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 .
Election/Restriction
It is acknowledged that in response to the election requirement mailed 03/09/2026 that applicant elects Group 1 as set forth in the Office Action, which includes treating hydrocephalus as recited in original claim 16. Claims 1-17, 25, 35 and 41 have been cancelled without prejudice, and claims 45-64 have been added and are under examination.
Information Disclosure Statement
The information disclosure statement (IDS) filed 08/25/2023 has been considered and the references therein are of record.
The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
Claim Rejections - 35 USC § 112
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.
Claims 45-47, 49, 51-52, 55-58, and 62 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 45, 47, 49, 51-52, 55-58, and 62 are rejected for recitation of intended result/effect without conferring some structural or material difference on the scope of the claim. The claims recite the functional language of a melatonin agent without specifying any specific structures required to perform the functions. It is unclear as to what agents possess the required structure to perform the functions of melatonin activity (claims 45, 47, 49, 51-52, 55-58, & 62) and the function of inhibiting prolyl hydroxylase domain (claims 46-47 & 56). The requisite structure is merely implied by the functional language and thus the scope of the claim is undefined. Absent additional structure, it is unclear how these claims further limit the scope of the parent claim. MPEP 2173.05(g) states: “the use of functional language in a claim may fail ‘to provide a clear-cut indication of the scope of the subject matter embraced by the claim' and thus be indefinite.” It further states: “Examiners should consider the following factors when examining claims that contain functional language to determine whether the language is ambiguous: (1) whether there is a clear cut indication of the scope of the subject matter covered by the claim; (2) whether the language sets forth well-defined boundaries of the invention or only states a problem solved or a result obtained; and (3) whether one of ordinary skill in the art would know from the claim terms what structure or steps are encompassed by the claim.” The claims are rejected since they fail to meet all (3) criteria set forth in MPEP 2173.05(g).
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 45-58 and 62 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.
In making a determination of whether the application complies with the written description requirement of 35 U.S.C. 112, first paragraph, it is necessary to understand what Applicant has possession of and what Applicant is claiming. Claims 45-47, 49, 51-52, 55-58, and 62 recite, or are dependent upon, any agent capable of melatonin activity (claims 45, 47, 49, 51-52, 55-58, & 62) and inhibiting a prolyl hydroxylase domain (claims 46-47 & 56), each of which encompasses a genus of agents. Furthermore, claims 45-54 recite, or are dependent upon, the genera of methods of using the claimed composition to treat a subject that is susceptible to any and all species of hydrocephalus. These claims do not require that the genus of the claims possess any particular structure or other distinguishing feature that is characteristic of the genus as a whole. Therefore, the claims are drawn to genera of agents for which there is inadequate written description.
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 (see MPEP 2163(II)(3)(a)(i)(A), reduction to drawings MPEP 2163(II)(3)(a)(i)(B), or by disclosure of relevant, identifying characteristics, i.e., 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 applicant was in possession of the claimed genus MPEP 2163(II)(3)(a)(i)(C).
In the instant case, the only identifying characteristic present in the claim is a recitation of requisite melatonin activity, prolyl hydroxylase domain inhibition, and ability to treat a subject that is susceptible to hydrocephalus. From the specification, it is clear that Applicant is in possession of species listed in the Specification that fall within the genera of melatonin agents (pg. 16, 1st para.) and prolyl hydroxylase domain inhibitors (pg. 17, 2-3rd para.) that are capable of treating hydrocephalus. It is also clear from the specification that the applicant is not in possession of a method that is capable of treating a subject that is susceptible to hydrocephalus. The recitation of ‘treating a subject susceptible to hydrocephalus’ is synonymous to ‘preventing hydrocephalus’ since the claims require nothing more that the subject being capable of acquiring hydrocephalus, meaning that the Applicant would have to provide evidence of being able to prevent any and all hydrocephalus using the claimed composition and the specification provides no evidence of this.
Moreover, the claims are not limited to those species described in the specification and includes any possible agent capable of melatonin activity and prolyl hydroxylase domain inhibition that are further capable of preventing hydrocephalus. The specification fails to provide structures that are representative of species within each of the recited genera. Accordingly, in the absence of sufficient recitation of distinguishing identifying characteristics of the genus as a whole, or representative number of species within the genus, the specification does not provide adequate written description of the claimed genus.
Claims 45-58 and 62 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 the species listed in the Specification that fall within the genera of melatonin agents (pg. 16, 1st para.) and prolyl hydroxylase domain inhibitors (pg. 17, 2-3rd para.) that are capable of treating hydrocephalus, does not reasonably provide enablement for the vast genera of functions of melatonin activity (claims 45, 47, 49, 51-52, 55-58, & 62) and the function of inhibiting prolyl hydroxylase domain (claims 46-47 & 56) that are capable of treating hydrocephalus and also preventing hydrocephalus (claims 45-54). The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the invention commensurate in scope with these claims.
