DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA . In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
Priority
The instant application is a 371 of PCT/EP2022/080162 filed on 10/28/2022 and claims foreign priority to EP21205486.0 filed on 10/29/2021. The certified copy of the foreign priority application filed on 04/26/2024 is acknowledged.
Information Disclosure Statement
The information disclosure statement (IDS) filed on 04/26/2024 is in compliance with the provisions of 37 CFR 1.97. Accordingly, this information disclosure statement is being considered by the examiner.
The information disclosure statement (IDS) filed on 05/29/2026 fails to comply with the provisions of 37 CFR 1.98(a)(4) because it lacks the appropriate size fee assertion. It has been placed in the application file, but the information referred to therein has not been considered as to the merits.
Status of the Claims
The preliminary claim amendments filed on 04/26/2024 is acknowledged. Claims 2, 5, 7-8, 10, 12, and 14 are amended.
Accordingly, claims 1-14 are pending and being examined on the merits herein.
Claim Rejections - 35 USC § 112(b)
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1-14 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 1 and 2 recites “treatment or prevention of pulmonary hypertension; preferably the pulmonary hypertension is secondary pulmonary hypertension; more preferably the pulmonary hypertension is pulmonary hypertension secondary to left heart disease (LHD; WHO group II)”.
The term “preferably” is exemplary language. Therefore, claim 1 is indefinite because there is a question or doubt as to whether the limitations following the “preferably” terms are (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) required features of the claims.
Furthermore, the parenthetical “(LHD; WHO group II)” also renders claim 1 indefinite because it is unclear whether the limitation in the parenthetical was meant to limit the “pulmonary hypertension secondary to left heart disease” limitation, or if the parenthetical limitation is merely exemplary and therefore not required.
Claims 3-14 depend from claim 2, but do not overcome the described indefinite issue.
Claim 5 recites “a microparticle or a nanoparticle, preferably the microparticle or nanoparticle comprises a peptide, a protein, and/or polymer”.
Claim 5 recites the term “preferably”, which is exemplary language. Therefore, these claims are indefinite because there is a question or doubt as to whether the limitations following the “preferably” terms are (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) required features of the claims.
Claim 8 recites “an anchoring agent suitable for targeting of pulmonary blood vessels, preferably for targeting of pulmonary arteries”.
Claim 10 recites “a pulmonary blood vessel; preferably to a structure of a cell of a pulmonary blood vessel or a component of the extracellular matrix of a pulmonary blood vessel”.
Claim 11 recites “elastin, preferably human elastin”.
Claim 13 recites “a linker molecule; preferably via a PEG-linker”.
Claim 14 recites “topical or systemic administration, preferably for intravascular, intravenous, intra-arterial, intracardial, intra-pulmonal and/or nasal administration”.
Claims 8, 10-11, and 13-14 also recite the term “preferably” and is also indefinite for the same reasons indicated above for claim 5.
Claim Rejections - 35 USC § 112(a)
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1-14 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 treatment of pulmonary hypertension, does not reasonably provide enablement for prevention of pulmonary hypertension. 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.
To be enabling, the specification of the patent must teach those skilled in the art how to make and use the full scope of the claimed invention without undue experimentation. In re Wright, 999 F.2d 1557, 1561 (Fed. Cir. 1993). Explaining what is meant by “undue experimentation,” the Federal Circuit has stated:
The test is not merely quantitative, since a considerable amount of experimentation is permissible, if it is merely routine, or if the specification in question provides a reasonable amount of guidance with respect to the direction in which the experimentation should proceed to enable the determination of how to practice a desired embodiment of the claimed invention. PPG v. Guardian, 75 F.3d 1558, 1564 (Fed. Cir. 1996).
The factors that may be considered in determining whether a disclosure would require undue experimentation are set forth by In re Wands, 8 USPQ2d 1400 (CAFC 1988) at 1404 where the court set forth the eight factors to consider when assessing if a disclosure would have required undue experimentation. Citing Ex parte Formal, 230 USPQ 546 (BdApls 1986) at 547 the court recited eight factors:
1) The breadth of the claims,
2) The nature of the invention,
3) The state of the prior art,
4) The level of one of ordinary skill,
5) The level of predictability in the art,
6) The amount of direction provided by the inventor,
7) The existence of working examples, and
8) The quantity of experimentation necessary
These factors are always applied against the background understanding that scope of enablement varies inversely with the degree of unpredictability involved. In re Fisher, 57 CCPA 1099, 1108, 427 F.2d 833, 839, 166 USPQ 18, 24 (1970). Keeping that in mind, the Wands factors are relevant to the instant fact situation for the following reasons:
The nature of the invention, the breadth of the claims, and relative skill level
The invention relates to a pentagalloyl glucose (PGG) and pharmaceutical compositions therefor for use in treatment or prevention of pulmonary hypertension.
