DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
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.
Election/Restrictions
Applicant’s election without traverse of Group II, encompassed by claims 3-6, in the reply filed on Sep 29 2025 is acknowledged.
As Applicant has cancelled all non-elected claims, the only pending claims are elected claims and no claims are withdrawn.
Claim Status
Claims 3-6 are pending.
Claims 1-2 and 7-15 are canceled.
Claim 3 is objected to.
Claims 3-6 are rejected.
Priority
The instant Application claims domestic benefit to US provisional application 63/287,228, filed Dec 8 2021. Accordingly, each of claims 3-6 are afforded the effective filing date of the Dec 8 2021.
Information Disclosure Statement
The information disclosure statements (IDS) filed on Jun 19 2025 and Dec 2 2025 are in compliance with the provisions of 37 CFR 1.97 and have therefore been considered. Signed copies of the IDS documents are included with this Office Action. FOR references 1 and 10 in IDS Jun 19 2025 have not been considered, as indicated by strikethrough on the IDS, because no English translation was provided.
Drawings
The drawings are objected to for the following informalities. In FIGURE 5, the various residues are shaded to show various features. At least the shading for “acidic” and “basic”, “polar” and “metal complex”, “greasy” and solvent residue”, and “solvent contact” and “metal/ion contact” residues or interactions are not distinguishable from one another.
Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Nucleotide and/or Amino Acid Sequence Disclosures
The sequence listing submitted Dec 7 2022 has been accepted.
Specification
The disclosure is objected to for the following informalities. It is noted that for purposes of the instant Office Action, any reference to the specification pertains to the specification as originally filed on Dec 7 2022.
Abstract
Applicant is reminded of the proper language and format for an abstract of the disclosure.
The abstract should be in narrative form and generally limited to a single paragraph on a separate sheet within the range of 50 to 150 words in length. The abstract should describe the disclosure sufficiently to assist readers in deciding whether there is a need for consulting the full patent text for details.
The language should be clear and concise and should not repeat information given in the title. It should avoid using phrases which can be implied, such as, “The disclosure concerns,” “The disclosure defined by this invention,” “The disclosure describes,” etc. In addition, the form and legal phraseology often used in patent claims, such as “means” and “said,” should be avoided.
The abstract is objected to because is less than 50 words in length and because it includes the phrase “space group space group” on line 1.
Disclosure
The formatting of the final sentence in [0029] is not correct because there appear to be missing “)” for the two “(“ included therein, as well as the sentence missing appropriate punctuation to make it two sentences.
Hyperlinks
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01. Non-limiting examples include paragraphs [0147]. Applicant will note that this is exemplary and other instances may exist. It is requested that all instances be corrected.
Trade Names
The use of the term BioWave at [0258], as an example, which are trade names or marks used in commerce, have been noted in this application. Each term should be accompanied by corresponding generic terminology; furthermore the terms should be capitalized wherever they appear or, where appropriate, include a proper symbol indicating use in commerce such as ™, ™, or ® following the terms. Applicant is requested to review the Specification and Drawings for all instances of trade names or marks used in commerce.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) is permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
Appropriate correction for all objections to the specification is required.
Claim Objections
The claims are objected to for the following informalities:
Claim 3 recites “BTK” in line 1, which should be amended to spell out the entirety of the name of the protein as it is the first recitation of this abbreviation.
Claim 3 should be amended to remove the “has” on line 6 in front of “unit cell parameters”.
In claim 3, the comma at the end of the 7th line should be changed to a semicolon.
Claim 3, 8th line, recites “three dimensional”, which should be amended to recite “three-dimensional” to maintain consistent claim formatting.
Claim 3 recites, in the final limitation, a plurality of steps, such as: “contacting…” and “measuring…”. As set forth in 37 CFR 1.75, where a claim sets forth a plurality of steps, each step of the claim should be separated by a line indentation (see MPEP 608.01(i)).
Claim Rejections - 35 USC § 112
35 U.S.C. 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 4-6 are rejected under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor regards as the invention.
