DETAILED ACTION
Election/Restrictions
Applicant’s election with traverse of Group I, claims 1, 5, 8, 11, 12, 19, 25-29, 56, 57, 59, and 63-65 and without traverse of species (1) (the nuclease is a restriction endonuclease, see claims 56, 57, and 59), a species that the non-ligatable end lacks a 3’ hydroxyl group in claim 26, a species that the ligated probe is a circular probe in claim 28, and a species of the restriction endonuclease which generates sticky ends in claim 59 in the reply filed on November 26, 2025 is acknowledged. The traversal is on the ground(s) that “[A]pplicant respectfully traverses this rejection with respect to Group I and Group II because the two groups are not ‘independent or distinct’ as claimed. See MPEP § 803 (‘There are two criteria for a proper restriction requirement for restriction between patentably distinct inventions: (A) the inventions must be independent (see MPEP § 802.01, § 806.06, § 808.01) or distinct as claimed (see MPEP § 806.05 - § 806.05(j)),’ emphasis added). As an initial matter, the Examiner has not clearly stated which claimed subject matter falls within the scope of Group I and which claimed subject matter falls within the scope of Group II. There Examiner states that both Group I and Group II are ‘drawn to a method for analyzing a target nucleic acid’ and fall within the same classification (C12Q 1/68). Page 2 of the October 2, 2025, Office Action. However, the Examiner concludes that ‘Groups 1 and Il are distinct inventions which are directed to two different methods which have different properties,’ and alleges an example that "the search required for Group I such as contacting the target nucleic acid with one probe in step a) of claim 1 is not required for Group II while the search required for Group II such as contacting the target nucleic acid with a probe set in step a) of claim 1 is not required for Group II.’ Page 2 of the October 2, 2025, Office Action. Applicant submits that the restriction requirement between Group I and Group II is improper because the claimed subject matter does not meet the criteria for independence or distinctness. See MPEP § 802.01 (‘The term ‘independent’ (i.e., unrelated) means that there is no disclosed relationship between the two or more inventions claimed, that is, they are unconnected in design, operation, and effect.’) As stated in paragraph [0061] of the application, ‘a probe (e.g., a circularizable probe, or one of a first and second probe in a probe set),’ a person having ordinary skill in the art would recognize the terms ‘a probe’ and ‘probe set’ as connected in design, operation, and effect as they both hybridize to the target nucleic acid as claimed. Furthermore, claim 1 does not recite the term ‘one probe,’ as stated by the Examiner, but instead uses the term ‘a probe.’ As stated in paragraph [0357] of the application, ‘As used herein, the singular forms ‘a,’ ‘an,’ and ‘the’ comprise plural referents unless the context clearly dictates otherwise. For example, ‘a’ or ‘an’ means ‘at least one’ or ‘one or more’’. Thus, recitation of ‘a probe’ in claim 1 should be read to encompass ‘at least one probe’ or ‘one or more probes.’ A person having ordinary skill in the art reading the disclosure of the application would not deem the term probe and probe set to be distinct from one another. Thus, the scope of Group II is fully encompassed within the scope of Group I, as the subject matter is claimed, and cannot be considered ‘independent or distinct’ as required for a proper restriction requirement. An election of an invention that includes search an examination of a ‘method for analyzing a target nucleic acid, comprising: a) contacting the target nucleic acid with a probe,’ presumably as the Examiner intended to fall within the scope of Group I, necessarily requires search and examination of a ‘method for analyzing a target nucleic acid, comprising: a) probe set,’ presumably as the Examiner intended to contacting the target nucleic acid with a fall within the scope of Group II. The Examiner's assertion that ‘different and distinct searches will have to be performed’ is unsupported and conclusory. Page 2 of the October 2, 2025, Office Action. As stated in the MPEP, ‘where, however, the classification is the same and the field of search is the same and there is no clear indication of separate future classification and field of search, no reasons exist for dividing among independent or related inventions.’ (MPEP § 808.02). Thus, there is no serious search and/or examination burden on the examiner if restriction is not required. The Examiner has not articulated any particular reasons and merely asserts that the methods have ‘different properties’ without articulating what those properties are and why they are independent or distinct. Page 2 of the October 2, 2025, Office Action. See MPEP § 808.01 (‘The particular reasons relied on by the examiner for holding that the inventions as claimed are either independent or distinct should be concisely stated. A mere statement of conclusion is inadequate. The reasons upon which the conclusion is based should be given.’). Accordingly, for at least the reason discussed above, Applicant respectfully traverses the restriction requirement and request that the subject matter of both Group I and Group II, as set forth by the Examiner, be searched and examined in the present application”.
