolerance when a large-capacity and high-speed image is captured” (specification, page 12, 1st full para.).
• “More specifically, the connector for large-capacity and high-speed high content screening (HCS) includes the base 210 equipped with fixing means 140 and 240 so as to be attached to and detached from a lower end of the well plate 100 and a cover 220 positioned on an upper portion of the well plate 100 to be coupled to the base 210. Moreover, the upper end of the base 210 and the lower end of the well plate 100 are characterized by including fixing means 140 and 240 that can be fixed so as to be attached to and detached from each other. In this case, the base includes a convex part 240 for supporting the well plate 100, and the well plate 100 may include a concave part 140 facing the convex part 240 of the base 210. The well plate 100 may be fixed by the fixing means to uniformly capture images during screening”. (Specification, page 19, lines 4-14).
Therefore, the claim is indefinite and is rejected under 35 U.S.C. 112(b) or pre-AIA 35 U.S.C. 112, second paragraph.
Applicant may:
(a) Amend the claim so that the claim limitation will no longer be interpreted as a limitation under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph;
(b) Amend the written description of the specification such that it expressly recites what structure, material, or acts perform the entire claimed function, without introducing any new matter (35 U.S.C. 132(a)); or
(c) Amend the written description of the specification such that it clearly links the structure, material, or acts disclosed therein to the function recited in the claim, without introducing any new matter (35 U.S.C. 132(a)).
If applicant is of the opinion that the written description of the specification already implicitly or inherently discloses the corresponding structure, material, or acts and clearly links them to the function so that one of ordinary skill in the art would recognize what structure, material, or acts perform the claimed function, applicant should clarify the record by either:
(a) Amending the written description of the specification such that it expressly recites the corresponding structure, material, or acts for performing the claimed function and clearly links or associates the structure, material, or acts to the claimed function, without introducing any new matter (35 U.S.C. 132(a)); or
(b) Stating on the record what the corresponding structure, material, or acts, which are implicitly or inherently set forth in the written description of the specification, perform the claimed function. For more information, see 37 CFR 1.75(d) and MPEP §§ 608.01(o) and 2181.
For purpose of examination, if a corresponding prior art structure holds or maintains the plate in position, this will be interpreted as the fixing means of the instant application.
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1-11 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
As stated supra, Claims 1 and 11 recite a connector comprising a base equipped with “a fixing means so as to be attached to and detached from a lower end of the well plate”, which invokes 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph. However, the written description fails to disclose the corresponding structure, material, or acts for performing the entire claimed function and to clearly link the structure, material, or acts to the function. Therefore, the claim is indefinite and is rejected under 35 U.S.C. 112(b) or pre-AIA 35 U.S.C. 112, second paragraph. For purpose of examination, if a corresponding prior art structure holds or maintains the plate in position, this will be interpreted as the fixing means of the instant application.
Claims 1 and 11 recite the terms “large-capacity,” “high-speed,” and “high content screening”. They are relative terms which render the claims indefinite. The terms “large-capacity,” “high-speed,” and “high content screening” are not defined by the claims, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. It is unclear what capacity is intended to be included in, or excluded from “large-capacity”; what speed is intended to be included in, or excluded from “high-speed”; and what content screening is intended to be included in, or excluded from “high content screening.” As such, the metes and bounds of this claim are unclear. Claims 2-10 are rejected as being dependent from claim 1 and not resolving the ambiguity.
Furthermore, Claim 4 contains the trademark/trade name Matrigel. Where a trademark or trade name is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph. See Ex parte Simpson, 218 USPQ 1020 (Bd. App. 1982). The claim scope is uncertain since the trademark or trade name cannot be used properly to identify any particular material or product. A trademark or trade name is used to identify a source of goods, and not the goods themselves. Thus, a trademark or trade name does not identify or describe the goods associated with the trademark or trade name. In the present case, the trademark/trade name is used to identify/describe a type of extracellular matrix-based hydrogel and, accordingly, the identification/description is indefinite.
Furthermore, Claim 7 recites the phrase “a new anticancer therapeutic”. The term “new” is a relative term which renders the claim indefinite. The term “new” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. It is unclear what anticancer therapeutic is intended to be included in, or excluded from “a new anticancer therapeutic”. As such, the metes and bounds of this claim are unclear.
