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 (i.e., changing from AIA to pre-AIA ) 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.
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code, note p25, line 28. 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.
Drawings
The drawings are objected to because figs 1 (all panels), 3E, 5C, and fig 12 B-E are illegible, and figs 2, 5D, 5E, and 12 C-F require color. Applicants are required to correct these issues. If applicant is not able to show what is necessary in greyscale, they can petition for color drawings. 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.
Election/Restrictions
Applicant’s election without traverse of group I (polypeptides) and SEQ ID 3 in the reply filed on 27 April, 2026 is acknowledged.
The requirement is deemed proper and is therefore made FINAL.
Applicants have elected SEQ ID 3. A search was conducted for this invention, and it was determined to be novel and unobvious over the prior art. The closest prior art found is the native sequence (UniProt entry for human KIF7, entry version 129 (Aug 2020)), which comprises SEQ ID 3. However, that sequence is considerably longer than 170 amino acids in length, nor is there any reason given in this or any other reference to mutate the sequence to that length or shorter while comprising SEQ ID 3. Thus, the claimed sequence is both novel and unobvious over the prior art. However, non-prior art rejections apply, so claims 1-3 and 10 were examined and claims 4-9, 11, and 13-16 were withdrawn from consideration. While applicants state that they believe claims 4-6 read on their elected species, claims 4 and 6 require additional components not elected by applicants (these claims are not anticipated by SEQ ID 3), and claim 5 requires a mutated variant of SEQ ID 3. Thus, these claims are properly withdrawn.
Claims Status
Claims 1-11 and 13-16 are pending.
Claims 4-9, 11, and 13-16 have been withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention or species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 27 April, 2026.
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 1-3 and 10 are rejected under 35 U.S.C. 101 because they read on a judicial exception (natural phenomenon).
The Supreme Court has given a 2 part test to determine eligibility under this statute:
1) Are the claims drawn to a process, machine, manufacture, or composition of matter?
2a) If step 1 is passed, does a judicial exception apply?
2b) If a judicial exception applies, is there anything beyond the judicial exception?
Applying the test:
1) The claims are drawn to polypeptides, a composition of matter, passing the first test.
2a) The UniProt entry for human KIF7 (entry version 129 (Aug 2020)) shows that SEQ ID 3, which reads on claims 1-3, is a fragment of this naturally occurring polypeptide (position 481-543). Note that in Ass’n for Molecular Pathology v Myriad Genetics (569 U.S. 576), the Supreme Court stated that isolated DNA is a natural phenomenon, even though the gene was truncated from the chromosome. Following this precedent, fragments of a naturally occurring polypeptide are considered to be natural phenomenon as well, unless there is something beyond the judicial exception. Claim 10 requires a carrier, but this can be met with naturally occurring compounds, such as water.
2b) Claims 1-3 can be met with merely the polypeptide. There is no evidence on record that truncating the full length polypeptide provides significantly different properties. As there is nothing other than the polypeptide in these embodiments, there can be nothing beyond the polypeptide. Claim 10 requires a carrier, but there is no evidence of record that a carrier will give the sequence properties that would give the composition something beyond just the polypeptide. Thus, the claims lack eligibility under this statute.
Claim Rejections - 35 USC § 112(a)
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.
Claims 1-3 and 10 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
The MPEP lists factors that can be used to determine if sufficient evidence of possession has been furnished in the disclosure of the application. These include "level of skill and knowledge in the art, partial structure, physical and/or chemical properties, functional characteristics alone or coupled with a known or disclosed correlation between structure and function, and the method of making the claimed invention. Disclosure of any combination of such identifying characteristics that distinguish the claimed invention from other materials and would lead one of skill in the art to the conclusion that the applicant was in possession of the claimed species is sufficient" (MPEP 2163).
A claimed genus may be satisfied through sufficient description of a representative number of species or disclosure of relevant, identifying characteristics such as functional characteristics coupled with a known or disclosed correlation between function and structure(MPEP 2163(3)a(II)). The number of species that describe the genus must be adequate to describe the entire genus; if there is substantial variability, a large number of species must be described.
The analysis for adequate written description considers (a) actual reduction to practice, (b) disclosure of drawings or structural chemical formulas, (c) sufficient relevant identifying characteristics in the way of complete/partial structure or physical and/or chemical properties or functional characteristics when coupled with known or disclosed correlation with structure and (d) representative number of samples.
(a and b) actual reduction to practice and disclosure of drawings or structural chemical formulas: Applicants have demonstrated that the coil-coiled domain of KIF7 binds to Gli2 at the DNA binding site, with an electrostatic involvement in binding (p13, line 4-14). Extensive computer modeling was used to examine the interaction, including computational alanine mutation studies (p13, line 22-36).
