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/Restrictions
Applicant’s election without traverse of Group I (i.e., claims 16-25 and 31-35 drawn to a cysteine inhibitor of natural origin comprising at least one of cystatin polypeptide, a plurality of l-amino acid oligopeptides, or combinations thereof) in the replies filed on July 8, 2024; December 23, 2024; and April 12, 2025, are acknowledged. Additionally, Applicant’s election without traverse of Species A (i.e., a single and specific cysteine peptidase inhibitor as cystatin derived from Knotweed); and Species B (i.e., a single and specific use as prevention and treatment of periodontitis) in the replies filed on July 8, 2024; December 23, 2024; April 12, 2025; and the telephonic election (please see attached interview summary), are acknowledged.
Please note that the source of the cystatin polypeptide of Species A is hereby removed. As such, Species A is limited to any full length cystatin polypeptide.
Status of Claims
Claims 1-15 were originally filed on August 14, 2021.
The amendment received on November 3, 2022, canceled claims 1-15; and added new claims 16-30. The amendment received on July 8, 2024, canceled claim 20; amended claims 18-19 and 23-25; and added new claims 31-37. The amendment received on December 23, 2024, amended 16-17, 19-20, 22, and 24; and added new claims 31-35. The amendment received on April 12, 2025, canceled claims 16-19 and 21-37; and added new claims 38-57.
Claims 38-57 are currently pending and claims 38, 40-42, 44-48, 51-52, 54, and 56-57 are under consideration as claims 39, 43, 49-50, 53, and 55 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Election was made without traverse in the replies filed on July 8, 2024; December 23, 2024; April 12, 2025; and the telephonic election (please see attached interview summary).
Priority
The present application claims status as a 371 (National Stage) of PCT/PL2020/000018 filed February 15, 2020, and claims priority under 119(a)-(d) to Polish Application Nos. P.428931 filed on February 15, 2019, and P.431519 filed October 18, 2019.
Receipt is acknowledged of papers submitted under 35 U.S.C. 119(a)-(d) for Polish Application Nos. P.428931 and P.431519, which papers have been placed of record in the file. Please note that the Polish applications are in a foreign language and therefore cannot be verified.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on August 14, 2021 is being considered by the examiner. Please note that the FP and NPL documents have been crossed out and not considered as a copy of each document has not been provided as required pursuant under 37 CFR 1.98.
Claim Interpretation
For purposes of applying prior art, the claim scope has been interpreted as set forth below per the guidance set forth at MPEP § 2111. If Applicant disputes any interpretation set forth below, Applicant is invited to unambiguously identify any alleged misinterpretations or specialized definitions in the subsequent response to the instant action. Applicant is advised that a specialized definition should be properly supported and specifically identified (see, e.g., MPEP § 2111.01(IV), describing how Applicant may act as their own lexicographer).
For claim 38, with respect to “cystatin polypeptide”, it is noted that the scope of the cysteine peptidase inhibitor encompasses any naturally occurring full length cystatin polypeptide including cystatin proteins from animals, plants and microorganisms (See Shamsi et al., Intl. J. Biol. Macromol. 102:674-693 (2017) at abstract). Shamsi et al. teaches that cystatins are virtually the most widely represented class of cysteine proteinase inhibitors, ubiquitously distributed in plants and animals, and devoted to regulating degradation of both intracellular and extracellular proteins (See Shamsi article, pg. 678, col. 1, last paragraph). The cystatin superfamily encompasses proteins that contain multiple cystatin-like sequences (See Shamsi article, pg. 678, col. 2, 1st paragraph). The proteins which collectively form the cystatin superfamily have been subdivided into three families; namely, stefins (Family 1), the cystatins (Family 2) and the kininogens (Family 3), but recently determined protein sequences indicate that the classification could be extended to include additional families such as phytocystatins (Family 4) that include all cystatin proteinase inhibitors isolated from plant (See Shamsi article, pg. 678, col. 2, 1st paragraph). As such, the scope of the claimed cystatin polypeptide encompasses any cystatin from one of the four cystatin families. Given the pre-existing knowledge regarding the structures of each family of cystatins, e.g., phytocystatins tend to be small proteins with a molecular mass of 12-16 kDa and contain a highly conserved region of the G58 residue, the QVVAG motif and a PW motif (See Shamsi article, pg. 682, col. 1, last paragraph), an ordinary skilled artisan would have put one in possession of the claimed subgenus of cystatin polypeptides that exhibit the function of inhibiting a cysteine peptidase. Thus, an ordinary skilled artisan would conclude that the applicant was in possession of the claimed subgenus of cystatin polypeptides at the time the application was filed. NOTE: examination/consideration is limited to the elected cystatin polypeptide. Consideration of a plurality of L-amino acid oligopeptides has not been made yet.