Claim Rejections - 35 USC § 112(d)
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 2 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 2 recites the limitation that the selecting when the cancer organoid treated with the anticancer agent and/or radiation has a viability ranging from 100 to 70% compared to an organoid before treatment. In other words, the viability after treatment is equal to or less than that before the treatment. However, the base claim 1 recites the selecting when the cancer organoid treated with the anticancer agent and/or radiation has a viability equal to or more than that before the treatment. Thus, the limitation in claim 2 fails to further limit the subject matter of the base claim 1.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Claim Rejections - 35 USC § 112(a)
NEW MATTER
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.
Claim 8 is 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.
The limitations of the sub wells having an upper end diameter ranging from “30 to 45 mm” and the recessed parts having an upper end diameter ranging from “0.45 to 15 mm” in instant claim 8 represent new matter. MPEP 2163.06 notes “If new matter is added to the claims, the examiner should reject the claims under 35 U.S.C. 112(a), pre-AIA first paragraph - written description requirement. In re Rasmussen , 650 F.2d 1212, 211 USPQ 323 (CCPA 1981).” A review of the specification by the Examiner did NOT find any specific basis for the recited range limitation. The range limitations in the specification recite the sub wells may have an upper end diameter ranging from 3.0 to 4.5 mm, the recessed parts may have an upper end diameter ranging from 0.45 to 1.5 mm (see e.g., specification, p. 7, last sentence – p. 8, 1st sentence, and p. 17, para 2). The limitations in claim 8 are examined according to the ranges in the specification.
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.
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.
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 1-5 and 7-11 are rejected under 35 U.S.C. 103 as being unpatentable over Gao et al., (CN108456642, published 8/28/2018, Cited in IDS 03/13/2025. English translation attached) in view of Wang et al., (US 2017/0043337 A1).
With respect to independent claim 1 and claim 11, it is noted that the limitations “providing information necessary for diagnosis of resistance to an anticancer agent and/or radiation" in the preamble of claim 1 and “screening a drug which alleviates the drug resistance of cancer cells” in the preamble of claim 11 are interpreted as intended use. MPEP 2111.02 II states “If the body of a claim fully and intrinsically sets forth all of the limitations of the claimed invention, and the preamble merely states, for example, the purpose or intended use of the invention, rather than any distinct definition of any of the claimed invention's limitations, then the preamble is not considered a limitation and is of no significance to claim construction”. Gao teaches a method for screening cancer cell chemotherapeutic drugs and concentrations (see e.g., abstract), which can be used for providing information necessary for diagnosis of resistance to an anticancer agent, or for screening a drug which alleviates the drug resistance of cancer cells, thus teaches preambles of claims 1 and 11.
In regard to isolating a cancer tissue from a subject with cancer in claims 1 and 11, Gao teaches steps of (1) taking 1.0 cm3 under aseptic condition fresh liver cancer tissue, (2) rinse the liver cancer tissue, (3) cuts the rinsed liver cancer tissue into 1 mm3 blocks, (4) add collagenase to prepare cell suspension (see p. 5, last 4 paragraphs). Thus, Gao teaches isolating a cancer tissue from a subject with cancer.
In regard to culturing the cancer tissue into a cancer organoid in a 3D cell culture plate in claims 1 and 11, Gao teaches culturing the cancer cell suspension in a cell culture plate until the three-dimensional cell pellet reaches the test requirement (see p. 6, the paragraph after the numbered paragraphs and the paragraph S3). It is noted that this “cell pellet” is also referred to as “sphere” (see e.g. p. 1, reference claims 2-5) that is equivalent to the claimed cancer organoid. Gao teaches a “three-dimensional sphere-gathered culture plate” for cancer sphere culture (see e.g., abstract and reference claims 1-5).
In regard to treating the cultured cancer organoid with an anticancer agent in claims 1 and 11, Gao teaches a step “S3: after the three-dimensional cell pellet reaches the test requirement, adding the drug to be tested with a preset concentration gradient into the culture hole” (p. 6, paragraph S3) and teaches a step “S4, after co-culturing with the drug to be detected for a preset time, measuring cell activity indexes to determine the chemotherapeutic drug aiming at the cells and the sensitive concentration of the chemotherapeutic drug” and “the cell activity index measured in this example employs a method of indirectly measuring the number of living cells” (p. 6, paragraph S4 and the following paragraph, see Figs 10-14 for 4 tested drugs). Thus, Gao teaches treating the cultured cancer organoid with an anticancer agent and teaches measuring the number of living cells (i.e., cell viability) after treatment.
