DETAILED ACTION
Notice of 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 .
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
Withdrawal of Objections and Rejections
Applicant's response, filed 04/10/2026, has been fully considered.
In view of the amendment and remarks from 04/10/2026, the objection to the claims and the rejection of the following claims are withdrawn:
claim 12 under 35 USC § 112(b);
claims 13-15, 18 and 27 under 35 USC § 101;
claims 13-15, 18 and 27 under 35 U.S.C. § 103.
The following rejections and/or objections are either maintained or newly applied for claims 1-12, 16-17, 19-22 and 25. They constitute the complete set applied to the instant application. Herein, "the previous Office action" refers to the Final Rejection of 12/10/2025.
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 04/10/2026 has been entered.
Status of the Claims
Claims 13-15, 18 and 26-27 are canceled.
Claims 1-12, 16-17, 19-25 are pending.
Claims 23-24 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a non-elected species, as set forth in the Non-Final Office Action dated 04/11/2025.
Claims 1-12, 16-17, 19-22 and 25 are examined.
Claims 1-12, 16-17, 19-22 and 25 are rejected.
Priority
This application is a 371 of PCT/EP2019/084195 (12/09/2019) which claims priority from Foreign Application No. EP18211231.8 (12/10/2018) as reflected in the filing receipt mailed on 01/25/2022. The claims to the benefit of priority are acknowledged and the effective filing date of claims 1-12, 16-17, 19-22 and 25 is 12/10/2018.
Claim objections
Claim 2 is objected to because of the following an informality related to grammar: the recited “with comprising” where "with" should be deleted. Appropriate correction is required.
Claim Rejections - 35 USC § 112(b)
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.
Claims 1-12, 16-17, 19-22 and 25 are rejected under 35 U.S.C. 112(b)as being indefinite for failing to particularly point out and distinctly claim the subject matter the invention. Dependent claims are rejected similarly, unless otherwise noted below. Any newly recited portions are necessitated by claim amendment. The following issues cause the respective claims to be rejected under 112(b) as indefinite:
Claim 1 recites "(B) the docking space of the non-wild-type protein is defined based on a 3D homology-model of a corresponding wild-type or homolog protein" which is indefinite because it is unclear whether the wherein clause actively requires "defining" the docking space or if it should be interpreted as a product by process claim element only further limiting the type of data utilized in the invention such that actively "defining" the docking space is not required within the metes and bounds of the invention. As set forth in MPEP 2111.04.I, “wherein” clauses raise the question as to the limiting effect of the language in a claim. As the claims do not recite an active performance of steps, the metes and bounds of the claims are unclear. For compact examination, it is assumed that the "defining" the docking space is not required to be performed. The rejection may be overcome by clarifying what steps are required to be performed.
The following recitations require but lack antecedent basis, rendering their claims indefinite because there is no previous recitations of the followings terms as written:
claim 2 , "the amino acid sequence" (step iii)
claim 2 , "the expression product" (step iii)
claims 9-10 , "the binding affinity"
Claim 12 recites “a docking space” which presents an unclear relationship with the recited "a docking space" in claim 1. It is unclear if the recited are referring to the same docking space of different ones. The examiner suggests amending claim 12 to “the docking space” to overcome the rejection.
In claim 19, the recited "high pharmacologic activity in antineoplastic treatment" (line 3) is a term of relative or vague degree or form of association, neither defined in the specification (pg. 24 line 14) nor having a well-known and sufficiently particular definition in the art and in the instant context. The disclosure at pg. 24 line 14 is not interpreted as a definition. (MPEP 2173.05(b) pertains.) Although claims are interpreted in light of the specification, examples from the specification are not imported into the claims as limitations absent a clearly limiting definition in the specification. (MPEP 2173.05(b) pertains.)
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 1-12, 16-17, 19-22 and 25 are rejected under 35 USC § 101 because the claimed inventions are directed to one or more Judicial Exceptions (JEs) without significantly more. Regarding JEs, "Claims directed to nothing more than abstract ideas..., natural phenomena, and laws of nature are not eligible for patent protection" (MPEP 2106.04 §I). Abstract ideas include mathematical concepts and procedures for evaluating, analyzing or organizing information, which are a type of mental process (MPEP 2106.04(a)(2)). Any newly recited portions are necessitated by claim amendment.
101 background
MPEP 2106 organizes JE analysis into Steps 1, 2A (Prong One & Prong Two), and 2B as analyzed below. MPEP 2106 and the following USPTO website provide further explanation and case law citations: uspto.gov/patent/laws-and-regulations/examination-policy/examination-guidance-and-training-materials.
Step 1: Are the claims directed to a process, machine, manufacture, or composition of matter (MPEP 2106.03)?
Step 2A, Prong One: Do the claims recite a judicially recognized exception, i.e., a law of nature, a natural phenomenon, or an abstract idea (MPEP 2106.04(a-c))?
Step 2A, Prong Two: If the claims recite a judicial exception under Prong One, then is the judicial exception integrated into a practical application by an additional element (MPEP 2106.04(d))?
Step 2B: Do the claims recite a non-conventional arrangement of elements in addition to any identified judicial exception(s) (MPEP 2106.05)?
Analysis of instant claims
Step 1: Are the claims directed to a 101 process, machine, manufacture, or composition of matter (MPEP 2106.03)?
The instant claims are directed to a method (claims 1-12, 16-17 and 19-22) and a CRM (claim 25); each of which falls within one of the categories of statutory subject matter.
[Step 1: claims 1-12, 16-17, 19-22 and 25: Yes]
Step 2A, Prong One: Do the claims recite a judicially recognized exception, i.e., a law of nature, a natural phenomenon, or an abstract idea (MPEP 2106.04(a-c))?
Background
With respect to Step 2A, Prong One, the claims recite judicial exceptions in the form of abstract ideas. MPEP § 2106.04(a)(2) further explains that abstract ideas are defined as:
• mathematical concepts (mathematical formulas or equations, mathematical relationships
and mathematical calculations) (MPEP 2106.04(a)(2)(I));
• certain methods of organizing human activity (fundamental economic principles or practices, managing personal behavior or relationships or interactions between people) (MPEP 2106.04(a)(2)(II)); and/or
• mental processes (concepts practically performed in the human mind, including observations, evaluations, judgments, and opinions) (MPEP 2106.04(a)(2)(III)).
