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 .
DETAILED ACTION
Claim Status
This action is in response to the amended claims filed on 10/01/2024. Claims 1-20 are pending and are considered on the merits. Claims 1, 4, 5, 7 and 9 are independent claims.
Priority
This application is a 371 of PCT/CN22/84779 (filed on 04/01/2022). The priority claim of the instant application has been granted and the earliest benefit date is 04/01/2022 from the application PCT/CN22/84779.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 10/01/2024, 11/04/2024, 02/20/2026 and 05/12/2026 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner. The corresponding signed and initialed PTO forms 1449 have been mailed with this action.
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 9-14 and 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.
Claim 9, claim 11 and claim 12 all recite the term “preferably”, which renders the claim indefinite because it is a subjective term. A claim that requires the exercise of subjective judgment without restriction may render the claim indefinite. See MPEP § 2173.05(b).
Additionally, claim 12 recites the term “elderly”. A claim may be rendered indefinite by reference to term of an object that is variable (see MPEP 2173.05(b), II). Specifically, the term “elderly” is a relative term that is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. It is noted that the closest disclosure in the specification is that “The elderly can be a person at or over 60 years old, at or over 65 years old, at or over 70 years old, at or over 75 years old, or at or over 80 years old” (p. 9, lines 23-24).
Claim 10 contains the trade name “Lepalvir”. Where a trademark or trade name is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph. See Ex parte Simpson, 218 USPQ 1020 (Bd. App. 1982). The claim scope is uncertain since the trademark or trade name cannot be used properly to identify any particular material or product. A trademark or trade name is used to identify a source of goods, and not the goods themselves. Thus, a trademark or trade name does not identify or describe the goods associated with the trademark or trade name. In the present case, the trade name Lepalvir is used to identify/describe extracts from rabbit skin inflamed by vaccinia virus for injection, which is a therapeutic biological product containing a variety of small molecular peptides extracted from rabbit skin inflamed by vaccinia virus for injection (see Vanworld Pharmaceutical (Rugao) Company Limited. Accordingly, the identification/description is indefinite.
Claims 13-14 and claims 17-20 all recite unit of the extract from rabbit skin inflamed by vaccinia virus (e.g., “U/kg” in claims 13 and 17-18, and “U” in claims 14 and 19-20). A claim may be rendered indefinite by reference to term of an object that is variable (see MPEP 2173.05(b), II). Specifically, the term “unit” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. To the extent that the specification does not provide a special definition on the term “unit”, prior art is treated as enabling as the instant invention. Thus, prior art Lau (WO2020/211009) is used to teach the units of the extract from rabbit skin inflamed by vaccinia virus (see below).
Claim Rejections - 35 USC § 112(a)
(Written Description)
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 1-20 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 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 pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
Under the written description guidelines (see MPEP 2163) the Examiner is directed to determine whether one skilled in the art would recognize that the Applicant was in possession of the claimed invention as a whole at the time of filing. The following considerations are critical to this determination.
To satisfy the written description requirement, a patent specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention. See, e.g., Moba, B.V. v. Diamond Automation, Inc., 325 F.3d 1306, 1319, 66 USPQ2d 1429, 1438 (Fed. Cir. 2003); Vas-Cath, Inc. v. Mahurkar, 935 F.2d at 1563, 19 USPQ2d at 1116. An original claim may lack written description support when (1) the claim defines the invention in functional language specifying a desired result but the disclosure fails to sufficiently identify how the function is performed or the result is achieved or (2) a broad genus claim is presented but the disclosure only describes a narrow species with no evidence that the genus is contemplated. See Ariad Pharms., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1349-50 (Fed. Cir. 2010) (en banc). The written description requirement is not necessarily met when the claim language appears in ipsis verbis in the specification. Enzo Biochem, Inc. v. Gen-Probe, Inc., 323 F.3d 956, 968, 63 USPQ2d 1609, 1616 (Fed. Cir. 2002).
In the present case, the claimed invention encompasses (1) a genus of method for preventing or treating, encompassing completely curing, Alzheimer’s disease (see claim 1 and dependent claims); and (2) a genus of extract from rabbit skin inflamed by vaccinia virus (see claims 1-20). Thus, the Applicant needs to demonstrate the possession at the time of filing that, (1) the claimed method can predictably prevent or cure Alzheimer’s disease in claim 1; and (2) any extract from rabbit skin inflamed by vaccinia virus can predictably perform the claimed methods in claims 1, 4, 5, 7 and 9.
SCOPE OF THE INVENTION
Independent Claim 1 encompasses (1) a genus of method for preventing or treating, encompassing completely curing, Alzheimer’s disease; and (2) by administering a genus of extract from rabbit skin inflamed by vaccinia virus.