Claim 4 recites “wherein the candidate inhibitor makes a direct covalent bond with Cys 481”. Claim 5 recites “wherein the candidate inhibitor makes a hydrogen bond with Lys 430”. Claim 6 recites “wherein the candidate inhibitor makes a hydrogen bond with Met 477”. However, claim 3 recites only a binding site of BTK of SEQ ID NO. 3, which has only 271 AA. Therefore, SEQ ID NO. 3 does not have a Cys 481 as in claim 4, a Lys 430 as in claim 5, or a Met 477 as in claim 6, and the metes and bounds of the claims are not clear. For compact examination, any art teaching a candidate inhibitor making a direct covalent bond with any Cys or a hydrogen bond with any Lys or Met in SEQ ID NO. 3 will be considered relevant. The rejections may be overcome by clarifying which Cys, Lys, and Met in SEQ ID NO. 3 are being referenced.
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 3-6 are rejected under 35 U.S.C. 101 because the claimed invention is directed to one or more judicial exceptions without significantly more.
MPEP 2106 organizes judicial exception analysis into Steps 1, 2A (Prongs One and Two) and 2B as follows 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.
Framework with which to Evaluate Subject Matter Eligibility:
Step 1: Are the claims directed to a process, machine, manufacture, or composition of matter;
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;
Step 2A, Prong Two: If the claims recite a judicial exception under Prong One, then is the judicial exception integrated into a practical application (Prong Two); and
Step 2B: If the claims do not integrate the judicial exception, do the claims provide an inventive concept.
Framework Analysis as Pertains to the Instant Claims:
Step 1
With respect to Step 1: yes, the claims are directed to a method, i.e., a process, machine, or manufacture within the above 101 categories [Step 1: YES; See MPEP § 2106.03].
Step 2A, Prong One
With respect to Step 2A, Prong One, the claims recite judicial exceptions in the form of abstract ideas. The MPEP at 2106.04(a)(2) further explains that abstract ideas are defined as:
mathematical concepts (mathematical formulas or equations, mathematical relationships and mathematical calculations);
certain methods of organizing human activity (fundamental economic practices or principles, managing personal behavior or relationships or interactions between people); and/or
mental processes (procedures for observing, evaluating, analyzing/ judging and organizing information).
The claims also recite a law of nature or a natural phenomenon. The MPEP at 2106.04(b) further explains that laws of nature and natural phenomena include naturally occurring principles/relations and nature-based products that are naturally occurring or that do not have markedly different characteristics compared to what occurs in nature.
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 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:
Independent claim 3: employing said three dimensional structure to design or select a candidate inhibitor.
Dependent claims 4-6 recite limitations that further limit the recited judicial exception in the claims. For example, claims 4-6 further limit the amino acids that the candidate inhibitor interacts with during the employing step of claim 3.
The abstract ideas recited in the claims are evaluated under the Broadest Reasonable Interpretation (BRI) and determined to each cover performance either in the mind because the method only requires a user to manually design or select an inhibitor. Without further detail as to the methodology involved in “employing”, “design”, or “select”, under the BRI, one may simply, for example, use pen and paper or a visual examination of the three-dimensional structure to design or select a molecule which would fit into space in the three-dimensional structure and be a candidate inhibitor.
The claims also recite a natural relationship between the three-dimensional structure of the SEQ ID NO. 3 portion of BTK and inhibitors which can interact with this structure. Therefore, the claims recite a law of nature or a natural phenomenon.
Therefore, claim 3 and those claims dependent therefrom recite an abstract idea and a law of nature/natural phenomenon [Step 2A, Prong 1: YES; See MPEP § 2106.04].
Step 2A, Prong Two
Because the claims do recite judicial exceptions, direction under Step 2A, Prong Two, provides that the claims must be examined further to determine whether they integrate the judicial exceptions into a practical application (MPEP 2106.04(d)). A claim can be said to integrate a judicial exception into a practical application when it applies, relies on, or uses the judicial exception in a manner that imposes a meaningful limit on the judicial exception. This is performed by analyzing the additional elements of the claim to determine if the judicial exceptions are integrated into a practical application (MPEP 2106.04(d).I.; MPEP 2106.05(a-h)). If the claim contains no additional elements beyond the judicial exceptions, the claim is said to fail to integrate the judicial exceptions into a practical application (MPEP 2106.04(d).III).