Analysis of instant claims
With respect to the instant claims, under the Step 2A, Prong One evaluation, the claims are found to recite abstract ideas that fall into the grouping of mathematical concepts (in particular mathematical relationships and formulas) and mental processes (in particular procedures for observing, analyzing and organizing information) as well as a law of nature or a natural phenomenon are as follows.
Mathematical concepts (in particular mathematical relationships and formulas) include:
• "(iv) fitting the 3D structure of the compound with the docking space of step (iii)" (claim 2);
• "(v) determining the binding affinity of the compound to the docking space " (claim 9);
• " (b) fitting each 3D structure of a compound with the one or more docking spaces in a manner that the 3D structure of the compound can rotate and scans over each docking space" (claim 9);
• " (c) determining the binding energy between each compound and each docking space at each grid point and calculating binding affinity for each compound at each 3D orientation with each docking space" (claim 9);
• " (d) determining the lowest binding affinity for each compound-protein interaction" (claim 9);
• " (vi) identifying one or more compounds specifically binding to the mutated protein" (claim 9);
• " fitting the compounds with these one or more docking spaces; determining the lowest binding energy of each compound to these one or more docking spaces" (claim 10); and
• "determining the binding affinity" (claim 10).
The claims identified above read on math. The abstract ideas recited in the claims are evaluated under the Broadest Reasonable Interpretation and determined each element performed either in the mind and/or by mathematical operation. Without further detail as to the methodology involved in "determining binding affinities using docked spaces", under the BRI, one may simply, for example, use pen and paper to perform mathematical steps to arrive at the described steps. Further support for the mathematical techniques used in the claims is provided in the specification at pg. 36 lines 22-25 which discloses "binding energies and the number of conformations in each cluster attained from the docking files with the corresponding lowest binding energies and mean values being calculated." Thus, the recited terms correspond to verbal equivalents of mathematical concepts because they constitute actions executed by a group of mathematical steps in a form of a mathematical algorithm; thus mathematical concepts (MPEP 2106.04(a)(2)). A mathematical concept need not be expressed in mathematical symbols, because "words used in a claim operating on data to solve a problem can serve the same purpose as a formula." In re Grams, 888 F.2d 835, 837 and n.1, 12 USPQ2d 1824, 1826 and n.1 (Fed. Cir. 1989). MPEP 2106.04(a)(2) pertains.
Mental processes, defined as concepts or steps practically performed in the human mind such as steps of observations, evaluations, judgments, analysis, opinions or organizing information include:
• "(C) the method comprises … to screen a database of 3D structures of chemical compounds to select for a compound fitting the docking space of the non-wild-type protein" (independent claim 1);
• "(iii) (a) adapting the amino acid sequence of the 3D structure of the wild-type or homolog protein of step (ii) to the expression product of the mutated gene identified in step (i) " (claim 2);
• "defining the docking space of the obtained 3D structure of mutated protein, or (b) defining the docking space of the 3D structure of the wild-type or homolog protein of step (ii) and adapting the amino acid sequence of the docking space to the expression product of the mutated gene identified in step (i)" (claim 2);
• "defining one or more docking spaces of the structure of the wild-type or homolog protein of step (ii) each corresponding to the respective docking spaces of the structure of the mutated protein of step (iii)" (claim 10);
• "comparing the binding affinity of each compound to the docking spaces of the mutated and of the wild-type or homolog protein" (claim 10);
• "identifying one or more compounds having a higher binding affinity to the docking space of the wild-type or homolog protein than to the corresponding docking space of the mutated protein" (claim 10);
• "(vii) of determining toxicological and pharmacologic properties of the compounds identified in step (vi) from one or more databases" (claim 19);
• "identifying a compound of comparably low toxicity and, high pharmacologic activity in antineoplastic treatment" (claim 19); and
• "identifying an antineoplastic agent which has antineoplastic activity against the neoplasm, wherein said antineoplastic agent is or comprises one or more compounds identified in any of steps (vi) or (vii)" (claim 20).
Under the BRI, the recited limitations are mental processes because a human mind is also sufficiently capable of screen a database to select a compound, adapt an amino acid sequence, define a docking space based on data evaluation, compare binding affinities and identify a compound with higher affinity, determine toxicological and pharmacologic properties based on data evaluation and identify an antineoplastic agent based on data evaluation.
Dependent claims 5-8, 12 and 21-22 recite further steps that limit the judicial exceptions in independent claim 1 and, as such, also are directed to those abstract ideas. For example, claims 5-6 and 8 recite further details about the database of 3D structures; claim 7 recites further details about steps (iii) to (iv); claim 12 recites further details about the docking space used for the fitting calculations; and claims 21-22 recite further details about the chemical compounds fitted during calculations. Steps A and B in claim 1 further limit the protein and the docking space used in the fitting calculations, not constituting active steps.
Furthermore, the instant claims recite a natural correlation by correlating a protein naturally found in the body to its binding affinity to a candidate chemical compound. (see MPEP 2106.04(b).I).
[Step 2A Prong One: claims 1-12, 16-17, 19-22 and 25: Yes ]
Step 2A, Prong Two: If the claims recite a judicial exception under Prong One, then is the judicial exception integrated into a practical application by an additional element (MPEP 2106.04(d))?
Background
MPEP 2106.04(d).I lists the following example considerations for evaluating whether a judicial exception is integrated into a practical application:
An improvement in the functioning of a computer or an improvement to other technology or another 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).
Analysis of instant claims
Instant claims 1-2 and 25 recite additional elements that are not abstract ideas:
• "using an unbiased software program" (independent claim 1);
• "(ii) providing a three-dimensional (3D) structure of a wild-type or homolog protein expressed by a wild-type or homolog gene corresponding to the mutated gene identified in step (i) " (claim 2);
• "(i) identifying a mutated gene transcribing the mRNA transcript by: (a) providing a sample from the diseased tissue or bodily fluid containing the mRNA transcript" (claim 2);
• "(b) generating cDNA from the mRNA transcript by a polymerase chain reaction and identifying the at least one mutation by at least one of the following steps: sequencing the mRNA and/or the cDNA generated from the mRNA by a polymerase chain reaction; hybridizing the mRNA and/or the cDNA generated from the mRNA by a polymerase chain reaction with a chip containing a variety of single-stranded nucleotides embracing mutated and non-mutated sequences; and conducting a polymerase chain reaction with comprising primers specific for at least one mutation" (claim 2);
• " (a) generating a 3D grid box of docking space of the mutated protein and of each compound, wherein each grid box comprises grid points defined in all three dimensions that provide pieces of information selected from the group consisting of charges, partial charges, the ability to form hydrogen bonds, the ability to form pi-pi-electron interactions, and the ability to form van-der-Waals forces" (claim 9); and
• "computer program stored on anon-transitory computer readable medium, the computer program comprising instructions which, when the program is executed by a computer, cause the computer to carry out the method of claim 1" (independent claim 25).