Independent Claims 4, 5, 7 and 9 encompass therapeutic methods comprising administering a genus of extract from rabbit skin inflamed by vaccinia virus.
Dependent claims 2-3, 6, 8 and 10-20 encompass the results and mechanisms of the method, and defined glial cells, inflammatory factors, formulation and dosage of the extract, and the patient.
However, the specification only discloses the neuroprotective effects of Lepalvir on the APP/PS1 mouse model of Alzheimer's disease (see p. 11, Example 1).
In regard to the genus of method for preventing or curing, Alzheimer’s disease encompassed by claim 1, the specification only discloses a method for alleviating or reducing β-amyloid plaque deposition in the brain of a patient suffering from Alzheimer's disease, a method for alleviating or reducing inflammatory response of glial cells in the brain of a patient suffering from Alzheimer's disease, a method for alleviating or reducing the expression or level of inflammatory factors in the brain of a patient suffering from Alzheimer's disease, and a method for improving, enhancing or restoring cognitive functions or cognitive abilities in a patient suffering from Alzheimer's disease (i.e., in claims 4, 5, 7 and 9).
In regard to administering a genus of extract from rabbit skin inflamed by vaccinia virus encompassed by claims 1, 4, 5, 7 and 9, the specification only discloses one single species of the extract, Lepalvir, administered through injection.
ACTUAL REDUCTION TO PRACTICE
Accordingly, Applicant did not demonstrate a reduction to practice a genus of method for preventing or treating, encompassing completely curing, Alzheimer’s disease encompassed by claim 1, or a reduction to practice a genus of extract from rabbit skin inflamed by vaccinia virus encompassed by claim 1, 4, 5, 7 and 9, nor did Applicant adequately set forth in terms of distinguishing identifying characteristics as evidenced by other descriptions of the invention that are sufficiently detailed to show that Applicant was in possession of the claimed genus of method.
DISCLOSURE OF STRUCTURE
The Applicant has provided no working examples for preventing or completely curing Alzheimer’s disease, and only provided a single working example for injecting one species of the extract. Although Alzheimer’s disease has been studied, the prior art, even post art, is silent on a method of preventing or completely curing Alzheimer’s disease, or a method of administering any extract from rabbit skin inflamed by vaccinia virus, nor indicate a relationship between the structure of the claimed extract and the ability to use in the claimed methods.
SUFFICIENT RELEVANT IDENTIFYING CHARACTERISTICS
The breadth of the claims encompasses (1) a genus of method for preventing or completely curing, Alzheimer’s disease; and (2) by administering a genus of extract from rabbit skin inflamed by vaccinia virus, yet the present specification provides no guidance nor description on (1) how the Alzheimer’s disease is prevented or completely cured, or (2) how administration of any extract from rabbit skin inflamed by vaccinia virus would result in the therapeutic effects in claims 1, 4, 5, 7 and 9.
Therefore, the skilled artisan would not know what rational approach to take to use the claimed method of preventing or completely curing Alzheimer’s disease or to use the claimed extract from rabbit skin inflamed by vaccinia virus. Thus, it is incumbent on the applicant to provide this nexus between structure and function, in order to be given credit for possession of the claimed genus of method and extract. Otherwise, the Written Description guidelines suggest that the applicant is entitled to only the species specifically recited as having this activity. Moreover, even when several species are disclosed, these are not necessarily representative of the entire genus. AbbVie Deutschland GMBH v. Janssen Biotech, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014). Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus to provide a "representative number” of species.
An applicant may show that an invention is complete by disclosure of sufficiently detailed, relevant identifying characteristics which provide evidence that applicant was in possession of the claimed invention, i.e., complete or partial structure, other physical and/or chemical properties, functional characteristics when coupled with a known or disclosed correlation between function and structure, or some combination of such characteristics. Enzo Biochem, 323 F.3d at 964, 63 USPQ2d at 1613.
STATE OF THE ART & QUANTITY OF EXPERIMENTATION
The method of using the claimed invention is not well established. Although the method for alleviating a symptom associated with Alzheimer’s disease or a method for making extract from rabbit skin was known in the state of the art, one of skill in the art would neither expect nor predict the method may prevent or completely cure Alzheimer’s disease, or the method may alleviate a symptom by administrating any extract from rabbit skin.