The above arguments have been fully considered and have not been found persuasive toward the withdrawal of the restriction requirement nor persuasive toward the relaxation of same such that Groups I and II will be examined. Although applicant argues that “[A]s stated in paragraph [0357] of the application, ‘As used herein, the singular forms ‘a,’ ‘an,’ and ‘the’ comprise plural referents unless the context clearly dictates otherwise. For example, ‘a’ or ‘an’ means ‘at least one’ or ‘one or more’’. Thus, recitation of ‘a probe’ in claim 1 should be read to encompass ‘at least one probe’ or ‘one or more probes.’ Thus, recitation of ‘a probe’ in claim 1 should be read to encompass ‘at least one probe’ or ‘one or more probes.’ A person having ordinary skill in the art reading the disclosure of the application would not deem the term probe and probe set to be distinct from one another. Thus, the scope of Group II is fully encompassed within the scope of Group I, as the subject matter is claimed, and cannot be considered ‘independent or distinct’ as required for a proper restriction requirement”, since the phrase “a probe set” in claim 1 means two or more probes and paragraph [0061] of this instant application states “a probe (e.g., a circularizable probe, or one of a first and second probe in a probe set)”,
the phrase “a probe” in claim 1 must have a different meaning from the phrase “a probe set” and can be reasonably read as one probe. Furthermore, since page 2 of the restriction requirement mailed on October 2, 2025 clearly stated that “[G]roups I and II are distinct and independent inventions which are directed to two different methods which have different properties. As a result, different and distinct searches will have to be performed. For example, the search required for Group I such as contacting the target nucleic acid with one probe in step a) of claim 1 is not required for Group II while the search required for Group II such as contacting the target nucleic acid with a probe set in step a) of claim 1 is not required for Group II”, Groups I and II are distinct and independent inventions and applicant appears to put two distinct and independent inventions to a single independent claim. Although applicant argues that “[A]s stated in the MPEP, ‘where, however, the classification is the same and the field of search is the same and there is no clear indication of separate future classification and field of search, no reasons exist for dividing among independent or related inventions.’ (MPEP § 808.02). Thus, there is no serious search and/or examination burden on the examiner if restriction is not required”, the restriction requirement is not dependent on the classification of Groups I and II as argued by applicant and is based on that the searches for Groups I and II is not overlap and there is a burden for the examiner to search Groups I and II together. In addition, applicant has no evidence to show that “there is no serious search and/or examination burden on the examiner if restriction is not required” as argued by applicant. Therefore, the requirement is still deemed proper and is made FINAL. However, if applicant amended the phrase “a probe” in claim 1 to “two or more probes”, the examiner may agree to consider rejoining claim 15 with Group I. Claims 1, 5, 8, 11, 12, 19, 25, 26, 28, 29, 56, and 59 will be examined.
Information Disclosure Statement
The information disclosure statements filed on June 26, 2023 and November 26, 2025 contain 23 pages and 436 patent and non-patent literatures. However, most of these patent and non-patent literatures are unrelated to this instant application. Applicant may only consider to file patent and non-patent literatures related to this instant applicant in the information disclosure statements such that a valuable time of the examiner will not be wasted .
Claim Objections
Claim 19 is objected to because of the following informality: “the cleaving” should be “the cleaving step”.
Claim 25 is objected to because of the following informality: “the cleaving in b)” should be “the cleaving step”.
Claim 59 is objected to because of the following informality: “cleavage by the restriction endonuclease generates sticky ends” should be “the restriction endonuclease is a restriction endonuclease which generates sticky ends”.
Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Scope of Enablement
Claims 1, 5, 8, 11, 12, 19, 25, 26, 28, 29, 56, and 59 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for
analyzing a target nucleic acid using the methods recited in claims 1, 5, 8, 11, 12, 19, 25, 26, 28, 29, 56, and 59 when the probe comprises: i) a first hybridization region capable of hybridizing to a first target sequence in the target nucleic acid, ii) a second hybridization region capable of hybridizing to a second target sequence in the target nucleic acid, and iii) a duplex region comprising an interrogatory region, wherein upon hybridization of the probe to the target nucleic acid, the duplex region is positioned between the first hybridization region and the second hybridization regions and the interrogatory region hybridizes to a region of the target nucleic acid after cleaving the probe in a complex formed by the target nucleic acid and the probe and releasing a portion of the duplex region from the complex formed by the target nucleic acid and the probe, does not reasonably provide enablement for analyzing a target nucleic acid using the methods recited in claims 1, 5, 8, 11, 12, 19, 25, 26, 28, 29, 56, and 59 when the probe comprises: i) a first hybridization region capable of hybridizing to a first target sequence in the target nucleic acid, ii) a second hybridization region capable of hybridizing to a second target sequence in the target nucleic acid, and iii) a duplex region comprising an interrogatory region, wherein upon hybridization of the probe to the target nucleic acid, the duplex region is positioned between the first hybridization region and the second hybridization regions and the interrogatory region does not hybridize to a region of the target nucleic acid after cleaving the probe in a complex formed by the target nucleic acid and the probe and releasing a portion of the duplex region from the complex formed by the target nucleic acid and the probe. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
Factors to be considered in determining whether a disclosure meets the enablement requirement of 35 USC 112, first paragraph, have been described by the court in In re Wands, 8 USPQ2d 1400 (CA FC 1988). Wands states at page 1404,
“Factors to be considered in determining whether a disclosure would require undue experimentation have been summarized by the board in Ex parte Forman. They include (1) the quantity of experimentation necessary, (2) the amount of direction or guidance presented, (3) the presence or absence of working examples, (4) the nature of the invention, (5) the state of the prior art, (6) the relative skill of those in the art, (7) the predictability or unpredictability of the art, and (8) the breadth of the claims.”
The Nature of The Invention
The claims are drawn to a method for analyzing a target nucleic acid. The invention is a class of invention which the CAFC has characterized as “the unpredictable arts such as chemistry and biology.” Mycogen Plant Sci., Inc. v. Monsanto Co., 243 F.3d 1316, 1330 (Fed. Cir. 2001).
The Breadth of The Claims
Claims 1, 5, 8, 11, 12, 19, 25, 26, 28, 29, 56, and 59 encompass a method for analyzing a target nucleic acid, comprising: a) contacting the target nucleic acid with a probe comprising: i) a first hybridization region capable of hybridizing to a first target sequence in the target nucleic acid, ii) a second hybridization region capable of hybridizing to a second target sequence in the target nucleic acid, and iii) a duplex region, wherein upon hybridization of the probe to the target nucleic acid, the duplex region is positioned between the first and second hybridization regions; b) cleaving the probe with a nuclease to generate a first ligatable end and release the duplex region or a portion thereof; c) ligating the first ligatable end to a second ligatable end in the probe hybridized to the target nucleic acid to generate a ligated probe; and d) detecting the ligated probe or a product thereof.
Working Examples
The specification provides 3 working examples (see pages 48 and 49 of US 2023/
0323430 A1, which is US publication of this instant case). However, the specification does not provide an example for analyzing a target nucleic acid using the methods recited in claims 1, 5, 8, 11, 12, 19, 25, 26, 28, 29, 56, and 59 when the probe comprises: i) a first hybridization region capable of hybridizing to a first target sequence in the target nucleic acid, ii) a second hybridization region capable of hybridizing to a second target sequence in the target nucleic acid, and iii) a duplex region comprising an interrogatory region, wherein upon hybridization of the probe to the target nucleic acid, the duplex region is positioned between the first hybridization region and the second hybridization regions and the interrogatory region does not hybridize to a region of the target nucleic acid after cleaving the probe in a complex formed by the target nucleic acid and the probe and releasing a portion of the duplex region from the complex formed by the target nucleic acid and the probe.