Dependent claims 3 and 16-17 recite further details about the diseased cell or tissue. Dependent claim 11 recites further details about the software program. Dependent claim 4 recites further details about the mRNA transcripts.
Considerations under Step 2A, Prong Two
The recited limitations in claims 1-2 and 25 are interpreted as requiring the use of a computer.. Hence, the claims explicitly recite steps executed by computers and therefore can be described as computer functions or instructions to implement on a generic computer.
Further steps directed to additional non-abstract elements of a computing device/computer do not describe any specific computational steps by which the "computer parts" perform or carry out the judicial exceptions, nor do they provide any details of how specific structures of the computer are used to implement these functions. The claims state nothing more than a generic computer which performs the functions that constitute the judicial exceptions. The instant claims state nothing more than that a generic computer performs the functions that constitute the abstract idea (MPEP 2106.05(f)).
The judicial exceptions in the claims are considered to perform the claimed abstract idea with a computer, which is not sufficient to integrate an abstract idea into a practical application (see MPEP 2106.05(f)); since steps that can be performed mentally and merely performing the mental process in a computer environment do not negate the fact that something that can be carried out in the human mind. See MPEP 2106.04(a)(2).III.C.
Claims reciting “providing a 3D structure” (claim 1) and "generating a 3D grid box" (claim 9) read on gathering data necessary to guide the “computer-assisted” method in identifying one or more compounds specifically binding to a target structure of a given diseased tissue. Thus, the recited additional elements, alone or in combination with the judicial exceptions, do not appear to provide an inventive concept. These additional elements appear to be insignificant extra-solution activity (MPEP 2106.05(g) because they merely serve as necessary data gathering/outputting and do not amount to a practical application.
Claim 2 recites "providing a sample …" which constitutes data gathering activity because the step is utilized to gather information. Claim 2 recites "(b) generating cDNA from the mRNA transcript by a polymerase chain reaction and identifying the at least one mutation by at least one of the following steps: sequencing the mRNA and/or the cDNA generated from the mRNA by a polymerase chain reaction; hybridizing the mRNA and/or the cDNA generated from the mRNA by a polymerase chain reaction with a chip containing a variety of single-stranded nucleotides embracing mutated and non-mutated sequences; and conducting a polymerase chain reaction with comprising primers specific for at least one mutation" which reads on detecting DNA in a patient sample, being an insignificant extra-solution activity since this limitation serve to gather data that is utilized as input for the judicial exception. See MPEP 2106.05(g) and MPEP 2106.04(d).
Hence, these are mere instructions to apply the abstract idea using a computer and insignificant extra-solution activity and therefore the claims do not integrate that abstract idea into a practical application (see MPEP 2106.04(d) § I; 2106.05(f); and 2106.05(g)).
In Step 2A, Prong One above, claim steps and/or elements were identified as part of one or more judicial exceptions (JEs).
In this Step 2A, Prong Two immediately above claim steps and/or elements were identified as part of one or more additional elements. Additional elements are further discussed in Step 2B below.
Here in Step 2A, Prong Two, no additional step or element clearly demonstrates integration of the JE(s) into a practical application.
[Step 2A Prong Two: claims 1-12, 16-17, 19-22 and 25: No]
Step 2B: Do the claims recite a non-conventional arrangement of elements in addition to any identified judicial exception(s) (MPEP 2106.05)?
According to analysis so far, the additional elements described above do not provide significantly more than the judicial exception. A determination of whether additional elements provide significantly more also rests on whether the additional elements or a combination of elements represents other than what is well-understood, routine, and conventional. Conventionality is a question of fact and may be evidenced as: a citation to an express statement in the specification or to a statement made by an applicant during examination that demonstrates a well-understood, routine or conventional nature of the additional element(s); a citation to one or more of the court decisions as discussed in MPEP 2106(d)(II) as noting the well-understood, routine, conventional nature of the additional element(s); a citation to a publication that demonstrates the well-understood, routine, conventional nature of the additional element(s); and/or a statement that the examiner is taking official notice with respect to the well-understood, routine, conventional nature of the additional element(s).
Claims 1-2 and 25, and claims dependent therefrom, recite a computer or computer functions, interpreted as instructions to apply the abstract idea using a computer, where the computer does not impose meaningful limitations on the judicial exceptions; which can be performed without the use of a computer (MPEP 2106.04(d) § I; and MPEP 2106.05(f)).
With respect to the instant claims, the prior art review to Pagadala (“Software for molecular docking: a review” Biophys. Rev. 9:91–102 (2017); disclosed in the 04/11/2025 Form PTO-892) discloses that the use of molecular docking to explores 3D spaces and the behavior of compounds in the binding site of a target is routine, well-understood and conventional in the art. Said portions of the prior art are, for example, pg. 92 col. 2 para. 3.
Additionally, the instant specification recites that “model evaluation was done with the help several tools (Anolea, GROMOS, QMEAN, DFIRE etc.)” (pg. 35 lines 14-15), which reveals the use of known commercially available software that assist with docking exercise; demonstrating the well-understood, routine, conventional nature of additional elements. See MPEP 2106.07(a).III(A).
When the claims are considered as a whole, they do not integrate the abstract idea into a practical application; they do not confine the use of the abstract idea to a particular technology; they do not solve a problem rooted in or arising from the use of a particular technology; they do not improve a technology by allowing the technology to perform a function that it previously was not capable of performing; and they do not provide any limitations beyond generally linking the use of the abstract idea to a broad technological environment. See MPEP 2106.05(a) and 2106.05(h).