In regard to (1) a genus of method for preventing or completely curing, Alzheimer’s disease (claim 1), post filing art NIA (Preventing Alzheimer's Disease: What Do We Know?, published October 10, 2023, downloaded on 7/6/26, downloaded from https://www.nia.nih.gov/health/alzheimers-and-dementia/preventing-alzheimers-disease-what-do-we-know, p. 1-5) teaches “nothing has been proven yet to prevent Alzheimer’s” (p. 1, lines 2-3) and teaches “Be cautious about Alzheimer's "cures"” (p. 4, last section). Consequently, there is ample reason to conclude that there would be a high degree of unpredictability in preventing or curing Alzheimer’s disease.
In regard to (2) a genus of extract from rabbit skin inflamed by vaccinia virus (claims 1, 4, 5, 7 and 9), post filing art Toniasso et al., (Food Research International. 2022;162:111967, p. 1-10) teaches a method of making collagen extracted from rabbit skin to add value to the by-product (see e.g., abstract), thus teaches the extract from rabbit skin may include high-purity collagen, which could likely be extracted from rabbit skin inflamed by vaccinia virus as well. In other words, the genus of extract from rabbit skin inflamed by vaccinia virus in the instant claims encompasses high-purity collagen. Consequently, there is ample reason to conclude that there would be a high degree of unpredictability in performing the methods recited in claims 1, 4, 5, 7 and 9 by administering collagen.
CONCLUSION
Therefore, the Examiner concludes that there is insufficient written description of the instantly claimed genus of method for preventing or completely curing Alzheimer’s disease, or the genus of extract from rabbit skin inflamed by vaccinia virus. Specifically, there is limited description of the method for preventing or completely curing Alzheimer’s disease in claim 1, and limited description of the structure-function relationship between the claimed genus of extract from rabbit skin inflamed by vaccinia virus and their ability to perform the methods in claims 1, 4, 5, 7 and 9. The Examiner further concludes a skilled artisan would find the specification inadequately describes the claimed genus of method and extract as discussed above.
Therefore, the specification fails to provide sufficient written description to inform a skilled artisan that inventors were in possession of the entire scope of the claimed invention.
(Scope of Enablement)
Claims 1-20 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 a method for alleviating or reducing β-amyloid plaque deposition in the brain of a patient suffering from Alzheimer's disease, a method for alleviating or reducing inflammatory response of glial cells in the brain of a patient suffering from Alzheimer's disease, a method for alleviating or reducing the expression or level of inflammatory factors in the brain of a patient suffering from Alzheimer's disease, and a method for improving, enhancing or restoring cognitive functions or cognitive abilities in a patient suffering from Alzheimer's disease (i.e., in claims 4, 5, 7 and 9), by injecting Lepalvir that is an extract from rabbit skin inflamed by vaccinia virus (see specification, Example 1), does not reasonably provide enablement for a method of preventing or curing Alzheimer’s disease, or enablement for administering any extract from rabbit skin inflamed by vaccinia virus in the above methods. 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.
The factors to be considered in determining whether undue experimentation is required are summarized In re Wands 858 F.2d 731, 8 USPQ2nd 1400 (Fed. Cir, 1988). The Court in Wands states: “Enablement is not precluded by the necessity for some 'experimentation.'” Clearly, enablement of a claimed invention cannot be predicated on the basis of quantity of experimentation required to make or use the invention. “Whether undue experimentation is needed is not a single simple factual determination, but rather is a conclusion reached by weighing many factual considerations.” (Wands, 8 USPQ2d 1404). The factors to be considered in determining whether undue experimentation is required include: (1) the quantity of experimentation necessary, (2) the amount or 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. While all of these factors are considered, a sufficient amount for a prima facie case is discussed below.
The office has analyzed the specification in direct accordance to the factors outlined in In re Wands. MPEP 2164.04 states: "[W]hile the analysis and conclusion of a lack of enablement are based on factors discussed in MPEP 2164.01(a) and the evidence as whole, it is not necessary to discuss each factor in written enablement rejection." These factors will be analyzed, in turn, to demonstrate that one of ordinary skill in the art would have had to perform "undue experimentation" to make and/or use the invention and therefore, Applicant's claims are not enabled commensurate with the scope of the invention.
SCOPE OF THE INVENTION
Independent Claim 1 encompasses (1) a genus of method for preventing or treating, encompassing completely curing, Alzheimer’s disease; and (2) by administering a genus of extract from rabbit skin inflamed by vaccinia virus.
Independent Claims 4, 5, 7 and 9 encompass therapeutic methods comprising administering a genus of extract from rabbit skin inflamed by vaccinia virus.
Dependent claims 2-3, 6, 8 and 10-20 encompass the results and mechanisms of the method, and defined glial cells, inflammatory factors, formulation and dosage of the extract, and the patient.
However, the specification only discloses the neuroprotective effects of Lepalvir on the APP/PS1 mouse model of Alzheimer's disease (see p. 11, Example 1).
