DETAILED ACTION
This office action is in response to applicant’s filing dated June 28, 2024.
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 .
Status of claims
Claims 1 - 9 are pending in the instant application. Acknowledgment is made of Applicant’s amendments filed June 28, 2024. Acknowledgment is made of Applicant’s addition of a new claims 8 and 9.
Priority
The present application is a 371 of PCT/EP2023/051074, filed January, 18, 2023, and claims the benefits of priority to European patent application EP22305058.4, filed January, 19, 2022.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 06/28/2024 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
Drawings
Acknowledgement is made of the drawings received on June 28, 2024. The drawings are objected to because the image in Figure 1A could not be clearly read due to poor image quality. Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Claim Objections
Claim 7 is objected to because of the following informalities: the claim contains repeated word “dominant” in line 4, as shown herein:
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which it appears to be a typographical error. Furthermore, there is an unneeded capital letter in word “Recessive”, as shown herein:
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. Appropriate correction is required.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 1 – 5 and 8 are rejected under 35 U.S.C. 101 because the claimed invention is directed to non-statutory subject matter. The claim(s) does/do not fall within at least one of the four categories of patent eligible subject matter because the claimed invention is directed to a product of nature without significantly more. The claims recite a composition, representing a plant extract and a compound Geralexin, isolated from said plant extract. The purified compound Geralexin is not markedly different from its naturally occurring counterpart because it has an identical chemical structure and therefore properties. This judicial exception is not integrated into a practical application because claims are directed to the natural phenomena (product of nature) and do not recite any additional elements or steps linking the use of the judicial exception to a particular technological environment, which fails to transform claims into patent-eligible subject matter (see MPEP 2106.04).
Claim Rejections - 35 USC § 112
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.
Claim 7 is 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.
Where applicant acts as his or her own lexicographer to specifically define a term of a claim contrary to its ordinary meaning, the written description must clearly redefine the claim term and set forth the uncommon definition so as to put one reasonably skilled in the art on notice that the applicant intended to so redefine that claim term. Process Control Corp. v. HydReclaim Corp., 190 F.3d 1350, 1357, 52 USPQ2d 1029, 1033 (Fed. Cir. 1999). The claim recites terms “sector RP and regional RP” which is unclear what Applicant means under term “regional RP”, since both terms appears to be referring to the same medical conditions, and the accepted meaning is “sector RP.” The term “regional RP”, is indefinite because the specification does not clearly redefine the term.
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 6, 7 and 9 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 enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
To be enabling, the specification of the patent application 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 (Fd. Cir. 1993). Explaining what is meant by "undue experimentation," the Federal Circuit has stated that:
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 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). As pointed out by the court in /n re Angstadt, 537 F.2d 498 at 504 (CCPA 1976), the key word is "undue", not "experimentation".
The factors that may be considered in determining whether a disclosure would require undue experimentation are set forth In re Wands, 8 USPQ2d 1400 (CAFC 1988) at 1404 wherein, citing Ex parte Forman, 230 USPQ 546 (Bd. Apls. 1986) at 547 the court recited eight factors:
1- the quantity of experimentation necessary,
2- the amount of direction or guidance provided,
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 of the art, and
8- the breadth of the claims.
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:
Nature of the invention and the Breadth of the claims.
The invention is drawn to a method for treating all retinal degenerative diseases with natural compound Geralexin, derived from leaves extract of Uvaria chamae. The breadth of the claims is extensive as it includes variety of diseases not only associated with cone degeneration, but also multisystem disorders with retinal changes as one of possible additional symptoms, and thus requiring a complex treatment approach. Some of those conditions are genetic and uncurable (e.g. Recessive Pseudoxanthoma Elasticum (PXE) or Dominant Stickler syndrome). All of these conditions are claimed to be treatable with the plant-derived acetogenin Geralexin.
The relative skill of those in the art.