The instant claims constitute insignificant extra solution activity, and when considered individually, are insufficient to constitute inventive concepts that would render the claims significantly more than an abstract idea (see MPEP 2106.05(g)). Hence, these elements, when considered individually, are insufficient to constitute inventive concepts that would render the claims significantly more than an abstract idea (see MPEP 2106.05(d)).
[Step 2B: claims 1-12, 16-17, 19-22 and 25: No]
Conclusion: Instant claims are directed to non-statutory subject matter
For the reasons above, the claims in this instant application, when the limitations are considered individually and as a whole, are directed to an abstract idea and lack an inventive concept not clearly anything significantly more.
Response to applicant's remarks in regard to Claim Rejection 35 U.S.C. ~ 101
The Remarks of 04/10/2026 have been fully considered but are not persuasive for the reasons below:
It appears that pg. 10 para. 2 represents the only Applicant remarks specific to 101 and the instant claims (emphasis added):
Additionally, the limitation pertaining to the docking space of non-wild-type protein, encoded by an mRNA transcript comprising at least one mutation obtained from at least one diseased cell of a diseased tissue or bodily fluid of an individual patient, amounts to significantly more than the judicial exception to patentable subject matter, because this feature is unconventional in the art (see remarks addressing the rejections under§ 103 below).
It is respectfully submitted that this is not persuasive because claim 1 recites a judicial exception – "(C) the method comprises using an unbiased software program to screen a database of 3D structures of chemical compounds to select for a compound fitting the docking space of the non-wild-type protein." Under the BRI, the recited limitation is a mental processes because a human mind is also sufficiently capable of screen a database to select for a compound fitting the docking space of the non-wild-type protein. Said recitation is considered to perform the claimed abstract idea with a computer, which is not sufficient to integrate an abstract idea into a practical application (see MPEP 2106.05(f)); since steps that can be performed mentally and merely performing the mental process in a computer environment do not negate the fact that something that can be carried out in the human mind. See MPEP 2106.04(a)(2).III.C.
Regarding the argument directed to this claimed invention amounting to significantly more than the judicial exception to patentable subject matter, because this feature is unconventional in the art (see remarks addressing the rejections under§ 103 below); the Applicant is reminded that the standard for assessing the conventionality of the additional elements at Step 2B of the 35 USC 101 analysis is separate and distinct from the standard for applying prior art under 35 USC 102 or 103 (see MPEP 2106.05(I)). Because they are separate and distinct requirements from eligibility, patentability of the claimed invention under 35 U.S.C. 102 and 103 with respect to the prior art is neither required for, nor a guarantee of, patent eligibility under 35 U.S.C. 101.
MPEP 2106.05(d) sets forth that, at Step 2B, it is the additional elements which are examined to determine whether they are well-understood, routine, conventional activities previously known to the industry. The analysis at Step 2A, Prong 2, considers the claims as a whole, i.e., the additional elements in combination with the judicial exceptions (see MPEP 2106.05(a)), although the integration or improvement provided in the claim must flow from the additional elements and not the judicial exceptions to be considered persuasive. However, Step 2B instructs that an inventive concept cannot be provided the by judicial exception. An “inventive concept” is furnished by an element or combination of elements that is recited in the claim in addition to (beyond) the judicial exception, and is sufficient to ensure that the claim as a whole amounts to significantly more than the judicial exception itself (Alice Corp., 573 U.S. at 27-18, 110 USPQ2d at 1981 (citing Mayo, 566 U.S. at 72-73, 101 USPQ2d at 1966)). Here. The additional elements read on data gathering or mere instructions to apply the abstract idea using a computer and insignificant extra-solution activity and therefore the claims do not integrate that abstract idea into a practical application (see MPEP 2106.04(d) § I; 2106.05(f); and 2106.05(g)).
Claim Rejections - 35 USC § 103
The following is a quotation of pre-AIA 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter 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 pre-AIA 35 U.S.C. 103(a) 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.
A. Claims 1, 3-5, 8, 11-12, 16-17 and 21-22 are rejected under 35 U.S.C. 103(a) as being unpatentable over Niu (“Protein-structure-guided discovery of functional mutations across 19 cancer types” Nature Genetics 48:827–837 (2016)) as evidenced by Tomczak ("Review The Cancer Genome Atlas (TCGA): an immeasurable source of knowledge." Contemporary Oncology/Współczesna Onkologia 2015(1):68-77 (2015)) in view of Pagadala (“Software for molecular docking: a review” Biophys. Rev. 9:91–102 (2017)), as cited on the 04/11/2025 Form PTO-892. Any newly recited portions are necessitated by claim amendment. Claims 16-17 are additionally evidenced by Dees (“MuSiC: identifying mutational significance in cancer genomes” Genome Res. 22:1589–1598 (2012)). Claim 11 is additionally evidenced by Osterberg (“Automated Docking to Multiple Target Structures: Incorporation of Protein Mobility and Structural Water Heterogeneity in AutoDock” PROTEINS: Structure, Function, and Genetics 46:34-40 (2002)).
Claim 1 discloses a method for screening a candidate chemical compound for binding to a docking space of a non-wild-type protein. Claim 25 discloses a computer program stored on anon-transitory computer readable medium, the computer program comprising instructions which, when the program is executed by a computer, cause the computer to carry out the method of claim1. Niu teaches the use of a server runs on a Dell PowerEdge M620 blade server with one 8-core Intel Xeon E-2603 1.8-GHz CPU and 128 GB of RAM, reading on claim 25.