In regard to the genus of method for preventing or curing, Alzheimer’s disease encompassed by claim 1, the specification only discloses a method for alleviating or reducing β-amyloid plaque deposition in the brain of a patient suffering from Alzheimer's disease, a method for alleviating or reducing inflammatory response of glial cells in the brain of a patient suffering from Alzheimer's disease, a method for alleviating or reducing the expression or level of inflammatory factors in the brain of a patient suffering from Alzheimer's disease, and a method for improving, enhancing or restoring cognitive functions or cognitive abilities in a patient suffering from Alzheimer's disease (i.e., in claims 4, 5, 7 and 9).
In regard to administering a genus of extract from rabbit skin inflamed by vaccinia virus encompassed by claims 1, 4, 5, 7 and 9, the specification only discloses one single species of the extract, Lepalvir, administered through injection.
ACTUAL REDUCTION TO PRACTICE
Accordingly, Applicant did not demonstrate a reduction to practice a genus of method for preventing or treating, encompassing completely curing, Alzheimer’s disease encompassed by claim 1, or a reduction to practice a genus of extract from rabbit skin inflamed by vaccinia virus encompassed by claim 1, 4, 5, 7 and 9, nor did Applicant adequately set forth in terms of distinguishing identifying characteristics as evidenced by other descriptions of the invention that are sufficiently detailed to show that Applicant was in possession of the claimed genus of method.
STATE OF THE ART & QUANTITY OF EXPERIMENTATION
The method of using the claimed invention is not well established. Although the method for alleviating a symptom associated with Alzheimer’s disease or a method for making extract from rabbit skin was known in the state of the art, one of skill in the art would neither expect nor predict the method may prevent or completely cure Alzheimer’s disease, or the method may alleviate a symptom by administrating any extract from rabbit skin.
In regard to (1) a genus of method for preventing or treating, encompassing completely curing, Alzheimer’s disease (claim 1), post filing art NIA (Preventing Alzheimer's Disease: What Do We Know?, published October 10, 2023, downloaded from https://www.nia.nih.gov/health/alzheimers-and-dementia/preventing-alzheimers-disease-what-do-we-know, downloaded on 7/6/26, p. 1-5) teaches “nothing has been proven yet to prevent Alzheimer’s” (p. 1, lines 2-3) and teaches “Be cautious about Alzheimer's "cures"” (p. 4, last section). Consequently, there is ample reason to conclude that there would be a high degree of unpredictability in preventing or curing Alzheimer’s disease.
In regard to (2) a genus of extract from rabbit skin inflamed by vaccinia virus (claims 1, 4, 5, 7 and 9), post filing art Toniasso et al., (Food Research International. 2022;162:111967, p. 1-10) teaches a method of making collagen extracted from rabbit skin to add value to the by-product (see e.g., abstract), thus teaches the extract from rabbit skin may include high-purity collagen, which could likely be extracted from rabbit skin inflamed by vaccinia virus as well. In other words, the genus of extract from rabbit skin inflamed by vaccinia virus in the instant claims encompasses high-purity collagen. Consequently, there is ample reason to conclude that there would be a high degree of unpredictability in performing the methods recited in claims 1, 4, 5, 7 and 9 by administering collagen.
Since even the post-filing art after the effective filing date of the present application did not provide guidance for preventing or completely curing Alzheimer’s disease, or guidance for using any extract from rabbit skin inflamed by vaccinia virus in the methods of instant claims, it is incumbent upon the instant specification to do so. The physiological art is recognized as unpredictable (MPEP 2164.03). As set forth in In re Fisher, 166 USPQ 18 (CCPA 1970), compliance with 35 USC 112, first paragraph requires: “That scope of claims must bear a reasonable correlation to scope of enablement provided by specification to persons of ordinary skill in the art; … in cases involving unpredictable factors, such as most chemical reactions and physiological activity, scope of enablement varies inversely with degree of unpredictability of factors involved.” Moreover, the courts have also stated that reasonable correlation must exist between scope of exclusive right to patent application and scope of enablement set forth in the patent application (27 USPQ2d 1662 Ex parte Maize!.). In view of the foregoing, due to the lack of sufficient guidance provided by the specification regarding the issues set forth above, the state of the relevant art, and the breadth of the claims, it would have required undue experimentation for one skilled in the art to use the instant broadly claimed invention.
CONCLUSION
In conclusion, since the art teaches that the method for preventing or curing Alzheimer’s disease, or using any extract from rabbit skin inflamed by vaccinia virus in the instant claimed methods, is prone to influence by multiple factors, and is highly unpredictable, and the specification does not provide ample guidance, one would be burdened with undue experimentation to use the claimed invention for preventing or curing Alzheimer’s disease, or to administer any extract from rabbit skin inflamed by vaccinia virus in the above methods.