In regard to selecting the cancer organoid having resistance to the anticancer agent and/or radiation when the cancer organoid treated with the anticancer agent and/or radiation has a viability equal to or more than that before the treatment in claim 1 and claim 11, and the following steps directed to the selected cancer organoid having resistance to the anticancer agent and/or radiation in claim 11 (including treating the resistant organoid with a candidate material and comparing viability of a group treated with the candidate material and determining the candidate material as a drug for alleviating the drug resistance of cancer cells when the viability in the candidate material group is lower than that of control), MPEP 2111.04 (II) indicates that the broadest reasonable interpretation of a method (or process) claim having contingent limitations requires only those steps that must be performed and does not include steps that are not required to be performed because the condition(s) precedent are not met. In the instant case, the step of selecting the cancer organoid having resistance to the anticancer agent and/or radiation is only required to be performed under the condition when the cancer organoid treated with the anticancer agent and/or radiation has a viability equal to or more than that before the treatment, but this step is not required to be performed when the condition precedent is not met. Thus, this selecting step in claims 1 and 11, and the following steps directed to the selected organoid in claim 11, are not included in claim construction under the broadest reasonable interpretation.
In regard to the 3D cell culture plate comprising 0% of an extracellular matrix-based hydrogel in claims 1 and 11, Gao teaches the cancer tissue is cultured in a complete medium including Williams' E culture medium containing 10% fetal bovine serum, hepatocyte growth factor, epidermal growth factor, dexamethasone, insulin, glutamine and antibiotics (see e.g., p. 6, para. 10), thus teaches the 3D cell culture plate comprising 0% of an extracellular matrix-based hydrogel.
In regard to the 3D cell culture plate comprising a well plate comprising a plurality of main wells and sub wells and recessed parts on a bottom surface in claims 1 and 11, Gao teaches the 3D cell culture plate comprises a well plate that comprises a plurality of wells (see Fig 1 in p. 24). Gao teaches in each of the plurality of wells, there is a main well and a sub well formed at lower portion of the main well into which the cell culture medium is added, and recessed parts on the bottom surface (see modified Fig 2 attached below). Gao teaches the main well has a step formed so as to be tapered at a predetermined site and the step has an inclination angle of about 20° with respect to a wall of the main well (see modified Fig 2 attached below). Gao teaches a cover positioned on an upper portion of the well plate (e.g., abstract and reference claim 1).
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However, Gao is silent on a connector supporting the well plate and comprising a base equipped with a fixing means to attach the base to a lower end of the well plate in claims 1 and 11.
Wang teaches a microplate which allows to carry out a method for determining the result of an agglutination reaction with a high throughput (e.g., [0009]). Wang teaches for carrying out the method for determining the result of an agglutination reaction in an apparatus (see Figs 7-10), there is a connector supporting the well plate (see e.g., Fig 8, item #26 a microplate carrier on the left, see also [0062] and Fig 11 for a close up view of the carrier), which comprises a base (see Fig 11 for at least a base frame) and is equipped with rims (Fig 11, item #42), thus teaches the connector comprises a base equipped with a fixing means (i.e., the rims) so as to attach the connector to the lower end of the well plate to carry the well plate.
Therefore, it would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method for screening cancer cell chemotherapeutic drugs comprising culturing cancer tissue in a 3D cell culture plate comprising a well plate and a cover disclosed by Gao, by combining a connector comprising a base equipped with a fixing means to attach to and detach from the lower end of the well plate to support the well plate as suggested by Wang with a reasonable expectation of success. Since Wang teaches the microplate carrier (i.e., the connector) can support the well plate to be used in an apparatus to carry out the method for a high throughput detection (e.g., [0009] and Figs 7-11), one of ordinary skill in the art would have had a reason to combine a connector comprising a base to support the well plate and the cover in order to enable a high throughput detection assay for screening cancer chemotherapeutic drugs.