In AMGEN INC. ET AL. v. SANOFI ET AL. (No. 21-757, decided May 18, 2023), the Supreme Court held that Amgen was not enabled for “the entire genus” of antibodies that (1) “bind to specific amino acid residues on PCSK9,” and (2) “block PCSK9 from binding to [LDL receptors]” (872 F. 3d 1367, 1372) even though Amgen identified the amino acid sequences of 26 antibodies that perform these two functions.
The case law applies to the instant claims which require multiple genera of functional agents, yet the inventors have disclosed no requisite structure that must be present for each genus and have only disclosed use of Roxadustat and melatonin in treating hydrocephalus and the species listed in the specification.
In Amgen, the Supreme Court has stated:
“An antibody' s structure does much to dictate its function—its ability to bind to an antigen and, in some instances, to block other molecules in the body from doing the same. ‘For an antibody to bind to an antigen, the two surfaces have to fit together and contact each other at multiple points.' Id., at 11. But just because an antibody can bind to an antigen does not mean that it can also block. To bind and block, the antibody must establish a sufficiently broad, strong, and stable bond to the antigen. See ibid. Different antibodies have different binding and blocking capacities based on the amino acids that compose them and their three-dimensional shapes. See id., at 11–12.
Despite recent advances, aspects of antibody science remain unpredictable. For example, scientists understand that changing even one amino acid in the sequence can alter an antibody' s structure and function. See id., at 14. But scientists cannot always accurately predict exactly how trading one amino acid for another will affect an antibody' s structure and function. Ibid.”
A patent is granted for a completed invention, not the general suggestion of an idea and how that idea might be developed into the claimed invention. In the decision of Genentec, Inc., V. Novo Nordisk, 42 USPQ 2d 100, (CAFC 1997), the court held that: "[p]atent protection is granted in return for an enabling disclosure of an invention, not for vague intimations of general ideas that may or may not be workable" and that "[t]ossing out the mere germ of an idea does not constitute enabling disclosure". The court further stated that "when there is no disclosure of any specific starting material or of any of the conditions under which a process is to be carried out, undue experimentation is required; there is a failure to meet the enablement requirements that cannot be rectified by asserting that all of the disclosure related to the process is within the skill of the art","[i]t is the specification, not the knowledge of one skilled in the art, that must supply the novel aspects of an invention in order to constitute adequate enablement". The instant specification is not enabling for the full scope of the claimed invention because one cannot follow the guidance presented therein and practice the claimed method without first making a substantial inventive contribution.
Given that structure is essential to function; and given the unpredictability within the art with respect to creating antibodies, agonist, antagonists, and various other bioactive agents, a person having ordinary skill in the art would have to perform further experimentation in order to make the immense genera of agents with melatonin activity (claims 45, 47, 49, 51-52, 55-58, & 62) and prolyl hydroxylase domain inhibitors (claims 46-47 & 56) encompassed by the claims and then use them in the method claimed of preventing hydrocephalus, commensurate in scope with the breadth of the claims. Given the nature of the invention, a skilled artisan would have to make many agents, then use those in the method claimed in order to demonstrate making and using with a reasonable expectation of success. This amount of experimentation goes beyond what is considered “a reasonable degree of experimentation” and constitutes undue further experimentation in order to enable the method for the breadth of what is claimed.
Thus, claims 45-58 and 62 lack enablement.
Claim Rejections - 35 USC § 102
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.
Claims 45, 52, and 55 are rejected under 35 U.S.C. 102(a)(1)/(a)(2) as being anticipated by Robinson et al., 2018 (see instant PTO-892).
The instant claims are drawn to a method of treating a subject suffering from posthemorrhagic hydrocephalus by administering a composition that comprises melatonin.
Robinson teaches a method of treating a subject suffering from posthemorrhagic hydrocephalus by administering a composition that comprises melatonin (title & abstract).
Therefore, Robinson anticipates instant claims 45, 52, and 55.
Claim Rejections - 35 USC § 103
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 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.
Claims 45-59 are rejected under 35 U.S.C. 103 as being unpatentable over Robinson et al. 2018, as applied to claims 45, 52, and 55 above, in view of Kurata et al. 2019 (see instant PTO-892).
The instant claims are drawn to a method of treating posthemorrhagic hydrocephalus by co-administering a melatonin agent and a prolyl hydroxylase domain inhibitor. The instant claims are drawn to the prolyl hydroxylase domain inhibitor being FG4592 (Roxadustat), AKB-6548 (Vadadustat), TZ-951, GSK1278863 (Daprodustat), Bay85-3934 (Molidustat), or adaptaquin. The instant claims are drawn to the melatonin agent being melatonin.