Additional elements, Step 2A, Prong Two
With respect to the instant recitations, the claims recite the following additional elements:
Independent claim 3: generating a three-dimensional structure of a binding site of BTK on a computer, wherein the three dimensional structure coordinates possess the unit cell and space group parameters of the crystalline composition of SEQ ID NO. 3, and a ligand, characterized with space group p 2 21 21 and has unit cell parameters a=38.155 ± 2A; b=72.394 ± 2A; and
contacting said candidate inhibitor with human BTK and measuring the ability of said candidate inhibitor to bind to BTK.
The claims also include non-abstract computing elements. For example, independent claim 3 includes a computer for generating the three-dimensional structure.
Considerations under Step 2A, Prong Two
With respect to Step 2A, Prong Two, the additional elements of the claims do not integrate the judicial exceptions into a practical application for the following reasons. Those steps directed to data gathering, such as “generating a three-dimensional structure”, perform functions of collecting the data needed to carry out the judicial exceptions. Data gathering and outputting do not impose any meaningful limitation on the judicial exceptions, or on how the judicial exceptions are performed. Data gathering and outputting steps are not sufficient to integrate judicial exceptions into a practical application (MPEP 2106.05(g)).
The steps directed to “contacting said candidate inhibitor with human BTK” and “measuring the ability of said candidate inhibitor to bind to BTK” recite mere instructions to apply the exception in a generic way. Further, the claims merely recite the idea of a solution or an outcome of contacting the candidate inhibitor with BTK to measure the binding ability without reciting details of how the solution to a problem is accomplished or used (MPEP 2105.05(f)).
Further steps directed to additional non-abstract elements of a 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, such as the computer-readable recording media, are used to implement these functions. The claims state nothing more than a generic computer which performs the functions that constitute the judicial exceptions. Hence, these are mere instructions to apply the judicial exceptions using a computer, and therefore the claim does not integrate that judicial exceptions into a practical application. The courts have weighed in and consistently maintained that when, for example, a memory, display, processor, machine, etc.… are recited so generically (i.e., no details are provided) that they represent no more than mere instructions to apply the judicial exception on a computer, and these limitations may be viewed as nothing more than generally linking the use of the judicial exception to the technological environment of a computer (MPEP 2106.05(f)).
The specification as published discloses that an understanding of the associations between the enzyme binding pocket and a ligand will help lead to the design of drugs having more favorable associations with their target receptor or enzyme, and thus, improved biological effects at [0139], but does not provide a clear explanation for how the additional elements provide these improvements. Therefore, the additional elements do not clearly improve the functioning of a computer, or comprise an improvement to any other technical field. Further, the additional elements do not clearly affect a particular treatment; they do not clearly require or set forth a particular machine; they do not clearly effect a transformation of matter; nor do they clearly provide a nonconventional or unconventional step (MPEP2106.04(d)).
Thus, none of the claims recite additional elements which would integrate a judicial exception into a practical application, and the claims are directed to one or more judicial exceptions [Step 2A, Prong 2: NO; See MPEP § 2106.04(d)].
Step 2B (MPEP 2106.05.A i-vi)
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 prosecution 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).
With respect to the instant claims, the prior art review to Ghosh (Current Opinion in Chemical Biology, 2006, 10(3):194-202; newly cited) discloses that generating a three-dimensional structure of a molecule, contacting molecules and candidate inhibitors, and measuring binding ability are additional elements that are routine, well-understood and conventional in the art. Said portions of the prior art are, for example, the abstract and Figure 1, although the entire document is relevant. Further, the specification as published discloses that commercially or publicly available software is capable of generating a three-dimensional structure or a three-dimensional representation of molecules or portions thereof from a set of structure coordinates [0166; 0174; 0179; 0189; 0215]. As such, the claims simply append well-understood, routine, conventional activities previously known to the industry, specified at a high level of generality, to the judicial exception (MPEP2106.05(d)). The data gathering steps as recited in the instant claims constitute a general link to a technological environment which is insufficient to constitute an inventive concept which would render the claims significantly more than the judicial exception (MPEP2106.05(g)&(h)).