In conclusion, given the breadth of the claims and the limited scope of the specification, an undue quantity of experimentation is required to use the invention beyond the scope of a method for alleviating or reducing β-amyloid plaque deposition in the brain of a patient suffering from Alzheimer's disease, a method for alleviating or reducing inflammatory response of glial cells in the brain of a patient suffering from Alzheimer's disease, a method for alleviating or reducing the expression or level of inflammatory factors in the brain of a patient suffering from Alzheimer's disease, and a method for improving, enhancing or restoring cognitive functions or cognitive abilities in a patient suffering from Alzheimer's disease (i.e., in claims 4, 5, 7 and 9), by administering Lepalvir or Neurotropin that is an extract from rabbit skin inflamed by vaccinia virus.
Examiner’s comment
Based on the limited scope enabled by Applicant’s specification (see above), the prior art Liu and Lau have been applied to anticipate and make obvious this limited scope of method.
Claim Rejections - 35 USC § 102
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.
Claims 1-9, 11 and 15-16 are rejected under 35 U.S.C. 102 (a)(1) as being anticipated by Liu et al., (WO2020/154941 A1).
With respect to independent claim 1, Liu teaches a method for alleviation, progression control or treatment of Alzheimer's disease (e.g., p. 2, lines 7-8 from bottom) by administering Neurotropin (NTP), which is a well-known analgesic derived from inflamed rabbit skin inoculated with vaccinia virus with beneficial results (e.g., p. 6, para 1 for administering, p. 1 for describing “NTP” and p. 8, section (9) for “Results”). Thus, Liu teaches a method for treating Alzheimer's disease in a patient, the method comprising administering a therapeutically effective amount of extract from rabbit skin inflamed by vaccinia virus to the patient.
With respect to independent claim 4, Liu teaches the APP/PS1 mice treated with NTP showed significantly lower amyloid plaques in both the cortical and hippocampal areas than the control APP/PS1 mice (see p. 8, section (ii) “Chronic NTP treatment reduces Aβ burden in APP/PS1 mice”), thus teaches a method for alleviating or reducing β-amyloid plaque deposition in the brain of a patient suffering from Alzheimer's disease by administering a therapeutically effective amount of extract from rabbit skin inflamed by vaccinia virus to the patient.
With respect to independent claim 5, Liu teaches significant decreases in the area percentage of Iba-1-IR microglia was observed accompanied with reduced Aβ burden in NTP-treated APP/PS1 mice and consistently, the area percentage of GFAP-IR astrocytes also reduced after NTP treatment (see p. 9, section (iii) “Chronic NTP treatment inhibits glial activation in APP/PS1 mice”), thus teaches a method for alleviating or reducing inflammatory response of glial cells in the brain of a patient suffering from Alzheimer's disease, by administering a therapeutically effective amount of extract from rabbit skin inflamed by vaccinia virus to the patient.
With respect to independent claim 7, Liu teaches APP/PS1 control mice had markedly higher levels of IL-1β than NTP-treated APP/PS1 mice (Fig. 3E). After NTP treatment, APP/PS1 mice showed decreased IL-6 level (Fig. 3F). Additionally, the level of TNF-α was lower in NTP-treated group when compared with APP/PS1 mice without NTP treatment (see p. 9, section (iv) “NTP treatment decreases pro-inflammatory cytokines in APP/PS1 mice”). Thus, Liu teaches a method for alleviating or reducing the expression or level of inflammatory factors in the brain of a patient suffering from Alzheimer's disease by administering a therapeutically effective amount of extract from rabbit skin inflamed by vaccinia virus to the patient.
With respect to independent claim 9, Liu teaches “Compared with WT mice, control APP/PS1 mice still show a failure in learning trend, indicating impaired learning ability (P < 0.01, Fig. lB). In contrast, NTP-treated APP/PS1 mice exhibited a comparable learning trend with WT mice” (see p. 8, section (i) “Chronic NTP treatment attenuates cognitive deficits of APP/PS1 mice in the Morris water Maze”). Thus, Liu teaches a method for improving, cognitive functions in a patient suffering from Alzheimer's disease by administering a therapeutically effective amount of extract from rabbit skin inflamed by vaccinia virus to the patient.
With respect to claim 2 directed to the extract alleviating damage to neurological function, as stated supra, Liu teaches NTP treatment attenuates cognitive deficits of APP/PS1 mice (p. 8, section (i)) and teaches NTP treatment reduced the volume of infarcted lesions, brain edema, and the resulting neurological deficits, and enhanced spatial learning (e.g., p. 1, last full para.).