Claim Objections
Claims 40-42, 44-45, 47-48, 52, 54, and 56-57 are objected to because of the following informalities: each claim recites, “wherein it is…” It is respectfully requested that each claim replace “it” with “the cysteine peptidase inhibitor”. Appropriate correction is required.
Claims 45 and 52 are objected to because of the following informalities: each claim recites, “Fallopia japonica”. It is respectfully requested that the claims recite, “Fallopia japonica” in order to be grammatically correct. Appropriate correction is required.
Claim 46 is objected to because of the following informalities: each claim recites, “wherein, and is…” It is respectfully requested that claim 46 recites, “wherein the cysteine peptidase inhibitor is….” Appropriate correction is required.
Claims 46 and 54 are objected to because of the following informalities: each claim recites, “…and other glycols free environment.” It is respectfully requested that the claims recite, “…and other glycol-free environments” in order to be grammatically correct. Appropriate correction is required.
Claim Rejections - 35 USC § 112
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 41, 47, and 56 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 treatment of periodontitis by using a cysteine peptidase inhibitor of natural origin comprising a cystatin polypeptide, does not reasonably provide enablement for the prevention of periodontitis by using a cysteine peptidase inhibitor of natural origin comprising a cystatin polypeptide. 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.
As stated in MPEP §2164.01(a), “there are many factors to consider when determining whether there is sufficient evidence to support a determination that a disclosure does not satisfy the enablement requirement and whether any experimentation is ‘undue’.” These factors include, but are not limited to:
1. The breadth of the claims;
2. The nature of the invention;
3. The state of the prior art;
4. The level of skill in the art;
5. The level of predictability in the art;
6. The amount of direction provided by the inventor;
7. The presence or absence of working examples;
8. The quantity of experimentation necessary needed to make or use the invention based on the disclosure.
See In re Wands USPQ 2d 1400 (CAFC 1988).
The eight In re Wands factors are applied to Claims 41, 47, and 56 as follows:
The Breadth of the Claims and The Nature of the Invention
Although addressing that a cysteine peptidase inhibitor of natural origin comprising a cystatin polypeptide can be used in prevention and treatment of periodontitis in human and veterinary medicine in claims 41, 47, and 56, Applicants do not provide any evidence in the specification that a cysteine peptidase inhibitor of natural origin comprising a cystatin polypeptide can prevent periodontitis. It is noted that the instant specification does not define what constitutes prevention of periodontitis in human and veterinary medicine. As such, the plain and ordinary meaning of the term applies. Merriam Webster defines “prevent” as to keep from happening or existing (See Merriam Webster, “Prevent”, Merriam Webster, available online at https://www.merriam-webster.com/dictionary/prevent, 9 pages (accessed on June 26, 2025)). As such, prevention encompasses 100% prevention. Therefore, the scope of claims 41, 47, and 56 encompass where a cysteine peptidase inhibitor of natural origin comprising a cystatin polypeptide 100% prevents periodontitis. Accordingly, claims 41, 47, and 56 are unduly broad with respect to preventing periodontitis.
The State of the Prior Art
It is noted that there is currently no prior art that demonstrates that a cysteine peptidase inhibitor of natural origin comprising a cystatin polypeptide 100% prevents periodontitis.
The Level of Skill in the Art
Practitioners in this art (medical clinicians, pharmacists, doctors and/or pharmaceutical chemists) would presumably be highly skilled in the art for prevention of periodontitis by using a cysteine peptidase inhibitor of natural origin comprising a cystatin polypeptide.