With respect to claims 3 and those claims dependent therefrom, the computer-related elements or the general purpose computer do not rise to the level of significantly more than the judicial exception. The claims state nothing more than a generic computer which performs the functions that constitute the judicial exceptions. Hence, these are mere instructions to apply the judicial exceptions using a computer, which the courts have found to not provide significantly more when recited in a claim with a judicial exception (Alice Corp., 573 U.S. at 225-26, 110 USPQ2d at 1984; see MPEP 2106.05(A)). The specification as published also notes that computer processors and systems, as example, are commercially available or widely used at [0168-0172]. The additional elements are set forth at such a high level of generality that they can be met by a general purpose computer. Therefore, the computer components constitute no more than a general link to a technological environment, which is insufficient to constitute an inventive concept that would render the claims significantly more than the judicial exceptions (see MPEP 2106.05(b)I-III).
Taken alone, the additional elements do not amount to significantly more than the above-identified judicial exception(s). Even when viewed as a combination, the additional elements fail to transform the exception into a patent-eligible application of that exception. Thus, the claims as a whole do not amount to significantly more than the exception itself [Step 2B: NO; See MPEP § 2106.05].
Therefore, the instant claims are not drawn to eligible subject matter as they are directed to one or more judicial exceptions without significantly more. For additional guidance, applicant is directed generally to the MPEP § 2106.
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 3-6 are rejected under 35 U.S.C. 103 as being unpatentable over Uckun (US20050196851; newly cited), as evidenced by Uckun et al. (Science, 1996, 273(5278):1096-1100; newly cited), in view of Marcotte et al. (Protein Science, 2010, 19(3):429-439; newly cited) as evidenced by 3GEN (rcsb.org/fasta/entry/3GEN/display).
The prior art to Uckun discloses crystal structure of the kinase domain of BTK, as well as use of the crystal structure in the design, identification, and verification of ligands that modulate BTK activity (abstract). Uckun, indicated by the open circles, teaches the instant features, indicated by the closed circles, as follows. Instantly claimed elements which are considered to be equivalent to the prior art teachings are described in bold for all claims.
Claim 1 discloses a method for identifying and/or designing a candidate inhibitor of BTK, wherein said method comprises:
generating a three-dimensional structure of a binding site of BTK on a computer, wherein the three dimensional structure coordinates possess the unit cell and space group parameters of the crystalline composition of SEQ ID NO. 3, and a ligand, characterized with space group p 2 21 21 and has unit cell parameters a=38.155 ± 2A; b=72.394 ± 2A;c=103.946± 2A; a=90°; b=90°; g=90°, employing said three dimensional structure to design or select a candidate inhibitor; and
Uckun teaches determining the X-ray crystal structure of the murine kinase domain of BTK (BTK-KD), which is from residues I397-S659 of the full length murine BTK [0011; 0025; 0183-0192]. Uckun teaches that in human BTK, the kinase domain is approximately 256 aa long and span residues K400-E658, and that murine BTK-KD is 99% conserved [0090-0091]. Uckun teaches that the crystal structure of the murine BTK-KD has a space group P212121 and each cell unit has the approximate dimensions of a=45±5 Å, b=104±10 Å, c=116±10 Å, α=β=γ=90° [0098].
Uckun teaches modeling the interaction of ligands with BTK-KD and the rational design of modulators of BTK activity by generating, using a computer, a graphical three-dimensional representation of at least one molecule or molecular complex comprising at least a portion of a BTK kinase domain binding pocket with the dimensions discovered in the crystal structure, and then using the three-dimensional model to identify inhibitors and stimulators of BTK activity (i.e., generating and employing a three-dimensional structure to design or select a candidate inhibitor) ([0011; 0118-0129; 0165-0177; 0223-0224]; claims 8-9 and 11-14; Table 1).
See below for teachings by Marcotte regarding SEQ ID NO. 3 and the unit cell parameters.
contacting said candidate inhibitor with human BTK and measuring the ability of said candidate inhibitor to bind to BTK.
Uckun teaches activation and inhibition of BTK by screening agents identified as candidate molecules for modulating the activity of BTK using known bioassays, such as inhibiting the anti-apoptotic effects of BTK (i.e., contacting said candidate inhibitor with BTK and measuring the ability of said candidate inhibitor to bind to BTK) [0011; 0156; 0225-0226]. Uckun teaches uses DT-40 cells in the apoptosis assay according to the previously described methods of Uckun 1996 [0225; 0293], which describes the process of determining the effects of the human BTK to restore the apoptotic response in DT-40 lymphoma B cells (abstract; p. 1097, col. 1, last paragraph; p. 1099; col. 1, last paragraph). Therefore, Uckun as evidenced by Uckun 1996 teaches contacting candidate inhibitors with human BTK as instantly claimed.