The Amount of Direction or Guidance Provided and The State of The Prior Art
Although the specification provides 3 working examples (see pages 48 and 49 of US 2023/0323430 A1, which is US publication of this instant case), the specification does not provide an example for analyzing a target nucleic acid using the methods recited in claims 1, 5, 8, 11, 12, 19, 25, 26, 28, 29, 56, and 59 when the probe comprises: i) a first hybridization region capable of hybridizing to a first target sequence in the target nucleic acid, ii) a second hybridization region capable of hybridizing to a second target sequence in the target nucleic acid, and iii) a duplex region comprising an interrogatory region, wherein upon hybridization of the probe to the target nucleic acid, the duplex region is positioned between the first hybridization region and the second hybridization regions and the interrogatory region does not hybridize to a region of the target nucleic acid after cleaving the probe in a complex formed by the target nucleic acid and the probe and releasing a portion of the duplex region from the complex formed by the target nucleic acid and the probe. Furthermore, there is no experimental condition and/or experimental data in the specification to support the claimed invention. During the process of the prior art search, the examiner has not found any prior art which is related to analyze a target nucleic acid using the methods recited in claims 1, 5, 8, 11, 12, 19, 25, 26, 28, 29, 56, and 59 when the probe comprises: i) a first hybridization region capable of hybridizing to a first target sequence in the target nucleic acid, ii) a second hybridization region capable of hybridizing to a second target sequence in the target nucleic acid, and iii) a duplex region comprising an interrogatory region, wherein upon hybridization of the probe to the target nucleic acid, the duplex region is positioned between the first hybridization region and the second hybridization regions and the interrogatory region does not hybridize to a region of the target nucleic acid after cleaving the probe in a complex formed by the target nucleic acid and the probe and releasing a portion of the duplex region from the complex formed by the target nucleic acid and the probe.
Level of Skill in The Art, The Unpredictability of The Art, and The Quantity of Experimentation Necessary
While the relative skill in the art is very high (the Ph.D. degree with laboratory experience), there is no predictability whether a target nucleic acid can be analyzed using the methods recited in claims 1, 5, 8, 11, 12, 19, 25, 26, 28, 29, 56, and 59 when the probe comprises: i) a first hybridization region capable of hybridizing to a first target sequence in the target nucleic acid, ii) a second hybridization region capable of hybridizing to a second target sequence in the target nucleic acid, and iii) a duplex region comprising an interrogatory region, wherein upon hybridization of the probe to the target nucleic acid, the duplex region is positioned between the first hybridization region and the second hybridization regions and the interrogatory region does not hybridize to a region of the target nucleic acid after cleaving the probe in a complex formed by the target nucleic acid and the probe and releasing a portion of the duplex region from the complex formed by the target nucleic acid and the probe.
Since the specification teaches that “[I]n some embodiments, e.g., as shown in FIG. 3, provided herein are methods for analyzing a biological sample comprising a plurality of target molecules (e.g., RNA) comprising a single nucleotide of interest, the methods comprising: a) contacting the biological sample with a circularizable probe comprising: i) a first hybridization region capable of hybridizing to a first target sequence in a target nucleic acid in the biological sample, ii) a second hybridization region capable of hybridizing to a second target sequence in the target nucleic acid, iii) a stem-loop structure at the 3’ or 5’ end of the circularizable probe, wherein the target nucleic acid comprises a region of interest and the stem-loop structure comprises an interrogatory region, and wherein upon hybridization of the circularizable probe to the target nucleic acid, the stem-loop structure is positioned between the first and second hybridization regions; b) cleaving the circularizable probe with a nuclease to generate a ligatable 3’ end or ligatable 5’ end and releasing the stem-loop structure or a portion thereof, thereby allowing the interrogatory region to hybridize to the region of interest; c) if the interrogatory region is complementary to the region of interest, ligating the ligatable 3’ end or ligatable 5’ end to the 5’ end or the 3’ end of the circularizable probe, respectively, to generate a circular probe using the target nucleic acid as template; and d) amplifying the circular probe using rolling circle amplification (RCA) to generate an RCA product; and e) detecting the RCA product in the biological sample”, “[F]IG. 3 depicts an exemplary probe comprising a stem-loop structure. The probe is contacted with a biological sample comprising a target nucleic acid (for example, RNA) comprising a region of interest such as a single nucleotide