The claims are broad in that they encompass the intended use of prevention of pulmonary hypertension.
In the absence of an explicit definition in Applicant’s specification, the claims are given their broadest reasonable interpretation (See MPEP 2111). Institute for International Medical Education (IIME, reference included with PTO-892), defines “prevention” as promoting health, preserving health, and to restore health when it is impaired, and to minimize suffering and distress (see page 16, “Prevention”). IIME further states that “Primary prevention refers to the protection of health by personal and community wide effects, such as preserving good nutritional status, physical fitness, and emotional well-being, immunizing against infectious diseases, and making the environment safe. Secondary prevention can be defined as the measures available to individuals and populations for the early detection and prompt and effective intervention to correct departures from good health. Tertiary prevention consists of the measures available to reduce or eliminate long-term”.
Therefore, in order to give the broadest reasonable interpretation to the claims, “prevention” or "prevent" are thus interpreted to mean that the onset of a condition never occurs and the patient’s health is protected and preserved.
The relative skill of those in the art is high, that of an MD or PHD, someone with experience in the recited conditions/diseases.
The amount of direction or guidance provided and the presence or absence of working examples
Applicant demonstrates in the Examples (pages 28-29) of the specification that targeted delivery of PGG attenuates pulmonary artery stiffening and pulmonary hypertension (PH) in a rat model of PH-LHD (pulmonary hypertension – left heart disease). Applicant demonstrates in FIGS. 8-9 that RVSP and RV hypertrophy were markedly reduced in PGG treated animals and that PGG treated rats showed an increase in pulmonary artery distensibility and pulmonary acceleration time, and a stabilization of tricuspid annular plane systolic excursion (TAPSE). Applicant discloses that PGG treatment improved PA biomechanics and pulmonary hemodynamics even in the face of progressively deteriorating LV function.
However, the instant disclosure does not identify a method that could be used by one of ordinary skill in the art to determine that a subject would have predictably developed pulmonary hypertension without the claimed methods in order to establish that the pulmonary hypertension was prevented.
The described example suggests that the recited PGG composition was effective in treating pulmonary hypertension. However, the example does not demonstrate prevention of the pulmonary hypertension or a predictable method to identify patients who would have developed pulmonary hypertension.
The state and predictability of the art
There are no art recognized methods that could be used to establish that pulmonary hypertension was prevented using therapeutic treatment or to identify patients who would predictably develop pulmonary hypertension in order to predictably identify that prevention was achieved using therapeutic approaches. Rather, the art indicates that identifying patients who would develop pulmonary hypertension was not predictable.
For example, Hoeper (in PTO-892) discloses that there are controversies and debates as to the criteria and definitions of pulmonary hypertension (see section “Definitions, Limitations, Uncertainties, and Controversies” section, pages D43-D46). Furthermore, Hoeper discloses that early diagnosis of pulmonary arterial hypertension remains difficult, and screening programs in asymptomatic patients are feasible only in high-risk populations (Abstract). Hoeper discloses that despite increasing awareness, there is often considerable delay between onset of symptoms and diagnosis of idiopathic pulmonary arterial hypertension (IPAH) and 21% of patients had symptoms greater than 2 years before diagnosis (second paragraph left column page D48).
The teachings of Hoeper demonstrate that the early diagnosis of pulmonary arterial hypertension remains difficult to diagnose for the general population, and further discloses that even in high-risk populations, screening is still required to determine if pulmonary hypertension onset has occurred in asymptotic patients, further suggesting that the onset of pulmonary hypertension is not predictable. Therefore, these teachings demonstrate that there is no method available to predictably determine that pulmonary hypertension would have developed in order to establish that it was prevented.
