DETAILED ACTION
Notice of Pre-AIA or AIA Status
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claim Status
2. Applicant’s correspondence filed June 30, 2023 is acknowledged; claims 1-20 are pending. Claims 17-10 are only rejected under 35 U.S.C. 101 and 35 U.S.C. 112(b) because they recite use of language, which is non-statutory subject matter.
Claim Rejections - 35 USC § 101
3. 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 17-20 are rejected under 35 U.S.C. 101 because the claimed invention is directed to non-statutory subject matter. The claim(s) does/do not fall within at least one of the four categories of patent eligible subject matter because they recite uses for the CCK-B receptor agonist, however a use does not fall within one of the four statutory categories of invention (i.e., process, machine, manufacture, or compositions of matter) as required by 35 U.S.C. 101. See MPEP 2106. Appropriate correction is required.
Claim Rejections - 35 USC § 112(a)
4. 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.
5. Claims 1-20 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 claims contain 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 states that the purpose of the written description requirement is to ensure that the inventor had possession, as of the filing date of the application, of the specific subject matter later claimed. 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.”
The written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, disclosure of drawings, or by disclosure of relevant identifying characteristics, for example, structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the Applicants were in possession of the claimed genus.
The instant claims are directed to methods for treating movement disorders comprising administering a CCK-B receptor agonist; wherein the movement disorders are caused by a condition selected from the group consisting of a brain injury, a stroke, Chorea, Dystonia, Parkinson's disease, brain infarction, neuron death or loss of neuronal plasticity due to aging (e.g., claim 2); and methods for regaining learning ability comprising administering a CCK-B receptor agonist (e.g., claim 10). The methods further recite various dosing regimens and timelines.
The specification provides examples of (i) characterizing CCK knockout or antagonism in the motor cortex (see FIGs. 1-5); (ii) treating movement disorders or motor learning defects caused by CCK knockout by administering a CCK-B receptor agonist (see FIGs. 6C-6E); and (iii) restoring neuronal plasticity defects caused by CCK knockout by administering a CCK-B receptor agonist (see FIGs. 6A-6B). No other experimental models suitable as a proxy for movement disorders were tested. However, the claims are directed to a genus of movement disorders far broader than single species of movement disorder (e.g., caused by CCK knockout or antagonism) supported by the examples.
The claims recite methods for treating a broad genera of movement disorders (including: brain injury, a stroke, Chorea, Dystonia, Parkinson's disease, brain infarction, neuron death or less of neuronal plasticity due to aging) and motor learning deficits. The specification only teaches a single example of treating a movement disorder, e.g., treating a movement disorder specifically caused by CCK knockout. However, the claims are not limited to a movement disorder or motor learning deficit caused by CCK knockout. The specification also provides no guidance as to what other movement disorders may be related to a CCK deficiency, and neither would a skilled person appreciate the claim-recited movement disorders to be related to a CCK deficiency. Therefore, the specification provides insufficient written description to support the genus encompassed by the claim. Vas-Cath Inc. v. Mahurkar, 19 USPQ2d 1111, makes clear that:
"applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the 'written description' inquiry, whatever is now claimed." (See page 1117.) The specification does not "clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed." (See Vas-Cath at page 1116.)
A skilled person would recognize CCK-B receptor agonism as effective for the treatment of Parkinson’s disease (e.g., Zhang, Zijuan, et al. "Neuroprotective effects of a cholecystokinin analogue in the 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine Parkinson’s disease mouse model." Frontiers in neuroscience 16 (2022): 814430.) at abstract); and for enhancing some forms of memory (e.g., “encoding sound-sound, visuoauditory, fear, and spatial memory”; instant specification at paragraph [0113]). However, it would not have been apparent that successfully treating a movement disorder caused by the artificial reduction of CCK in the motor cortex and having no know relevance to a disease state with a CCK-B receptor agonist (i.e., as demonstrated in the specification) may also predict the treatment of movement disorders with etiologies that may originate wholly outside the motor cortex. For example, Parkinson’s disease is caused by a loss of dopaminergic neurons in the substantia nigra, and cerebellar/brainstem stroke or infarct will also cause movement disorders. Therefore, there is no nexus between the instantly demonstrated rescue of CCK deficiencies in the motor cortex and treating neurological disorders only tangentially related to the motor cortex, as encompassed by the instant claims. Applicant also has not established any nexus that CCK abnormalities specifically exist in the relevant subject populations, e.g., subjects suffering from a “cryptogenic stroke” (e.g., claim 8), to establish possession of the claimed invention. In other words, a skilled person would have no reason to believe the claim-recited CCK-B receptor agonist treatments may beneficially treat the broad genus of movement disorders instantly claimed since the specification only demonstrates a single species of movement disorder: the treatment of a motor disorder specifically caused by CCK knockout.