(c) sufficient relevant identifying characteristics in the way of complete/partial structure or physical and/or chemical properties or functional characteristics when coupled with known or disclosed correlation with structure: The rejected claims require a peptide that folds into a coiled/coil domain, and exploits DNA mimicry to engage Gli, with dependent claims requiring some level of identity with SEQ ID 3. This requires that any sequence that meets the claim limitations must have the functional ability to 1) fold into a coil coiled domain 2) mimic DNA and 3) engage Gli. However, a person of skill in the art, armed with applicant’s disclosure, would not know what structural features are required to meet these functional limitations. Such an individual would not know what sequence/charge/hydrophobicity requirement are necessary to meet the functional requirements of the claims. In essence, applicants are defining their claimed material by function. That is not sufficient to meet the written description requirement.
Howes (C&ENews, Dec 2020) discusses DeepMind AI, which predicted protein structures (title). Prior to this software, prediction techniques could not compute a structure that matched experimental data for an amino acid sequence (1st page, 3d paragraph). AlphaFold computed about two thirds of the protein structures within experimental error (1st page, 4th paragraph). This reference shows that, prior to Dec, 2020, it was not possible to compute a structure – such as a coiled coil structure -- from an amino acid sequence.
As of applicant’s priority date, it was not possible to predict if a given molecule bound to a protein. Lowe (blog “In the pipeline” entry of 7 Sept, 2022) describes an experiment where that was attempted. 39K compounds, including known antibiotics, were screened against E. coli for growth inhibition, finding 218 active compounds (1st page, 3d paragraph). These were computer docked to a set of 296 essential bacterial proteins by multiple docking procedures (1st page, 3d paragraph), along with 100 random inactive compounds (2nd page, 1st paragraph). The number of strong binders predicted were essentially the same between the active compounds and the controls, and out of 142 compound/target interactions previously known, the methodology found only 3 (2nd page, 2nd paragraph). While a given docking program may accurately predict if compound A binds to protein B, it is impossible to a priori know if the prediction is accurate. In other words, several years after applicant’s priority date, it was not possible to predict if a given compound and target bound to each other. Note that almost all of applicant’s data is computational, without other experimentation to confirm the computer model. However, as Lowe shows, roughly 2 years after applicant’s priority date, such modeling cannot be relied upon to give accurate information. Note that much of applicant’s work is based on computer modeling, without any verification of the results of the model.
Nor is it possible to modify known sequences to reliably find new compounds. Guo et al (PNAS (2004) 101(25) p9205-9210) looked at the effect of random mutations (title). In a DNA repair enzyme, about one mutation in three killed the activity of the protein, consistent with studies with other proteins (abstract). Yampolsky et al (Genetics (2006) 170 p1459-1472), using a different methodology, found that even conservative substitutions were prone to problems (table 3, p1465, top of page). In other words, unless there is some information known about the binding, mutating the sequence is likely to be detrimental, making it a poor way to generate new compounds.
(d) representative number of samples: Applicants have used human KIF7 and a truncated version of the polypeptide (SEQ ID 3). Given that the only structural information in the independent claim is 170 amino acids or less, with no limitation that the amino acids all be naturally occurring, there are an infinite number of structures that meet the structural limitations of the claims. Given that it is not possible to modify a known structure to reliably give structures with similar properties, it is not possible to extrapolate from applicant’s experiments to the entire genus described by the claims. Thus, the claims lack written description.
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.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
first rejection
Claims 1-3 and 10 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 1, and claims dependent on it requires that the sequence exploit DNA mimicry. It is not clear what this means. It could mean some level of structural similarity to a DNA sequence (such as glycosylation or charge), it could mean anything that binds to a DNA binding portion of a polypeptide, or something else.
In addition, the polypeptide must “engage” Gli. It is not clear what this means. It could mean binds to Gli, it could mean an agonist to Gli, it could mean influences Gli (such as the salt in the charge experiment of applicants, p13, line 10-14), without requiring actual contact, or some other meaning.
second rejection
Claims 2 and 3 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claims 2 and 3 require that the sequence is substantially identical to either the coiled coil dimerization domain of KIF7 (assumed to be residues 480-542) for claim 2 or SEQ ID 3 for claim 3. “Substantially identical” is defined as at least 40%, 50%, 60%, 70%, 80%, 90% or even 95%, 97%, or 99% sequence identity to a reference sequence (p4, line 5-6). However, given the multiple cutoffs in the definition, it is not clear what the cutoff is for a sequence that is substantially identical to another sequence.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to FRED REYNOLDS whose telephone number is (571)270-7214. The examiner can normally be reached M-Th 9-3:30.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Melissa Fisher can be reached at 571-270-7430. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/FRED H REYNOLDS/Primary Examiner, Art Unit 1658
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