Claim 1 recites:
the non-wild-type protein is encoded by an mRNA transcript from a diseased cell of a diseased tissue or a bodily fluid of an individual patient, wherein the mRNA transcript comprises at least one mutation as compared to the mRNA transcript of the corresponding wild-type protein;
(B) the docking space of the non-wild-type protein is defined based on a 3D homology-model of a corresponding wild-type or homolog protein; and
(C) the method comprises using an unbiased software program to screen a database of 3D structures of chemical compounds to select for a compound fitting the docking space of the non-wild-type protein
• Niu teaches a computational tool HotSpot3D that identifies mutation–mutation and mutation–drug clusters using three-dimensional protein structures and correlates these clusters with known or potentially interacting functional variants, domains, and proteins (pg. 827 col. 2 para. 3) to map and visualize variants on protein structures (i.e. non-wild type protein) (pg. 827 col. 2 para. 2); wherein each gene analyzed has an ID, transcript, protein ID, sequence and region of interest (i.e. wherein the mRNA transcript comprises at least one mutation as compared to the mRNA transcript of the corresponding wild-type protein – see interpretation in the last line of this instant para.) (col. 1 para. 3 Online Methods) to identify potential intramolecular, intermolecular, and variant–drug interactions near a drug-binding pocket in samples from 19 major cancer types (i.e. from a diseased cell of a diseased tissue or a bodily fluid of an individual patient) (pg. 828 col. 1 para. 2); wherein annotated gene variants are aligned and mapped onto appropriate wild type Protein Database three-dimensional protein structures (pg.82 Fig 1a) with the 3D structure of the gene variant clusters being visualized after structural analysis of variants interactions (pg. 828 Fig. 1a) and compounds interacting with unique variants (i.e. (C) the method comprises using an unbiased software program to screen a database of 3D structures of chemical compounds) (pg. 836 col. 1 para. 2). It is interpreted that any gene that represents a protein expression product is inherently related to an mRNA transcript as evidenced by Tomczak (pg. A70 Table 1).
• Niu does not teach step (B) and "select for a compound fitting the docking space of the non-wild-type protein" in step (C). However, Pagadala teaches computational tools for molecular docking methods wherein docking algorithms predict the binding mode and binding affinity of a molecule to a binding pocket and also relative to other compounds (pg. 92 col. 1 para. 2); wherein docking against homology modeled targets are possible for proteins whose structures are not known (pg. 91 Abstract); wherein the reviewed structure-based drug design is a powerful technique for the rapid identification of small molecules against homology models (pg. 98 col. 2 para. 3).
Claim 3 recites:
wherein the diseased tissue is a neoplasm
• Niu teaches a computational tool HotSpot3D that identifies mutation–mutation and mutation–drug clusters using three-dimensional protein structures and correlates these clusters with known or potentially interacting functional variants, domains, and proteins (pg. 827 col. 2 para. 3) to identify potential intramolecular, intermolecular, and variant–drug interactions near a drug-binding pocket in samples from 19 major cancer types (pg. 828 col. 1 para. 2).
Claim 4 recites:
wherein the RNA transcript, the non-wild-type protein, or both are associated with the onset or progression of a neoplasm
• Niu teaches a computational tool HotSpot3D that identifies mutation–mutation and mutation–drug clusters using three-dimensional protein structures and correlates these clusters with known or potentially interacting functional variants, domains, and proteins (pg. 827 col. 2 para. 3); wherein clusters with all cancer-related proteins were distinguished (i.e. non-wild type protein associated with the onset or progression of a neoplasm) (Online Methods – pg. 2 col. 1 para. 3).
Claim 5 recites:
wherein the database of 3D structures comprises 3D structures of at least five chemical compounds
• Niu teaches a computational tool HotSpot3D that identifies mutation–mutation and mutation–drug clusters using three-dimensional protein structures and correlates these clusters with known or potentially interacting functional variants, domains, and proteins (pg. 827 col. 2 para. 3); wherein annotated gene variants are aligned and mapped onto appropriate wild type Protein Database three-dimensional protein structures (pg.82 Fig 1a) with the 3D structure of the gene variant clusters being visualized after structural analysis of variants interactions (pg. 828 Fig. 1a) and four unique variants interacting with five different compounds: raloxifene, estradiol, estrone, estriol, and diethylstilbestrol as seen via the 3D structure in Figure 7e (pg. 836 col. 1 para. 2).
Claim 8 recites:
wherein the chemical compounds in the database of 3D structures:
have a molecular weight of not more than 1000 Da
are not approved as an antineoplastic agents,
have known pharmacokinetic properties, and/or
are approved for one or more pharmaceutical purposes other than antineoplastic activity
• Niu teaches three-dimensional structures displaying gene variant–drug clusters interactions near the drug-binding pocket suggesting the binding of a list of cancer related compounds to gene variant regions – such as BRAF gene and sorafenib drug (465 Da) (i.e. have a molecular weight of not more than 1000 Da) (pg. 834 Fig. 7c), EGFR gene and lapatinib drug (581 Da) (i.e. have a molecular weight of not more than 1000 Da) (pg. 834 Fig. 7d), and ESR1 gene and raloxifene drug (510 Da) (i.e. have a molecular weight of not more than 1000 Da) (Fig. 7e), wherein said compounds are all approved for pharmaceutical purposes (pg. 835 Table 1).
Claim 11 recites:
wherein using the unbiased software program comprises using a Lamarckian Genetic Algorithm.
• Niu does not teach the recitation above. However, Pagadala teaches computational tools for molecular docking methods using AutoDock as an open-source docking program to predict binding affinity and the orientation of the ligand when it is bound to a protein receptor or enzyme using shape and electrostatic interactions to quantify it (pg. 91 col. 2 para. 1); wherein Lamarckian Genetic Algorithm is an algorithm incorporated in the AutoDock software as evidenced by Osterberg (pg. 37 col. 1 para. 1).
Claim 12 recites:
wherein a docking space embraces the whole protein, the surface of the protein the surface of the protein, the surface of the protein and one or more potential binding pockets or only the surrounding area of the pharmacophore binding site
• Niu does not teach the recitation above. However, Pagadala teaches computational tools for molecular docking methods wherein docking algorithms produce a large number of docked conformations with favorable surface complementarity, followed by the reranking of the conformations using the free energy of approximation. (pg. 92 col. 2 para. 3) and predict binding poses most likely to occur on the broad surface regions and then define the sites into high-affinity complex structures (pg. 99 col. 1 para. 2).
Claim 16 recites:
wherein the diseased cell bears one or more genetic variations selected from the group consisting of one or more mutations, one or more different alleles, one or more polymorphisms, or combinations of two or more thereof, in comparison to corresponding healthy tissue
Claim 17 recites:
wherein the diseased cell bears one or more mutations associated with the disease state of the diseased tissue in comparison to corresponding healthy tissue
• Niu teaches a computational tool that analyzes somatic mutations from TCGA tumor samples from 19 cancer types (Online Methods – pg. 1 col. 2 para. 4); wherein the Cancer Genome Atlas (TCGA) is a program that provided statistically supported lists of significantly mutated genes, therapeutically targetable copy number amplifications in several genes, evidence of overlaps between DNA methylation clusters and gene expression subtypes (i.e. reading on one or more mutations in comparison to corresponding healthy tissue as in claims 16-17) (as evidenced by Dees pg. 1589 col. 2 para. 2).