Therefore, neither the art nor the specification provides a sufficient representative number of movement disorders to meet the written description requirements.
MPEP § 2163.02 states, “[a]n objective standard for determining compliance with the written description requirement is, 'does the description clearly allow person of ordinary skill in the art to recognize that he or she invented what is claimed’”. The courts have decided: the purpose of the "written description" requirement is broader than to merely explain how to "make and use"; the Applicant must convey with reasonable clarity to those skilled in the art, that as of the filing date sought, he or she was in possession of the invention. The invention is for purposes of the “written description” inquiry, whatever is now claimed. See Vas-Cath, Inc v. Mahurkar, 935 F.2d 1555, 1563-64, 19 USPQ2d 1111, 1117 (Federal Circuit, 1991).
Furthermore, the written description provision of 35 USC §112 is severable from its enablement provision; and adequate written description requires more than a mere statement that it is part of the invention and reference to a potential method for isolating it. Fiers v. Revel, 25 USPQ2d 1601, 1606 (CAFC 1993). And Amgen Inc. v. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016. Moreover, an adequate written description of the claimed invention must include sufficient description of at least a representative number of species by actual reduction to practice, reduction to drawings, or by disclosure of relevant, identifying characteristics sufficient to show that Applicant was in possession of the claimed genus. However, factual evidence of an actual reduction to practice has not been disclosed by Applicant in the specification; nor has Applicant shown the invention was “ready for patenting” by disclosure of drawings or structural chemical formulas that show that the invention was complete; nor has the Applicant described distinguishing identifying characteristics sufficient to show that Applicant were in possession of the claimed invention at the time the application was filed.
Therefore, for all these reasons the specification lacks adequate written description, and one of skill in the art cannot reasonably conclude that Applicant had possession of the claimed invention at the time the instant application was filed.
Claim Rejections - 35 USC § 112(b)
6. 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.
7. Claim 15, which depends from claim 10, recites the limitation "wherein the CCK-B receptor enables neuronal plasticity in motor cortex.” There is insufficient antecedent basis for this limitation in the claims because claim 10 only recites a method comprising “a step of administrating a CCK-B receptor agonist to a subject in need thereof.” Applicant may overcome the rejection by amending claim 15 to recite “CCK-B receptor agonist” in place of “CCK-B receptor.”
Claim 16, which depends from claim 10, recites the limitation "wherein the CCK-B receptor is effective in regaining motor learning ability in adulthood.” There is insufficient antecedent basis for this limitation in the claims because claim 10 only recites a method comprising “a step of administrating a CCK-B receptor agonist to a subject in need thereof.” Applicant may overcome the rejection by amending claim 16 to recite “CCK-B receptor agonist” in place of “CCK-B receptor.”
8. Claims 17-20 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 17-20 are drawn to the use of a CCK-B receptor agonist in the manufacture of a medicament for treating movement disorders; these claims are rendered indefinite by the recitation of the term “use.” The claims recite a “use” without setting forth any active, positive steps delimiting how this use is actually practice. Given that the claims do not set forth any steps involved in the method/process, it is unclear what method/process applicant is intending to encompass. See MPEP 2173.05(q). Clarification and/or correction is required.
Claim Rejections - 35 USC § 102
9. 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.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
10. Claims 1-7, 10-14, and 16-19 are rejected under 35 U.S.C. 102 (a)(1) as being anticipated by Zhang et al. (Zhang, Zijuan, et al. "Neuroprotective effects of a cholecystokinin analogue in the 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine Parkinson’s disease mouse model." Frontiers in neuroscience 16 (2022): 814430.)
Zhang et al. teaches the treatment of a MPTP Parkinson’s disease mouse model (i.e., a movement disorder) with a CCK8 analog (Abstract). The CCK8 analog is a CCK-B receptor agonist, e.g., “CCKR-2 [i.e., the CCK-B receptor] is predominantly expressed in the brain and is activated by short fragments such as CCK-8” (page 2, left column, first paragraph). Accordingly, Zhang et al teaches a method for treating movement disorders comprising a step of administrating a CCK-B receptor agonist to a subject in need thereof, wherein the movement disorders are caused by a condition selected from the group consisting of a brain injury, a stroke, Chorea, Dystonia, Parkinson's disease, brain infarction, neuron death or less of neuronal plasticity due to aging, and a combination thereof (claims 1 and 2).