The relative skill of those in the art is high, generally that of an M.D. or Ph.D. The artisan using Applicant’s invention would generally be a physician with a M.D. degree and several years of experience. However, given the state of the art as set forth above, the artisan is currently unaware of any one particular anticancer agent that is effective against all cancer cell types.
The predictability or unpredictability of the art and the state of the prior art.
The present claims relate to the mechanism underlying the treatment of the claimed diseases with the compound of the instant invention. Although the discovery of such a mechanism may be an important piece of scientific knowledge, it still needs to be turned into a practical application in the form of a specified actual treatment of the pathological conditions. The factor is outweighed, however, by the unpredictable nature of the art. Ex parte Sudilovsky 21 USPQ2d 1702 (Applicant’s invention concerns pharmaceutical activity. Because there is no evidence of record of analogous activity for similar compounds, the art is relatively unpredictable); In re Wright 27 USPQ2d 1510 (the physiological activity of RNA viruses was sufficiently unpredictable that success in developing specific avian vaccine was uncertain). In the instant case, the art is undeveloped, and there is no current scientific evidence that acetogenins are known to be used in the treatment of retinal degenerative diseases. In the current state of the art, acetogenins are known to exhibit cytotoxic properties, with antiproliferative and antitumor effects, and have been investigated for their therapeutic utility in cancer treatment methods. Moreover, acetogenins been implicated in the neurotoxic effects, and chronic exposure to acetogenins can potentiate neural damage. As illustrative of the state of the art, the examiner cites: Zhang et al (International Immunopharmacology 28 (2015) 997–1002), Jacobo-Herrera et al (Front. Pharmacol. 10:783, (2019)) and N.N.C. Lima et al. (PharmaNutrition 20 (2022) 100295).
With regards to unpredictability, Zhang et al., cited for evidentiary purpose teaches: Annonaceous acetogenins exhibit significant bioactivities of antitumor, immunosuppressive, antimalarial, antifeedant and insecticidal by blocking oxidative pathways in complex I of mitochondria. Angiogenesis, the process of new blood vessels sprouting, is closely associated with tumor formation and a range of non-neoplastic diseases such as age-related macular degeneration, ocular neovascularization, peptic ulcers, rheumatoid arthritis and atherosclerosis. Annonaceous acetogenin (AA) is an antitumor drug with anti-angiogenic activity. However, the effect of AA on ocular neovascular disorders remains unclear. AA092 is a new annonaceous acetogenin mimetic and is a novel analog of AA (page 997, “abstract” and “Introduction”). Experimental data indicate that AA092 has therapeutic potential for angiogenesis-associated diseases such as corneal neovascularization (CNV), however, the molecular mechanism of AA092 to inhibit angiogenesis remains to be investigated (page 1001, left column, 2nd paragraph).
Furthermore, with regards to unpredictability, Jacobo-Herrera et al., cited for evidentiary purposes, teaches: the annonaceous acetogenins (AAs) are secondary metabolites found in the Annonaceae family, which are plants employed in traditional medicine for the treatment of cancer and various other diseases. These polyketides are inhibitors of Complex I in the respiratory chain of tumor cells, a process that is closely related to tumor metabolism, cell death, apoptosis, and autophagy (page 1, “summary”). Presumably, such mechanism suggests that the AAs are “harmless” to normal cells; still, more studies should be performed to assure the selectivity of these molecules However, to date, there is little information regarding the toxicity of AAs or Annona extracts. Preclinical studies reported the LD50 (<5 g/kg) of the aqueous extract, recording that higher dose might damage the kidneys. Also, it was observed that the seed extract of A. squamosa could cause liver damage (page 10, “Toxicity Studies”). However, the preclinical data are not sufficient to obtain a good understanding of the pharmacodynamics and kinetics of AAs, and more acute toxicity and solubility tests are needed to assure safety and the possibility of clinical trials with humans (page 11, left column, 2nd paragraph).