With respect to claim 3, as stated supra, Liu teaches NTP treatment reduces Aβ burden (p. 8, section (ii)), inhibits glial activation (p. 9, section (iii)) and decreases pro-inflammatory cytokines in APP/PS1 mice (p. 9, section (iv)).
With respect to claim 6 and claim 15, as stated supra, Liu teaches significant decreases of Iba-1-IR microglia and GFAP-IR astrocytes after NTP treatment (see p. 9, section (iii)), thus teaches the glial cells being microglia or astrocyte.
With respect to claim 8 and claim 16, as stated supra, Liu teaches the levels of IL-1β, IL-6 and TNF-α are lower in NTP-treated group (see p. 9, section (iv)).
With respect to claim 11, Liu teaches the agent is an injection agent or an oral agent (e.g., p. 2, line 5 from bottom) and exemplifies oral gavage of NTP (p. 6, para 1).
Accordingly, Liu anticipates instant claims.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 10, 12-14 and 17-20 are rejected under 35 U.S.C. 103 as being unpatentable over Liu et al., (WO2020/154941 A1) in view of Lau (WO2020/211009 A1. Cited in IDS 10/01/2024. English translation attached).
Claim 10 is directed to the extract from rabbit skin inflamed by vaccinia virus being Lepalvir.
However, Liu is silent on the extract from rabbit skin inflamed by vaccinia virus being Lepalvir.
Lau teaches use of extract from rabbit skin inflamed by vaccinia virus in treating hematopoietic system damage and teaches the extract from rabbit skin inflamed by vaccinia virus can be lepalvir (e.g., abstract), and teaches this vaccinia virus-inflamed rabbit skin extract injection is commercially available under the trade name Lepalvir, produced by Vishay Pharmaceutical (Rugao) Co., Ltd. (p. 3, the last paragraph above the bullet points).
Therefore, it would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to have substituted Lepalvir for NTP as the extract from rabbit skin inflamed by vaccinia virus as suggested by Lau in the method of Liu with a reasonable expectation of success. Since Lau teaches Lepalvir is commercially available (p. 3, the last paragraph above the bullet points) and has reduced to practice a method of using Lepalvir in treating diseases (e.g., p. 5, section “4. Experimental results”), one of ordinary skill in the art would have had a reason to use Lepalvir as the extract from rabbit skin inflamed by vaccinia virus in order to take its advantage of commercial availability. Furthermore, since Liu’s NTP and Lau’s Lepalvir have the same structure (i.e., both being the extract from rabbit skin inflamed by vaccinia virus with proven functions), these extracts are art-recognized obvious equivalents to each other. Therefore, it would have been obvious for one of ordinary skill in the art to have substituted Lau’s Lepalvir for Liu’s NTP. See MPEP 2144.06.
With respect to claim 12 directed to the patient being a human, Liu teaches NTP may be a new promising drug candidate for patients with AD, and teaches NTP has established safe profiles in humans (e.g., p. 12, last para), and Lau teaches the vaccinia virus-inflamed rabbit skin extract is administered to a human patient (see e.g., p. 1, section “Claims”). Thus, both Liu and Lau suggest a human patient.
Claims 13-14 and 17-20 are directed to the dosage and medicament form of the extract. As stated supra, prior art Lau is used to teach the units of the extract from rabbit skin inflamed by vaccinia virus.
Lau teaches the vaccinia virus-inflamed rabbit skin extract is administered to a patient at a rate of 0.01 U/kg to 5 U/kg (e.g., p. 1, section “Claims”), thus overlaps with or encompasses the range in claims 13, 17 and 18. Lau teaches a method of using the vaccinia virus-inflamed rabbit skin extract in preparing a medicine (i.e., the extract is prepared into a medicament), and the drug contains 0.6 U to 300 U of the vaccinia virus-inflamed rabbit skin extract (e.g., p. 1, section “Claims”), thus overlaps with or encompasses the range in claims 14, 19 and 20.
Therefore, it would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to have chosen the dosage and medicament form of the extract from rabbit skin inflamed by vaccinia virus as suggested by Lau with a reasonable expectation of success. One of ordinary skill in the art would have had a reason to do so since Lau has reduced to practice the dosage and medicament in treating diseases. Furthermore, it is noted that in the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art", a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). It is a routine procedure to optimize component amounts to arrive at an optimal product that is superior for its intended use, since it has been held where the general conditions of a claim are disclosed in the prior art, discovering the optimum or workable ranges involves only routine skill in the art. See M.P.E.P. §2144.05.