Claim 21 recites:
wherein the chemical compounds are approved for one or more pharmaceutical purposes
Claim 22 recites:
wherein the chemical compounds are approved for one or more pharmaceutical purposes other than antineoplastic activity and are not approved as antineoplastic agents.
• Niu teaches three-dimensional structures displaying gene variant–drug clusters interactions near the drug-binding pocket suggesting the binding of a list of cancer related compounds to gene variant regions ( pg. 834 Fig. 7); wherein said compounds are all approved for pharmaceutical purposes (pg. 835 Table 1) – including purposes other than antineoplastic activity – hence not approved as antineoplastic agents (i.e. antiasthmatics and antiallergics – not approved as antineoplastic agents pg. 835 Table 1).
Rationale for combining (MPEP §2142-2143)
Regarding claims 1, 3-5, 8, 11-12, 16-17 and 21-22, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine, in the course of routine experimentation and with a reasonable expectation of success, the methods of Niu in view of Pagadala because all references disclose methods for investigation of interactions between a compound and a target structure. The motivation would have been to use a computational tool to obtain rapid identification of small molecules against the 3D structure of the macromolecular targets available by either X-ray, NMR, or homology models (pg. 98 col. 2 para. 3 Pagadala). Therefore it would have been obvious to one of ordinary skill in the art to substitute the investigation of interactions between a compound and a target structure of Niu to the methods by Pagadala because such a substitution is no more than the simple substitution of one known element for another. One of ordinary skill in the art would be able to motivated to combine the teachings in these references with a reasonable expectation of success since the described teachings pertain to methods for investigation of interactions between a compound and a target structure.
B. Claims 2, 6-7 and 9-10 are rejected under 35 U.S.C. 103(a) as being unpatentable over Niu as evidenced by Tomczak in view of Pagadala as applied to claim 1 above further in view of Niu in view of Jordan (“Large-scale expression measurement by hybridization methods: from high-density membranes to “DNA chips” The journal of biochemistry 124(2):251-258 (1998)), as cited on the 04/11/2025 Form PTO-892. Any newly recited portions are necessitated by claim amendment. Claim 6 is additionally evidenced by Berman (“The Protein Data Bank” Nucleic Acids Res. 28:235–242 (2000))
Claim 2 recites:
(i) identifying a mutated gene transcribing the mRNA transcript by:
(a) providing a sample from the diseased tissue or bodily fluid containing the mRNA transcript; and
(b) generating cDNA from the mRNA transcript by a polymerase chain reaction and identifying the at least one mutation by at least one of the following steps:
sequencing the mRNA and/or the cDNA generated from the mRNA by a polymerase chain reaction;
hybridizing the mRNA and/or the cDNA generated from the mRNA by a polymerase chain reaction with a chip containing a variety of single-stranded nucleotides embracing mutated and non-mutated sequences; and
conducting a polymerase chain reaction with comprising primers specific for at least one mutation;
• Niu does not teach the recitation above. However, Jordan teaches methods for large scale measurements of gene expression (i.e. embracing non-mutated sequences) (pg. 251 col. 2 para. 2) and mutation detection (i.e. embracing mutated sequences) comprising DNA chips (i.e. chip containing a variety of single-stranded nucleotides embracing mutated and non-mutated sequences) (pg. 251 Abstract); wherein microarrays are hybridized with probes in which cDNA copy of the mRNA mixture has been labeled (i.e. hybridizing the mRNA and/or the cDNA generated from the mRNA) (pg. 255 col. 2 para. 2); wherein large sets of targets (clones, inserts, oligonucleotides) are hybridized with labeled complex probes prepared from total cell or organ mRNA for mutation detection (i.e. (i) identifying a mutated gene transcribing the mRNA transcript by (a) providing a sample from the diseased tissue or bodily fluid containing the mRNA transcript) (pg. 251 Abstract); wherein probes are prepared from mRNA or total RNA by reverse transcription and labeling of the isolated cDNA by random priming (i.e. (b) generating cDNA from the mRNA transcript by a polymerase chain reaction) (pg. 253 col. 2 para. 2) with Fig. 2 depicting examples of multiple probing comprising cDNA clones inserts (i.e. conducting a polymerase chain reaction with comprising primers specific for at least one mutation) (pg. 254); wherein a labeled complex probe is hybridized with an array consisting of many DNA targets, each representing a particular gene and the targets can be either processed bacterial colonies, PCR products from cDNA clones sets of synthetic oligonucleotides designed to assay a particular gene with the combination of a complex probe containing many different mRNA species with a large array (i.e. sequencing the mRNA and/or the cDNA generated from the mRNA by a polymerase chain reaction) (pg. 252 col. 1 para. 3).
(ii) providing a three-dimensional (3D) structure of a wild-type or homolog protein expressed by a wild-type or homolog gene corresponding to the mutated gene identified in step (i);
(iii) (a) adapting the amino acid sequence of the 3D structure of the wild-type or homolog protein of step (ii) to the expression product of the mutated gene identified in step (i) and defining the docking space of the obtained 3D structure of mutated protein, or
(b) defining the docking space of the 3D structure of the wild-type or homolog protein of step (ii) and adapting the amino acid sequence of the docking space to the expression product of the mutated gene identified in step (i); and
• Niu teaches annotated gene variants aligned and mapped onto appropriate wild type Protein Database three-dimensional protein structures (pg.82 Fig 1a) (i.e. (ii) providing a three-dimensional (3D) structure of a wild-type or homolog protein expressed by a wild-type or homolog gene corresponding to the mutated gene identified in step (i) … (a) adapting the amino acid sequence of the 3D structure of the wild-type or homolog protein of step (ii) to the expression product of the mutated gene identified in step (i)) with the 3D structure of the gene variant clusters (i.e. reading on expression product of the mutated gene) being visualized after structural analysis of variants interactions (i.e. (b) defining the docking space of the 3D structure of the wild-type or homolog protein of step (ii) and adapting the amino acid sequence of the docking space to the expression product of the mutated gene identified in step (i)) (pg. 828 Fig. 1a).