With respect to claim 2 directed to a viability range, and claim 3 directed to a size range for selecting the cancer organoid having resistance to the anticancer agent and/or radiation, as stated supra, the step of selecting the cancer organoid having resistance to the anticancer agent and/or radiation is not required to be performed when the recited limitations are not met. Thus, these wherein clauses do not provide any patentable weight in determining patentability of the claimed method. Gao, in view of Wang, make obvious the method of claims 2 and 3 as discussed above.
With respect to claim 4 directed to the 0% of hydrogel in claim 1 being Matrigel, as stated supra, Gao teaches the cancer tissue is cultured in a complete medium that does not include Matrigel (see e.g., p. 6, para. 10), thus teaches the culturing comprises 0% of Matrigel.
With respect to claim 5 directed to the size of the cancer organoids being 300 um in diameter, Gao teaches the third cavity (i.e., the recessed part) has a diameter of 400 um (see e.g., reference claim 7) and teaches the cancer organoids form in the third cavities (see Fig 8 and Fig 9) that have a diameter of about half of that of the cavities (i.e., about 200 um in diameter). Accordingly, it would have been obvious to one of ordinary skill in the art to have cultured the cancer tissue into cancer organoids with a diameter of 300 um since MPEP 2144.05(I) teaches “a prima facie case of obviousness exists where the claimed ranges or amounts do not overlap with the prior art but are merely close. Titanium Metals Corp. of America v. Banner, 778 F.2d 775, 227 USPQ 773 (Fed. Cir. 1985).” Thus, “approaching, similar or close range” is obvious in the absence of any showing of unexpected results or criticality.
With respect to claim 7 directed to the anticancer agent being a cytotoxic anticancer agent, Gao tested anticancer agents including cisplatin, oxaliplatin, gemcitabine and doxorubicin (p. 6, 4th para from the bottom), which are cytotoxic anticancer agents.
With respect to claim 8, Gao teaches the sub well has an inclined surface formed so as to taper toward the recessed part (see the inclined wall of sub well in the modified Fig 2 attached above). Gao teaches the third cavity (i.e., the recessed part) has a diameter of 400 um (see e.g., reference claim 7) and the sub wells have an upper end diameter that is about 8 times of that of the recessed part (measured from the modified Fig 2 attached above), thus have a diameter of about 3.2 mm (it is noted that the range is examined as disclosed in the specification, i.e., from 3.0 to 4.5 mm). The recessed parts have an upper end diameter of 400 um (0.4 mm), which is close to the claimed diameter of 0.45 mm. The inclined surface (θ2) between the sub well and the recessed part is about 50° (see the modified Fig 2 attached above), within the claimed range. The length ratio of the diameter of the sub wells to the diameter of the recessed parts is about 8:1 (see above, i.e., about 1:0.125), within the claimed range.
With respect to claim 9 directed to the volume of the main well and the recessed part, Gao teaches the total volume of the culture wells is greater than or equal to 50 μl (e.g., p. 1, reference claim 5) and teaches an exemplary 48-well plate (one of ordinary skill in the art would have immediately understood that 0.3 mL/well medium is suggested for a 48-well plate) and teaches the number and arrangement of the culture holes (wells) on the three-dimensional pellet culture plate can be adjusted according to the culture requirements (p. 4, Detailed Description, para 2. And the culture volume of the wells would be adjusted accordingly). Gao further teaches the position of the first positioning ring can be adjusted, i.e. adjusting the ratio between the volume of the first cavity (main well) and the sum of the volumes of the second cavity (sub well) and the first diversion hole (the space part) so as to adapt to the needs of different liquid exchange amounts (p. 5, para 2), suggesting the volume of main well and other parts can be adjusted. Therefore, it would have been obvious for one of ordinary skill in the art to have adjusted the culture volume of the culture wells and the recessed parts to arrive at the claimed volume range and ratio as suggested by Gao with a reasonable expectation of success. Since Gao suggests the number of wells (and thus the volume of the wells) in the 3D cell culture plate can be adjusted according to the culture requirements and the volume of the parts can be adjusted to adapt to the needs of different liquid exchange amounts (and thus is a result effective variable), one of ordinary skill in the art would have had a reason to adjust the volume of the main wells and the recessed parts in order to optimize the 3D cell culture plate for their culture needs. Furthermore, it would have been obvious to one having ordinary skill in the art before the filing date of the invention to apply the claimed volumes and ratio, since it has been held that discovering an optimum value of a result effective variable involves only routine skill in the art. In re Boesch, 617 F.2d 272, 205 USPQ 215 (CCPA 1980).