Hence, the claimed invention as a whole was prima facie obvious to a person of ordinary skill before the effective filing date of the claimed invention in the absence of evidence to the contrary.
Double Patenting Rejections
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/process/file/efs/guidance/eTD-info-I.jsp.
Claims 1-20 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims of US Patent Nos: 12,090,176 and 12,472,210 in view of Liu et al., (WO2020/154941 A1) and Lau (WO2020/211009 A1. Cited in IDS 10/01/2024. English translation attached). Although the claims at issue are not identical, they are not patentably distinct from each other.
Patented claims in ‘176 recites a method of treating leukopenia induced by anti-cancer therapy in a patient in need thereof, wherein the method comprises administering to the patient a composition comprising a therapeutically effective amount of an extract from rabbit skin inflamed by vaccinia virus (reference claim 1), wherein the composition is administered orally or by injection; wherein the injection is an intramuscular injection or an intravenous injection (reference claim 3, related to instant claim 11), wherein the extract from rabbit skin inflamed by vaccinia virus is administered to the patient in an amount of 0.01 U/kg to 5 U/kg, 0.1 U/kg to 2.5 U/kg, or 0.15 U/kg to 1.15 U/kg; or the composition comprises 0.6 U to 300 U, 6 U to 150 U, or 9 U to 70 U of the extract from rabbit skin inflamed by vaccinia virus (reference claim 4, related to instant claims 13-14 and 17-20), and wherein the patient is human (reference claim 6, related to instant claim 12).
Patented claims in ‘210 recites a method for treating cancer in a human patient in need thereof, the method comprises administering a therapeutically effective amount of a first anticancer agent; wherein the first anticancer agent is an extract from rabbit skin inflamed by vaccinia virus; wherein the therapeutically effective amount of the first anticancer agent is about 1.6 U/kg (reference claim 1, related to instant claim 12, and claims 13, 17 and 18, and makes obvious claims 14, 19 and 20 based on an average of 60 kg body weight of a human patient), wherein the extract from rabbit skin inflamed by vaccinia virus is formulated into an oral formulation or an injection and wherein the injection is an intramuscular injection, intraperitoneal injection, subcutaneous injection, or intravenous injection (reference claims 2-3, related to instant claim 11).
However, cited patent claims are silent on a method for treating Alzheimer’s disease or alleviating β-amyloid plaque deposition, inflammatory response of glial cells or the expression of inflammatory factors in the brain or improving cognitive functions in a patient suffering from Alzheimer’s disease in instant independent claims 1, 4, 5, 7, and 9 or dependent claims 2-3, 6, 8, 15-16, or the extract being Lepalvir in instant claim 10.
Liu teaches a method for alleviation, progression control or treatment of Alzheimer's disease (e.g., p. 2, lines 7-8 from bottom) by administering Neurotropin (NTP), which is a well-known analgesic derived from inflamed rabbit skin inoculated with vaccinia virus with beneficial results (e.g., p. 6, para 1 for administering, p. 1 for describing “NTP” and p. 8, section (9) for “Results”), related to instant claim 1. Liu teaches the APP/PS1 mice treated with NTP showed significantly lower amyloid plaques in both the cortical and hippocampal areas than the control APP/PS1 mice (see p. 8, section (ii)), related to instant claims 3 and 4. Liu teaches significant decreases in the area percentage of Iba-1-IR microglia was observed accompanied with reduced Aβ burden in NTP-treated APP/PS1 mice and consistently, the area percentage of GFAP-IR astrocytes also reduced after NTP treatment (see p. 9, section (iii)), related to instant claims 3, 5, 6 and 15. Liu teaches the levels of IL-1β, IL-6 and TNF-α are lower in NTP-treated group when compared with APP/PS1 mice without NTP treatment (see p. 9, section (iv)), related to instant claims 3, 7, 8 and 16. Liu teaches “Compared with WT mice, control APP/PS1 mice still show a failure in learning trend, indicating impaired learning ability (P < 0.01, Fig. lB). In contrast, NTP-treated APP/PS1 mice exhibited a comparable learning trend with WT mice” (see p. 8, section (i)), related to instant claims 2 and 9.
Lau teaches use of extract from rabbit skin inflamed by vaccinia virus in treating hematopoietic system damage and teaches the extract from rabbit skin inflamed by vaccinia virus can be lepalvir (e.g., abstract), and teaches this vaccinia virus-inflamed rabbit skin extract injection is commercially available under the trade name Lepalvir, produced by Vishay Pharmaceutical (Rugao) Co., Ltd. (p. 3, the last paragraph above the bullet points), related to instant claim 10.