(iv) fitting the 3D structure of the compound with the docking space of step (iii)
• Niu does not teach the recitation above. However, Pagadala teaches computational tools for molecular docking methods wherein docking algorithms predict the binding mode and binding affinity of a molecule to a binding pocket and also relative to other compounds (pg. 92 col. 1 para. 2); wherein docking against homology modeled targets are possible for proteins whose structures are not known (pg. 91 Abstract); wherein the reviewed structure-based drug design is a powerful technique for the rapid identification of small molecules against homology models (pg. 98 col. 2 para. 3).
Claim 6 recites:
wherein the 3D structure of the wild-type or homolog protein of step (ii) is a crystal structure, a 3D NMR structure or a calculated hypothetical three-dimensional structure; and/or the mutation is a point mutation and the mutated protein differs from the non-mutated protein by a single amino acid moiety only and each docking space embraces the different single amino acid moiety
• Niu teaches annotated gene variants aligned and mapped onto appropriate wild type PDB (Protein Database) three-dimensional protein structures (pg.827 and Fig 1a); wherein PDB structures are primarily obtained through techniques like X-ray crystallography or NMR spectroscopy as evidenced by Berman (pg. 235 col. 1 para. 4).
Claim 7 recites:
a method of claim 2, wherein at least steps (ii)-(iv) are conducted using a software program.
• Niu teaches a computational tool HotSpot3D (i.e. software program) (pg. 827 col. 2 para. 3) that perform steps (ii) and (iii) as described in claim 2 above. Jordan teaches methods for large scale measurements of gene expression and mutation detection (pg. 251 Abstract) with application of algorithms for data acquis ion (i.e. software program) (pg. 253 col.2 para. 2) that perform step (i) as described in claim 2 above. Pagadala teaches computational tools for molecular docking methods (i.e. software program) that perform step (iv) as described in claim 2 above (pg. 92 col. 1 para. 2).
Claim 9 recites:
(v) determining the binding affinity of the compound to the docking space by:
(a) generating a 3D grid box of docking space of the mutated protein and of each compound, wherein each grid box comprises grid points defined in all three dimensions that provide pieces of information selected from the group consisting of charges, partial charges, the ability to form hydrogen bonds, the ability to form pi-pi-electron interactions, and the ability to form van-der-Waals forces;
(b) fitting each 3D structure of a compound with the one or more docking spaces in a manner that the 3D structure of the compound can rotate and scans over each docking space;
(c) determining the binding energy between each compound and each docking space at each grid point and calculating binding affinity for each compound at each 3D orientation with each docking space; and
(d) determining the lowest binding affinity for each compound-protein interaction; and
(vi) identifying one or more compounds specifically binding to the mutated protein
• Niu does not teach the recitation above. However, Pagadala teaches computational tools for molecular docking methods wherein docking algorithms predict the binding mode and binding affinity of a molecule to a binding pocket and also relative to other compounds (i.e. (v) determining the binding affinity of the compound to the docking space) (pg. 92 col. 1 para. 2); wherein docking algorithms generate docking conformations in a grid-based 3D space using an fast Fourier Transform (i.e. (a) generating a 3D grid box of docking space of the mutated protein and of each compound, wherein each grid box comprises grid points defined in all three dimensions) (pg. 93 col. 1 para. 2); performs a systematic rigid-body search of one molecule, carrying out both translational and rotational orientation on a second molecule (i.e. (b) fitting each 3D structure of a compound with the one or more docking spaces in a manner that the 3D structure of the compound can rotate and scans over each docking space) (pg. 93 col. 1 para. 2); scan using the translational and rotational space of two molecules based on surface complementarity and electrostatics (i.e. provide pieces of information consisting of charges and partial charges) (pg. 93 col. 1 para. 3); wherein proposed docking methods identify the known compounds with top scores in virtual screening trials (i.e. a top score in virtual screening reads on the most interactions with the target hence lowest binding affinity hence, (d) determining the lowest binding affinity for each compound-protein interaction) (pg. 92 col. 2 para. 3); wherein one method successfully designed inhibitors against proteases of schistosome and malaria pathogenicity by using shape-complementarity function and a simplified molecular-mechanics potential approximating the interaction energy between the protease and ligand (i.e. (vi) identifying one or more compounds specifically binding to the mutated protein) (pg. 94 col. 1 para. 3).
Claim 10 recites:
defining one or more docking spaces of the structure of the wild-type or homolog protein of step (ii) each corresponding to the respective docking spaces of the structure of the mutated protein of step (iii);
fitting the compounds with these one or more docking spaces;
determining the lowest binding energy of each compound to these one or more docking spaces and thereby
determining the binding affinity;
comparing the binding affinity of each compound to the docking spaces of the mutated and of the wild-type or homolog protein; and
identifying one or more compounds having a higher binding affinity to the docking space of the wild-type or homolog protein than to the corresponding docking space of the mutated protein
• Niu does not teach the recitation above. However, Pagadala teaches computational tools for molecular docking methods wherein one method successfully designed inhibitors against proteases of schistosome and malaria pathogenicity by using shape-complementarity function and a simplified molecular-mechanics potential approximating the interaction energy between the protease and ligand (i.e. (vi) identifying one or more compounds specifically binding to the mutated protein) (pg. 94 col. 1 para. 3); wherein flexible docking predict the binding mode and binding affinity relative to other compounds (i.e. fitting the compounds with these one or more docking spaces) (pg. 92 col. 1 para. 2) wherein rigid docking produces a large number of docked conformations with favorable surface complementarity, followed by the reranking of the conformations using the free energy of approximation to determine binding affinity (i.e. determining the lowest binding energy of each compound to these one or more docking spaces and thereby determining the binding affinity and comparing binding affinity to identify higher binding affinity) (pg. 92 col. 2 para. 3); wherein docking against homology modeled targets are possible for proteins whose structures are not known (pg. 91 Abstract); wherein the reviewed structure-based drug design is a powerful technique for the rapid identification of small molecules against homology models (i.e. defining one or more docking spaces of the structure of the wild-type or homolog protein of step (ii) each corresponding to the respective docking spaces of the structure) (pg. 98 col. 2 para. 3).