polymorphism (SNP) of interest. The probe can comprise a 5’ phosphate group and a stem-loop structure on its 3’ end. The hybridization region comprises an interrogatory region (for example, an interrogatory nucleotide) that is complementary to the region of interest (for example, correct SNP present, left side of FIG. 3). Alternatively, the probe may comprise an interrogatory region (for example, an interrogatory nucleotide) that is not complementary to the region of interest (for example, incorrect SNP present, right side of FIG. 3). The probe is processed by a nuclease to release the stem-loop structure and generate ligatable ends. If the target nucleic acid comprises the SNP of interest such that it is complementary to the interrogatory nucleotide, hybridization is stable and the 3’ and 5’ ends can be ligated to each other (left side of FIG. 3). However, if the target nucleic acid does not comprise a SNP complementary to the interrogatory nucleotide, hybridization is unstable, and the 3′ and 5′ ends are not ligated (right side of FIG. 3). In some embodiments, the interrogatory region can comprise one or more nucleotides that are part of the recognition sequence of the nuclease. In some embodiments, the stem-loop structure can be cleaved regardless of the identity of the interrogatory nucleotide. For example, cleavage of the duplex region can be constant across all probes or probe sets, regardless of the identity of the interrogatory region. In some embodiments, a probe comprising a stem-loop structure comprising a probe comprising an interrogatory region that is not complementary to the region of interest can be cleaved (e.g., as shown in the example of FIG. 3, right panel, depicting a incorrect SNP present in the target nucleic acid), but unstable hybridization between the interrogatory region and the region of interest (e.g., the single nucleotide of interest) will prevent subsequent ligation. Although FIG. 3 depicts a circularizable probe, it will be understood that an interrogatory region in a linear probe or probe set could similarly discriminate between different sequences of a region of interest, generating a ligated linear probe only in the presence of the correct sequence of the region of interest (e.g., the correct SNP)”, “[I]n the example shown in FIG. 3, the probe is a modified padlock probe for detecting an SNP, comprising a duplex region (such as a stem-loop structure) at the 3’ or 5’ end of the padlock probe. Such an approach can be used to increase specificity and stringency when detecting a region of interest (such as an SNP) in a target nucleic acid, such as an mRNA. The padlock probe comprises at least two hybridization regions that hybridize to complementary sequences on the target mRNA. The padlock probe comprises an interrogatory region complementary to the region of interest, at the 3’ or 5’ end of the probe. The interrogatory region connects the 3’ or 5’ end of the padlock probe to the stem-loop structure in such a manner that upon cleavage and release of the stem-loop structure, and generation of a ligatable end, the interrogatory region is free to hybridize to the region of interest in the target mRNA”, and “[A] mixture of probes is incubated with hybridization buffer for hybridization of the probes to target nucleic acid (such as mRNA) in the sample. The sample is washed and incubated with a nuclease (such as a restriction endonuclease, uracil-specific excision reagent enzyme, or a nickase) for cleavage of the stem-loop structure. The released stem-loop structure is then removed using a wash buffer. The buffer conditions used allow the probe to remain hybridized to the target nucleic acid. As shown in FIG. 3, if the complementary SNP is not present, the padlock probe would still bind the mRNA target to the complementary regions. However, the mismatched end, for example the 3’ end, will not hybridize to the region of interest in the mRNA and the ligation will be halted. Because the arm of the padlock probe is not fully hybridized, the padlock would be removed in a stringency wash. If the interrogatory region is complementary to the region of interest in the target mRNA, such that the padlock probe will be stably hybridized to the target, ligation will proceed. The sample is then incubated at room temperature with a T4 DNA ligase for ligation of the ligatable 3’ and 5’ ends of the padlock probes to form circularized probes. A primer for amplification of the circularized probe may be added. The sample is then incubated with a rolling-circle amplification (RCA) mixture containing a Phi29 DNA polymerase and dNTP for RCA of the circular probes. Fluorescently labeled oligonucleotides complementary to a portion of the RCA product, a barcode contained therein, or a secondary probe attached thereto are incubated with the sample. Multiple cycles of contacting the sample with probes and sequence determination (e.g., using in situ sequencing based on sequencing-by-ligation or sequencing-by-hybridization) can be performed. Fluorescent images can be obtained in each cycle, and one or more wash steps can be performed in a cycle or between cycles. Probe targeting various SNPs within or across genes can be sequentially or simultaneously provided, processed, and detected as