Therefore, it would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to have substituted treating Alzheimer’s disease using the extract from rabbit skin inflamed by vaccinia virus recited in the patent claims as suggested by Liu and to have chosen Lepalvir as suggested by Lau with a reasonable expectation of success. Since Liu has taught using extract from rabbit skin inflamed by vaccinia virus in the instantly claimed methods, and since Lau has reduced to practice a commercially available Lepalvir as the extract, one of ordinary skill in the art would have had a reason to apply the extract in the reference patents to treat the Alzheimer’s disease as suggested by Liu and to choose Lepalvir as the extract as suggested by Lau in order to treat the most prevalent cause of dementia (Liu, p. 1, “Background”) and to take advantage of the commercially available Lepalvir.
Since the instant application claims are obvious over cited patent claims, in view of Liu and Lau, said claims are not patentably distinct.
Provisional Double Patenting Rejections
Claims 1-20 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over co-pending claims 1-16 of US Application No. 18/853,274 in view of Liu et al., (WO2020/154941 A1). Although the claims at issue are not identical, they are not patentably distinct from each other.
Copending claims in ‘274 recites a method of treating Parkinson’s disease in a patient, the method comprising administering a therapeutically effective amount of an extract from rabbit skin inflamed by vaccinia virus to the patient (reference claim 1), wherein the extract alleviates damage to neurological function of the brain (reference claim 2, related to instant claim 2), wherein the extract is Lepalvir (reference claim 8, related to instant claim 10), wherein the extract is formulated into an oral preparation or an injection (reference claim 9, related to instant claim 11), wherein the patient is human (reference claim 10, related to instant claim 12), wherein the extract is administered to the patient in an amount of 0.05 U/kg to 50 U/kg, 0.1 U/kg to 10 U/kg, or 0.5 U/kg to 5 U/kg (reference claims 11, 13-14, related to instant claims 13, 17-18), wherein the extract is prepared into a medicament comprising 3 U to 3000 U, 6 U to 600 U, or 30 U to 300 U of the extract (reference claims 12, 15-16, related to instant claims 14, 19-20).
However, cited copending claims are silent on a method for treating Alzheimer’s disease or alleviating β-amyloid plaque deposition, inflammatory response of glial cells or the expression of inflammatory factors in the brain or improving cognitive functions in a patient suffering from Alzheimer’s disease in instant independent claims 1, 4, 5, 7, and 9 or dependent claims 2-3, 6, 8, 15-16.
Liu teaches a method for alleviation, progression control or treatment of Alzheimer's disease (e.g., p. 2, lines 7-8 from bottom) by administering Neurotropin (NTP), which is a well-known analgesic derived from inflamed rabbit skin inoculated with vaccinia virus with beneficial results (e.g., p. 6, para 1 for administering, p. 1 for describing “NTP” and p. 8, section (9) for “Results”), related to instant claim 1. Liu teaches the APP/PS1 mice treated with NTP showed significantly lower amyloid plaques in both the cortical and hippocampal areas than the control APP/PS1 mice (see p. 8, section (ii)), related to instant claims 3 and 4. Liu teaches significant decreases in the area percentage of Iba-1-IR microglia was observed accompanied with reduced Aβ burden in NTP-treated APP/PS1 mice and consistently, the area percentage of GFAP-IR astrocytes also reduced after NTP treatment (see p. 9, section (iii)), related to instant claims 3, 5, 6 and 15. Liu teaches the levels of IL-1β, IL-6 and TNF-α are lower in NTP-treated group when compared with APP/PS1 mice without NTP treatment (see p. 9, section (iv)), related to instant claims 3, 7, 8 and 16. Liu teaches “Compared with WT mice, control APP/PS1 mice still show a failure in learning trend, indicating impaired learning ability (P < 0.01, Fig. lB). In contrast, NTP-treated APP/PS1 mice exhibited a comparable learning trend with WT mice” (see p. 8, section (i)), related to instant claims 2 and 9.
Therefore, it would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to have substituted treating Alzheimer’s disease using the extract from rabbit skin inflamed by vaccinia virus recited in the copending claims as suggested by Liu with a reasonable expectation of success. Since Liu has taught using extract from rabbit skin inflamed by vaccinia virus in the instantly claimed methods, one of ordinary skill in the art would have had a reason to apply the extract in the reference application to treat the Alzheimer’s disease as suggested by Liu in order to treat the most prevalent cause of dementia (Liu, p. 1, “Background”).
Since the instant application claims are obvious over cited application claims, in view of Liu, said claims are not patentably distinct.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims in the copending application have not in fact been patented.
Conclusion
No claims are allowed.
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/JIANJIAN ZHU/Examiner, Art Unit 1631
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