With respect to claim 10, Gao teaches the main well comprises a space part between the step and the sub well (see the modified Fig 2 above). The space part has a height of about 3.5 times of the diameter of the recessed part and the sub well has a height of about 4 times of the diameter of the recessed part (measured from the modified Fig 2 above), thus the space part has a height of about 1.4 mm and the sub well has a height of about 1.6 mm, and the height ratio of the space part to the sub well is about 0.9 : 1, thus teaches the heights and ratio that are within or close to the claimed range. Gao teaches the positions of the first positioning ring and the second positioning ring can be adjusted (i.e., the heights of various parts would be adjusted accordingly) so as to adapt to the needs of different liquid exchange amounts (p. 5, para 2 and p. 7, 2nd last para). Therefore, it would have been obvious for one of ordinary skill in the art to have adjusted the heights and ratio of the space part and the sub well to arrive at the claimed range as suggested by Gao with a reasonable expectation of success. Since Gao suggests the heights of the parts can be adjusted to adapt to the needs of different liquid exchange amounts (and thus is a result effective variable), one of ordinary skill in the art would have had a reason to adjust the heights of the space part and the sub well in order to optimize the 3D cell culture plate for their culture needs. It would also have been obvious to one having ordinary skill in the art before the filing date of the invention to apply the claimed heights and ratio, since it has been held that discovering an optimum value of a result effective variable involves only routine skill in the art. In re Boesch, 617 F.2d 272, 205 USPQ 215 (CCPA 1980).
Hence, the claimed invention as a whole was prima facie obvious to a person of ordinary skill before the effective filing date of the claimed invention in the absence of evidence to the contrary.
Claim 6 is rejected under 35 U.S.C. 103 as being unpatentable over Gao et al., (CN108456642, published 8/28/2018, Cited in IDS 03/13/2025) in view of Wang et al., (US 2017/0043337 A1), as applied to claim 1 above, and further in view of van de Wetering et al., (Cell. 2015; 161: 933-945).
Claim 6 is directed to the cancer being a colorectal cancer.
However, Gao teaches liver cancer tissues, but is silent on a colorectal cancer.
Nevertheless, Gao teaches the method can be applied to drug screening of other cancer cells or malignant proliferation cells (p. 7, the 3rd para. from bottom).
van de Wetering teaches a method of culturing 3D cancer organoids derived from tumor tissue from colorectal cancer patients and a method of using these cancer organoids for a high throughput drug screen (see e.g., cover page, “In Brief” and “Highlights”).
Therefore, it would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method for screening chemotherapeutic drugs using liver cancer organoids suggested by Gao in view of Wang, by substituting the liver cancer organoids with colorectal cancer organoids as suggested by van de Wetering with a reasonable expectation of success. Since van de Wetering teaches colorectal cancer organoids can be used for a high throughput drug screen for personalized therapy design (cover page, “In Brief” and “Highlights”), one of ordinary skill in the art would have had a reason to substitute with colorectal cancer organoids in the method of Gao in view of Wang in order to screen chemotherapeutic drugs for colorectal patients for personalized therapy design.
Hence, the claimed invention as a whole was prima facie obvious to a person of ordinary skill before the effective filing date of the claimed invention in the absence of evidence to the contrary.
Provisional Double Patenting Rejections
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 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.
Claims 1-11 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over copending claims of Applications 18/115,985 (‘985), 17/628,719 (‘719), 17/628,710 (‘710) and 17/629,034 (‘034) in view of Gao et al., (CN108456642, published 8/28/2018, Cited in IDS 03/13/2025) and van de Wetering et al., (Cell. 2015; 161: 933-945). Although the claims at issue are not identical, they are not patentably distinct from each other.
Copending claims in ‘985 recite a well plate comprising repeating pattern of well structures, each of the well structure is continuously provided with a space part in between a main well to be injected with a cell culture solution and a sub well including a recessed part where cells are cultured, the main well is connected to the space part with forming a step, and the sub well is connected to the space part with forming a inclined surface, the step has a inclination angle ranging from 10 to 60°, the inclined surface has an inclination angle ranging f