described above” (see paragraphs [0080], [0200], [0377], and [0378], and Figure 3 of US 2023/0323430 A1, which is US publication of this instant case), the specification clearly indicate that a target nucleic acid cannot be analyzed when a probe comprises: i) a first hybridization region capable of hybridizing to a first target sequence in the target nucleic acid, ii) a second hybridization region capable of hybridizing to a second target sequence in the target nucleic acid, and iii) a duplex region comprising an interrogatory region, wherein upon hybridization of the probe to the target nucleic acid, the duplex region is positioned between the first hybridization region and the second hybridization regions and the interrogatory region does not hybridize to a region of the target nucleic acid after cleaving the probe in a complex formed by the target nucleic acid and the probe and releasing a portion of the duplex region from the complex formed by the target nucleic acid and the probe. Since claim 1 does not require that the duplex region comprises an interrogatory region and the interrogatory region hybridizes to a region of the target nucleic acid after cleaving the probe in a complex formed by the target nucleic acid and the probe and releasing a portion of the duplex region from the complex formed by the target nucleic acid and the probe, if the interrogatory region does not hybridize to a region of the target nucleic acid after cleaving the probe in a complex formed by the target nucleic acid and the probe and releasing a portion of the duplex region from the complex formed by the target nucleic acid and the probe, after step b) of claim 1, on a complex formed by the target nucleic acid and the cleaved probe,
the first end of the cleaved probe cannot be ligated to the second end of the cleaved probe such that a ligated probe cannot be generated in step c) of claim 1 and it is unpredictable how the ligated probe can be detected using the methods recited in claims 1, 5, 8, 11, 12, 19, 25, 26, 28, 29, 56, and 59.
Case law has established that “(t)o be enabling, the specification of a patent must teach those skilled in the art how to make and use the full scope of the claimed invention without ‘undue experimentation’.” In re Wright 990 F.2d 1557, 1561. In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970) it was determined that “[T]he scope of the claims must bear a reasonable correlation to the scope of enablement provided by the specification to persons of ordinary skill in the art”. The amount of guidance needed to enable the invention is related to the amount of knowledge in the art as well as the predictability in the art. Furthermore, the Court in Genentech Inc. v Novo Nordisk 42 USPQ2d 1001 held that “[I]t is the specification, not the knowledge of one skilled in the art that must supply the novel aspects of the invention in order to constitute adequate enablement”.
In view of above discussions, the skilled artisan will have no way to predict the experimental results. Accordingly, it is concluded that undue experimentation is required to make the invention as it is claimed. These undue experimentation at least includes to test whether a target nucleic acid can be analyzed using the methods recited in claims 1, 5, 8, 11, 12, 19, 25, 26, 28, 29, 56, and 59 when the probe comprises: i) a first hybridization region capable of hybridizing to a first target sequence in the target nucleic acid, ii) a second hybridization region capable of hybridizing to a second target sequence in the target nucleic acid, and iii) a duplex region comprising an interrogatory region, wherein upon hybridization of the probe to the target nucleic acid, the duplex region is positioned between the first hybridization region and the second hybridization regions and the interrogatory region does not hybridize to a region of the target nucleic acid after cleaving the probe in a complex formed by the target nucleic acid and the probe and releasing a portion of the duplex region from the complex formed by the target nucleic acid and the probe.
Conclusion
In the instant case, as discussed above, the level of unpredictability in the art is high, the specification provides one with no guidance that leads one to claimed methods. One of skill in the art cannot readily anticipate the effect of a change within the subject matter to which the claimed invention pertains. Thus given the broad claims in an art whose nature is identified as unpredictable, the unpredictability of that art, the large quantity of research required to define these unpredictable variables, the lack of guidance provided in the specification, the absence of any working example related to claimed invention and the no teaching in the prior art balanced only against the high skill level in the art, it is the position of the examiner that it would require undue experimentation for one of skill in the art to perform the method of the claim as broadly written.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Frank Lu, Ph. D., whose telephone number is (571)272-0746. The examiner can normally be reached Monday to Friday, 9 AM to 5 PM.
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/FRANK W LU/
Primary Examiner, Art Unit 1683
February 10, 2026