The quantity of experimentation necessary
Because of the known unpredictability of the art, and in the absence of a predictable method to identify patients who would develop a pulmonary hypertension without treatment, one of ordinary skilled in the art would not be able to predictably identify that pulmonary hypertension was prevented using the claimed agents. Furthermore, the quantity of experimentation would be undue because a method to identify a patient who would predictably get this condition in order to establish that the claimed method results in prevention does not exist.
Accordingly, the instant claims do not comply with the enablement requirement of §112, since to practice the invention claimed in the patent a person of ordinary skill in the art would have to engage in undue experimentation, with no assurance of success.
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.
Claim(s) 1-5 and 7-14 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Parasaram et al. (Respiratory Research, published 09/18/2021 in PTO-892).
Parasaram discloses the targeted delivery of pentagalloyl glucose (PGG) to inhibit matrix metalloproteinase activity and preserve elastin in emphysematous lungs (Abstract).
Parasaram performed experiments by creating mice model for emphysema by elastase inhalation challenge (Abstract).
Parasaram discloses that albumin nanoparticles (NPs) loaded with PGG, conjugated to elastin antibody, and were administered via inhalation to target degraded elastin in the lungs of the mice (Abstract and second paragraph left column page 3). Parasaram discloses that mice treated with PGG nanoparticles showed a significant suppression of MMP-12 activity measured in the lungs and had elastin preservation in the lungs (Abstract). The PGG NPs of Parasaram would necessarily be a pharmaceutical composition since it was administered to mice by inhalation.
Parasaram discloses that the elastin antibody was conjugated to the PGG-loaded albumin nanoparticle via a PEG linker (section “Tagging NPs with elastin antibody” page 1 in the attached Supplementary Information in PTO-892)
While Parasaram does not disclose their PGG NPs for use in treatment of pulmonary hypertension, the PGG NPs of Parasaram would be capable of performing this intended use as the PGG NPs of Parasaram are administered and targeted to the lungs. Furthermore, Parasaram discloses that PGG has been shown to preserve elastin in vascular tissues from elastolytic damage and aid in elastin deposition by vascular smooth muscle cells and pulmonary fibroblasts (second paragraph left column page 2).
MPEP 2111.02 II states that “To satisfy an intended use limitation which is limiting, a prior art structure which is capable of performing the intended use as recited in the preamble meets the claim. See, e.g., In re Schreiber, 128 F.3d 1473, 1477, 44 USPQ2d 1429, 1431 (Fed. Cir. 1997) (anticipation rejection affirmed based on Board’s factual finding that the reference dispenser (a spout disclosed as useful for purposes such as dispensing oil from an oil can) would be capable of dispensing popcorn in the manner set forth in appellant’s claim 1 (a dispensing top for dispensing popcorn in a specified manner)) and cases cited therein.”
Therefore, instant claims 1-5 and 7-14 are anticipated.
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.
Claim(s) 2-3 and 5-6 are rejected under 35 U.S.C. 103 as being unpatentable over Parasaram et al. (Respiratory Research, published 09/18/2021 in PTO-892) in view of Elzoghby et al. (Journal of Controlled Release, 2012 in PTO-892).
The teachings of Parasaram are as described above.
While Parasaram teaches PGG-loaded albumin nanoparticles (NPs) conjugated to an elastin antibody, Parasaram does not teach that their NPs are biodegradable.
Elzoghby discloses the use of albumin-based nanoparticles as potential controlled release drug delivery systems (Abstract).
Elzoghby discloses that albumin is a versatile protein carrier for drug delivery and has been shown to be non-toxic, non-immunogenic, biocompatible, and biodegradable (Abstract). Therefore, Elzoghby discloses that albumin is an ideal material to fabricate nanoparticles for drug delivery (Abstract). Elzoghby reviews several albumin-based nanoparticles and conclude these albumin nanoparticles have high binding capacity of various drugs, are well tolerated without any serious effects, and have biodegradability / biocompatibility (Abstract and Conclusion section first paragraph page 179).
Therefore, one of ordinary skill in the art before the effective filing date of the claimed invention would have a reasonable expectation that the PGG-loaded albumin nanoparticles of Parasaram would be biodegradable based on the teachings of Elzoghby, which discloses that albumin-based nanoparticles have been shown to be non-toxic, non-immunogenic, biocompatible, and biodegradable.
Conclusion
No claim is found allowable.
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/D.H.C./Examiner, Art Unit 1693
/SCARLETT Y GOON/Supervisory Patent Examiner
Art Unit 1693
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