Zhang et al. teaches a CCK8 analog. however, a CCK8 analog is also a CCK4 analog. Applicant’s specification at paragraph [0052] describes CCK4 analogs as:
The CCK4 analogues may have structures similar to CCK4, and thus we can expect similar functions. It is believed that the main structure of CCK4 (Trp-Met-Asp-Phe-NH2) is the most critical part, some modifications for C-terminal, N-terminal or both to protect the stability or activity, or replacement of the sulfhydryl in Met with other radical without changing the backbone of the molecule may lead to analogues having similar functions as CCK4 itself. In some embodiment, the CCK-B receptor agonist is CCK4. Without intending to be bound by theory, it is believed that CCK4 can pass through the brain-blood barrier, may have fewer side effects and high efficiency with low dosage. In contrast, it is believed that other types of CCK peptides including CCK58, CCK32, and CCK8 cannot pass through the brain-blood barrier.
The specification therefore defines CCK4 analogs as having similar structure (especially the main structure) to CCK4 and by having similar functions to CCK4 (e.g., CCK-B receptor agonism and able to pass through the blood-brain barrier). The CCK8 of Zhang et al. definitively meets all of these criteria.
CCK8 is a CCK4 analog within the meaning of Applicant’s specification because (i) it shares the same main structure (Trp-Met-Asp-Phe-NH2) with CCK4 (see Zhang et al. at page 2, “Peptides and Chemicals”); (ii) it is an agonist of the CCK-B receptor like CCK4 (see above); and it can pass through the brain-blood barrier contrary to Applicant’s assertion in the specification, e.g., “[t]he CCK[8] analogue carboxyfluorescein can cross the BBB and is abundantly expressed in the substantia nigra and striatum” (page 4, “Assessment of CCK Analogue”). Therefore, Zhang et al. anticipates the claim-recited CCK4 analog (claim 3).
Zhang et al. further teaches administering the CCK-B receptor agonist intraperitoneally, e.g., “CCK-AC were injected at 50 nmol/kg ip” (page 2, “Assessment of Cholecystokinin”) (claim 4). Zhang et al. further teaches administering the CCK-B receptor agonist over a period of two weeks (Figure 2A) (claim 5). Zhang et al. further teaches administering the CCK-B receptor agonist at 50 nmol/kg (page 2, “Assessment of Cholecystokinin”). The common Trp-Met-Asp-Phe-NH2 sequence of Applicant’s CCK4 and Zhang’s CCK8 analog has a peptide molecular weight of about 596.71 g/mol, and so 50 nmol/kg converts1 to a dosage of about 0.0298 mg/kg of the CCK4 Trp-Met-Asp-Phe-NH2 sequence (claim 6).
Zhang et al. further teaches the CCK-B receptor agonist is effective in regaining motor learning ability in adulthood. More specifically, Zhang et al. teaches that a CCK-B receptor agonist “significantly reversed” the “impairments in muscular strength and movement balance” induced by the MPTP Parkinson’s disease model (page 4, right column, first paragraph). The specific methodology employed demonstrates that this reversal is an improvement in motor learning rather than mere physical recovery because the rotarod test “was used to assess the balance and motor coordination ability of mice,” and notably, the “mice were trained for 3 min every day, lasting for three consecutive days” (page 3, Behavioral Tests, Rotarod). Per the experimental timeline in Figure 2A, this training occurred between days 12 and 14, subsequent to the administration of MPTP. Because the subjects acquired the coordination necessary for the rotarod test only after the establishment of the movement disorder, their performance represents the successful acquisition of a new motor skill. The CCK-B receptor agonist-treated mice therefore regained motor learning ability because the loss of such ability was “significantly reversed” (Figure 2D) relative to the MPTP-only control. Finally, Zhang et al. teaches this effect in maturity, as the “subjects” were 2-month-old adult mice (page 2) (claim 7). The aforementioned passages also teach the method of claims 10-14 and 16, directed to methods of regaining motor learning ability having the same limitations as claims 3-7.
Conclusion
11. No claim is allowed.
12. Any inquiry concerning this communication or earlier communications from the examiner should be directed to BRANDON R SCHWECHTER whose telephone number is (571)272-1270. The examiner can normally be reached M-Th 7-5 EST.
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, Vanessa Ford can be reached at 20857. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/BRANDON R SCHWECHTER/
Examiner, Art Unit 1674
/VANESSA L. FORD/ Supervisory Patent Examiner, Art Unit 1674
1 To convert a dose of 50 nmol/kg for a peptide having a molecular weight of 596.71 g/mol into mg/kg, the molar concentration is multiplied by the molecular weight and adjusted for unit scale. Specifically, the dose of 50 x 10-9 mol/kg is multiplied by 596.71 g/mol, resulting in a mass of 2.98355 x 10-5 g/kg. To convert this value from grams to milligrams, it is multiplied by 1,000, which yields a final mass-based concentration of 0.0298 mg/kg.