Rationale for combining (MPEP §2142-2143)
Regarding claims 2, 6-7 and 9-10, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine, in the course of routine experimentation and with a reasonable expectation of success, the methods of Niu and Pagadala in view of Jordan because all references disclose methods for investigation of gene expression products. The motivation would have been to interpret massive amount of data, correlate it with available information and extract as much biological significance as possible (pg. 258 col. 1 para. 2 Jordan). Therefore it would have been obvious to one of ordinary skill in the art to substitute the investigation of gene expression products of Niu and Pagadala to the methods by Jordan because such a substitution is no more than the simple substitution of one known element for another. One of ordinary skill in the art would be able to motivated to combine the teachings in these references with a reasonable expectation of success since the described teachings pertain to methods for investigation of gene expression products.
C. Claims 19-20 are rejected under 35 U.S.C. 103(a) as being unpatentable over Niu as evidenced by Tomczak in view of Pagadala as applied to claim 1 and in view of Jordan as applied to claim 2 above, further in view of Shim ("Recent advances in drug repositioning for the discovery of new anticancer drugs." Int. J. Biol. Sci. 10(7):654–663 (2014)), as cited on the 04/11/2025 Form PTO-892. Any newly recited portions are necessitated by claim amendment.
Claim 19 recites:
further comprises the step (vii) of determining toxicological and pharmacologic properties of the compounds identified in step (vi) from one or more databases and identifying a compound of comparably low toxicity and, high pharmacologic activity in antineoplastic treatment
Claim 20 recites:
wherein said method is a method for identifying an antineoplastic agent which has antineoplastic activity against the neoplasm, wherein said antineoplastic agent is or comprises one or more compounds identified in any of steps (vi) or (vii)
• Niu and Pagadala do not teach the recitation above. However, Shim teaches a method for the discovery of new anticancer drugs (pg. 654 para. 1); with focus on toxicity analysis (pg. 656 col. 2 para. 1) and pharmacology analysis (i.e. determining toxicological and pharmacologic properties of the compounds and identifying a compound of comparably low toxicity and, high pharmacologic activity in antineoplastic treatment as in claim 19) (pg. 661 Table 2). It is interpreted that the recited " for identifying an antineoplastic agent which has antineoplastic activity against the neoplasm" in claim 20 constitutes intended use and therefore not a required limitation.
Rationale for combining (MPEP §2142-2143)
Regarding claims 19-20, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine, in the course of routine experimentation and with a reasonable expectation of success, the methods of Niu, Pagadala, and Jordan in view of Shim because all references disclose methods for investigation of interactions between a compound and a target structure. The motivation would have been to quickly identify clinically advanced anticancer drugs against targets of interest (pg. 661 col. para. 1 Shim). Therefore it would have been obvious to one of ordinary skill in the art to substitute the investigation of interactions between a compound and a target structure of Niu and Pagadala to the methods by Shim because such a substitution is no more than the simple substitution of one known element for another. One of ordinary skill in the art would be able to motivated to combine the teachings in these references with a reasonable expectation of success since the described teachings pertain to methods for investigation of interactions between a compound and a target structure.
Response to applicant's remarks in regard to Claim Rejection 35 U.S.C. ~ 103
The Remarks of 04/10/2026 have been fully considered but are not persuasive for the reasons below:
It appears that pg. 11 para. 2 represents the only Applicant remarks specific to 103 and the instant claims (emphasis added):
Applicant respectfully disagrees. The inventive contribution of the claimed invention resides in the specific combination of using the docking space of non-wild-type protein, encoded by an mRNA transcript comprising at least one mutation obtained from at least one diseased cell of a diseased tissue or bodily fluid of an individual patient, and screening compounds that bind to a homology-modeled protein surface derived from the non-wild-type protein. A key distinction between the present invention and the disclosure of Niu lies in the focus of the respective approaches. As indicated, for example, in the Abstract, Niu investigates tissues from 19 cancer types broadly, rather than targeting a specifically identified diseased tissue. Moreover, Niu emphasizes the analysis of local concentrations of mutations, rather than focusing on one or more specific mutations within the transcriptome. The objective of Niu appears to be the identification of general mutation patterns and the development of broadly applicable cancer treatment compounds. In contrast, the present invention is directed toward identifying individualized treatment strategies tailored to a specific diseased tissue, which is an approach aligned with the principles of personalized medicine. Accordingly, it is not reasonable that a person skilled in the art would have considered Niu when attempting to solve the problem of providing novel, individualized therapeutic compounds solved by the claimed invention
It is respectfully submitted that this is not persuasive because the claimed "specific combination of using the docking space of non-wild-type protein, encoded by an mRNA transcript comprising at least one mutation obtained from at least one diseased cell of a diseased tissue or bodily fluid of an individual patient, and screening compounds that bind to a homology-modeled protein surface derived from the non-wild-type protein" is currently taught by the combination of references described in this examination. See Claim Rejections above. The cancer types investigated by Niu indeed read on the recited "diseased cell or tissue" under BRI; hence there is no distinction between the recited limitation and the described teachings. Regarding the argued "specific mutations within the transcriptome", the prior art to Niu discloses the proposed method using a comprehensive database for protein sequence and annotation data and to retrieve IDs from the PDB, transcript and protein IDs information (Online Methods – pg. 1 col. 1 para. 2); reading on the investigation of specific information regarding the mutation and related transcriptome information.
Similar arguments are stated for the instant dependent claims relying on the alleged deficiencies by Niu and Pagadala. There are no deficiencies in the teachings by Niu and Pagadala as described above.
Thus, it is reasonable that a person skilled in the art would have considered Niu and additional disclosed prior art references to arrive at the claimed invention because the prima facie case of obviousness has been established. MPEP 2141.III for "RATIONALES TO SUPPORT REJECTIONS UNDER 35 U.S.C. 103"; wherein "(G) Some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention." Furthermore, in this instant application, the amendments support existing claim rejections, in which the recited limitations are all addressed, see Claim Rejections above.
Conclusion
No claims are allowed.
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/F.F.L./Examiner, Art Unit 1685
/JANNA NICOLE SCHULTZHAUS/Examiner, Art Unit 1685
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