Uckun does not teach the crystalline composition of SEQ ID NO. 3, and a ligand, characterized with space group p 2 21 21 and has unit cell parameters a=38.155 ± 2A; b=72.394 ± 2A;c=103.946± 2A.
However, the prior art to Marcotte discloses the crystal structures of the human BTK kinase domain bound to two separate molecules which inhibit BTK, Dasatinub and B43 (abstract; p. 430, col. 1, par. 2 through col. 2, par. 1). Marcotte teaches cloning, expressing, and purifying the kinase domain of human BTK with residues 382-659 (p. 437, col. 1, par. 2) followed by crystallization for structure determination when bound to Dasatinub or B43 (p. 437, col. 2, par. 5 through p. 438, col. 1, par. 2). Marcotte teaches that depositing information regarding the protein sequence and the complex structures at rcsb.org, where the protein sequence for BTK-KD can be found under the PDB ID: 3K54. Sequence alignment between SEQ ID NO. 3 and the BTK-KD of 3GEN examined by Marcotte is 100%, as shown below, where Qy is SEQ ID NO. 3. Therefore, as evidenced by 3GEN, Marcotte teaches the crystalline composition of SEQ ID NO. 3.
PNG
media_image1.png
426
634
media_image1.png
Greyscale
Marcotte teaches that the BTK-KD/B43 complex has space group P21212 and cell dimensions of a=72.5, b=104.3, and c=38.0, and that the BTK-KD Y551E/Dasatinub complex has space group P21212 and cell dimensions of a=72.5, b=104.3, and c=38.0 (Table 1). Both complexes of Marcotte are therefore considered to anticipate the instantly claimed unit cell parameters a=38.155 ± 2A; b=72.394 ± 2A;c=103.946± 2A.
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, Uckun and Marcotte because both references disclose methods for examining the crystal structure of BTK-KD. The motivation to substitute human BTK-KD examined by Marcotte for murine BTK-KD examined by Uckun would have been to examine more relevant structures for drug discovery as the human BTK-KD structural complexes differ from those reported in the past for murine BTK-KD, as taught by Marcotte (p. 433, col. 1, par. 2 through col. 2, par. 1). Therefore, it would have been obvious to one of ordinary skill in the art to substitute human BTK-KD for murine BTK-KD for the predictable result of predicting more relevant inhibitors of human BTK.
Regarding claims 4-6, Uckun, as evidenced by Uckun 1996, in view of Marcotte, as evidenced by 3GEN, teaches the method of claim 3 as described above. Claims 4-6 further add that the candidate inhibitor makes a direct covalent bond with Cys 481 (claim 4) or a hydrogen bond with Lys 430 (claim 5) or Met 477 (claim 6).
As discussed in the above 35 USC 112(b) rejection, SEQ ID NO. 3 does not contain these specific residues. However, in the interest of compact examination, it is noted that Marcotte teaches examining Cys481 (p. 435, col. 2, par. 1) or C 481, K 430 (i.e., Lys 430), and M 477 (i.e., Met 477) because these residues are within 5A of compounds in the BTK-KD complex structures (Table III). Marcotte teaches that Cys481 is a target because a small molecule may irreversibly bind to this cysteine via a covalent bond p. 435, col. 2, par. 1). Marcotte also teaches a hydrogen bond interaction at residue Met477 (p. 432, col. 1, par. 5l p. 433, col. 1, par. 1). Further, Uckun teaches hydrogen bonding to K430 [0105; 0112; 0210-0212], which Uckun teaches in an invariant residue in the structural super family of protein kinases [0210].
Regarding claims 4-6, 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 examine the specific bond interactions at the recited residues when identifying candidate inhibitors because those residues are known in the prior art to be involved with the binding pocket of BTK-KD, as taught by both Uckun [0121] and Marcotte (at least Table III).
Conclusion
No claims are allowed.
Inquiries
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JANNA NICOLE SCHULTZHAUS whose telephone number is (571)272-0812. The examiner can normally be reached on Monday - Friday 8-4.
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/JANNA NICOLE SCHULTZHAUS/Examiner, Art Unit 1685