The teachings of Robinson and how they meet the limitations of claims 45, 52, and 55 are outlined above in the preceding rejection and are hereby incorporated. Further, Robinson teaches a method of treating a subject suffering from posthemorrhagic hydrocephalus by administering a composition that comprises melatonin and erythropoietin (title & abstract).
Robinson does not explicitly teach a method of treating hydrocephalus by co-administering a melatonin and a prolyl hydroxylase domain inhibitor. Robinson does not explicitly teach the prolyl hydroxylase domain inhibitor being FG4592 (Roxadustat), AKB-6548 (Vadadustat), TZ-951, GSK1278863 (Daprodustat), Bay85-3934 (Molidustat), or adaptaquin.
Kurata teaches that prolyl hydroxylase domain inhibitors induce erythropoietin production (abstract). Kurata teaches that there are several PHD inhibitors, including Roxadustat, Vadadustat, Enardustat, Daprodustat, and Molidustat (abstract).
It would have been prima facie obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to arrive at the claimed invention from the disclosure of Robinson and Kurata. One with ordinary skill in the art would be motivated to make and use the claimed invention because in view of Robinson and Kurata an ordinary artisan would have found it obvious to use melatonin with prolyl hydroxylase domain (PHD) inhibitors to induce endogenous erythropoietin instead of administering an exogenous erythropoietin agent to treat post-hemorrhagic hydrocephalus. In the pursuit of optimizing the treatment, an ordinary artisan would have found it obvious that either endogenous erythropoietin production or exogenous erythropoietin administration could be used along with melatonin to treat hemorrhagic hydrocephalus and the treatment efficacy could be optimized by trying both options. The person of ordinary skill in the art would have had a reasonable expectation of success based on the disclosures of these prior art references. Thus, the claims do not contribute anything non-obvious over the prior art.
Claims 45-61 are rejected under 35 U.S.C. 103 as being unpatentable over Robinson et al. 2018 and Kurata et al. 2019, as applied to claims 45-59 above, in further view of Wikipedia, 2015 (see instant PTO-892).
Instant claims 45-59 are recited above. Instant claims 60-61 are drawn to the hydrocephalus being post-infectious hydrocephalus or post-traumatic hydrocephalus.
The teachings of Robinson and Kurata and how they meet the limitations of claims 45-59 are outlined above in the preceding rejections and are hereby incorporated. Neither of these references explicitly teach hydrocephalus being post-infectious hydrocephalus or post-traumatic hydrocephalus.
Wikipedia teaches that hydrocephalus can be acquired as a consequence of CNS infections, meningitis, brain tumors, head trauma, and intracranial hemorrhage (Causes, Acquired).
It would have been prima facie obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to arrive at the claimed invention from the disclosures of Robinson, Kurata, and Wikipedia. One with ordinary skill in the art would be motivated to make and use the claimed invention because Wikipedia teaches that there are various ways of acquiring hydrocephalus and an ordinary artisan would find it obvious that therefore the claimed invention could be applied to hydrocephalus irrespective of how it was acquired since the hydrocephalus is the consequence of various injuries. The person of ordinary skill in the art would have had a reasonable expectation of success based on the disclosures of these prior art references. Thus, the claims do not contribute anything non-obvious over the prior art.
Claims 45-64 are rejected under 35 U.S.C. 103 as being unpatentable over Robinson et al. 2018, Kurata et al. 2019, and Wikipedia 2015, as applied to claims 45-61 above, in further view of Wu et al. 2017 (US20170158690A1) (see instant PTO-892).
Instant claims 45-61 are recited above. Instant claims 62-64 are drawn to a kit comprising a melatonin agent in combination with Vadadustat or Roxadustat and instructions on using the kit to treat hydrocephalus. Instructions on using the kit do not hold patentable weight.
The teachings of Robinson, Jatzie, and Kurata and how they meet the limitations of claims 45-61 are outlined above in the preceding rejections and are hereby incorporated. None of these references explicitly teach a kit comprising a melatonin agent in combination with Vadadustat or Roxadustat.
Wu teaches a kit comprising therapeutic compositions for treatment of hydrocephalus (claims; para[0473]).
It would have been prima facie obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to arrive at the claimed invention from the disclosure of Robinson, Kurata, Wikipedia, and Wu. One with ordinary skill in the art would be motivated to make and use the claimed invention because an ordinary artisan would find it obvious to put the two components into a kit so that it can be readily used by an artisan to treat a subject with hydrocephalus. The person of ordinary skill in the art would have had a reasonable expectation of success based on the disclosures of these prior art references. Thus, the claims do not contribute anything non-obvious over the prior art.
Conclusion
No claims are allowed.
Advisory Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JOSEPH CESARE whose telephone number is (571)272-6908. The examiner can normally be reached Monday - Friday 10am-4pm.
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/JOSEPH D. CESARE/ Examiner, Art Unit 1675
/JEFFREY STUCKER/ Supervisory Patent Examiner, Art Unit 1675
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