Moreover, with regards to unpredictability, N.N.C. Lima et al., cited for evidentiary purposes, teaches: Acetogenins are compounds found in Annonaceae and present cytotoxic properties, with antiproliferative and antitumor effects. The known antitumor action of acetogenins is triggered by the inhibition of mitochondrial complex I activity, which results in cell apoptosis and prevents the proliferation of neoplastic cells, culminating with antitumorigenesis (page 1, “Introduction”). Studies on the antitumor action of acetogenins point to evidence that these substances have important antiproliferative potential and induce cellular mechanisms associated with apoptotic pathways, as well as metastatic restriction of the tumor through a genotoxic mechanism.
However, acetogenins have been described as potent neurotoxic agents, capable of inducing neurodegeneration. Neurotoxic effects of acetogenins, mediated mainly by their ability to cross the blood-brain barrier, promote energy depletion and malfunction in the tau protein. Chronic exposure to these substances can potentiate neural damage. Some acetogenins are associated with the development of a neurodegenerative disease, as reported in tropical islands in the Caribbean, and are known as atypical Guadeloupean parkinsonism (page 2, left column, 3rd paragraph).
These articles plainly demonstrate that the art of developing and testing therapies to treat all types of retinal degenerative diseases with the compounds of instant claims is unpredictable. More generally, the invention is directed toward medicine and is therefore physiological in nature, and physiological activity is generally considered to be an unpredictable factor. See In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970).
The amount of direction or guidance provided and the presence or absence of working examples.
The instant claims, directed to a method of treating all retinal degenerative diseases comprising administering to the subject in need a compound of formula (I) are extremely broad in contrast with the specification that only provides data, showing therapeutic activity of acetogenin Geralexin on cone-enriched cultures from chicken embryo. Although specification provides general directions or guidance of administration regimen, route or dosage e.g.:
- the composition is a pharmaceutical composition comprising an amount the compound of the present invention. Typically, the compound of the present invention may be combined with pharmaceutically acceptable excipients (page 3, lines 20 – 23);
- typical routes of administration typically include systemic routes, e.g., intraarterial, intraocular, intravenous, intramuscular, subcutaneous, intradermal, and other parental routes of administration (page 8, lines 25 – 28);
- the daily dosage of the products may be varied over a wide range from 0.01 to 1,000 mg per adult per day;
- an effective amount of the drug is ordinarily supplied at a dosage level from 0.0002 mg/kg to about 20 mg/kg of body weight per day (page 9, lines 12 – 20), necessary to treat all of the various disease encompassed by the claims, the directions are very broad and include vast variety of known formulations. Absence of working examples is a critical factor to be considered, especially in a case involving an unpredictable and undeveloped art. See MPEP 2164.
The quantity of experimentation necessary.
Because of the known unpredictability of the art (as discussed supra) and in the absence of experimental evidence commensurate in scope with the claims, the skilled artisan would not accept that the compounds encompassed by formula (I) are capable of treating all diseases encompassed by claims. Genentech Inc. vs. Nova Nordisk states, "[A] patent is not a hunting license. It is not a reward for a search but a compensation for its successful conclusion and ‘patent 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" (42 USPQ 2d 1001, Fed. Circuit 1997). As noted above, the experimentation provided is drawn to the treatment of secondary loss of cones related to retinitis pigmentosa (RP), whereas claims also recite multisystem disorders not only associated with cone degeneration. Determining if the claimed compound would treat any particular claimed disease would require formulation of plant extract or isolated compound into a suitable dosage form and subjecting it to clinical trials or to testing in an assay known to correlate to clinical efficacy of such treatment.
Accordingly, the instant claims do not comply with the enablement requirement of 35 U.S.C. 112(a), since to practice the claimed invention a person of ordinary skill in the art would have to engage in undue experimentation, with no assurance of success.
Conclusion
Claims 1 – 9 are rejected. No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ELENA V VISHNYAKOVA whose telephone number is (571)272-3781. The examiner can normally be reached 7:30am - 5pm ET.
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/E.V.V./ Examiner, Art Unit 1691
/SAVITHA M RAO/ Primary Examiner, Art Unit 1691
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