The Level of Predictability in the Art
The instant claimed invention is highly unpredictable. If one skilled in the art cannot readily anticipate the effect of a change within the subject matter to which that claimed invention pertains (i.e., preventing periodontitis by using a cysteine peptidase inhibitor of natural origin comprising a cystatin polypeptide), then there is a lack of predictability in the art. Moreover, it is noted that the pharmaceutical art is unpredictable, requiring each embodiment to be individually assessed for physiological activity. The court has indicated that the more unpredictable an area is, the more specific enablement is necessary in order to satisfy the statute. (See In re Fisher, 427 F.2d 833, 166 USPQ 18 (CCPA 1970)). This is because it is not obvious from the disclosure of one species, what other species will work.
In the instant case, Applicants do not demonstrate that a cysteine peptidase inhibitor of natural origin comprising a cystatin polypeptide can be used to prevent periodontitis in human and veterinary medicine. Rather, Applicants demonstrate that a cystatin isolated from knotweed (Table 1), low molecular weight inhibitors without identifying the structure and/or sequence of such low molecular weight inhibitors from knotweed and egg protein (Tables 2-3), and cystatin from egg white (Table 6) reduced cysteine gingipain activity thereby suggesting treatment of periodontitis since gingipaines are proteolytic enzymes in P. gingivitalis (See instant specification, pg. 4, 5th paragraph; pg. 22, 1st paragraph; Tables 1-3 and 6). Applicants also demonstrate in Example 1 that cystatin from egg white when rubbed on the gums of dogs resulted in reduced pathogenic cysteine gingipain activity (See instant specification, Example 1; Table 9). Similarly, in vitro experiments in Example 2 demonstrate that cystatin from egg white reduced gingipain activity in extracted gingival pocket fluid from dogs (See instant specification, Example 2; Table 10). Examples 3-4 demonstrate that cystatin from egg white or egg protein reduced cysteine gingipain in humans and a dog (See instant specification, Examples 3-4; Table 11). It is noted that the cystatin from knotweed, egg protein or egg white reduced gingipain activity where the highest % of inhibition is about 97% (See Table 10). As such, Applicants appear to rely on the assumption that by providing evidence that cystatin from knotweed, egg protein or egg white is effective in treating periodontitis by reducing gingipain activity would exhibit similar intended results for the prevention of periodontitis. However, such an assumption cannot be made because there is no evidence of 100% inhibition of activity. Additionally, since the Specification fails to demonstrate any data or evidence that the cystatin polypeptide prevents periodontitis, there would be no way of determining without undue experimentation whether the cystatin polypeptide exhibits such a desired result. Without more experimentation demonstrating the efficacy of a cystatin polypeptide derived from a natural origin, the level of unpredictability remains high. Therefore, it is unpredictable that the claimed cystatin polypeptides will prevent periodontitis in human and veterinary medicine.
The Amount of Direction Provided by the Inventor,
The Presence or Absence of Working Examples, and
The Quantity of Experimentation Necessary
The specification does not enable any person skilled in the art to which it pertains (i.e. preventing periodontitis by using a cysteine peptidase inhibitor of natural origin comprising a cystatin polypeptide) to make and/or use the invention commensurate in scope with the claims. There is a lack of adequate guidance from the specification or prior art with regard to the actual prevention of periodontitis by using a cysteine peptidase inhibitor of natural origin comprising a cystatin polypeptide. Applicants fail to provide the guidance and information required to ascertain where the claimed cystatin polypeptides will be effective against preventing periodontitis without resorting to undue experimentation. Applicant's limited disclosure is noted but is not sufficient to justify claiming prevention of periodontitis.
Absent a reasonable a priori expectation of success for using a cystatin polypeptide of natural origin to prevent periodontitis, one skilled in the art would have to extensively test ginipain activity levels in vitro and in vivo. Since each prospective embodiment, and indeed future embodiments as the art progresses, would have to be empirically tested, and those which initially failed tested further, an undue amount of experimentation would be required to practice the invention as it is claimed in its current scope, because the specification provides inadequate guidance to do otherwise.
As discussed in “The Level of Predictability in the Art” section supra, the amount of direction or guidance presented in the specification is limited to treatment of periodontitis. The Specification discloses several examples where a cystatin polypeptide from knotweed, egg protein or egg white reduced gingipain activity thereby suggestive of periodontitis treatment (See Tables 1-3, 6, and 9-11; Examples 1-4). In examples 1-4, the human or dog subjects already suffered from periodontitis, and the efficacy of the cystatin polypeptide from egg protein or egg white evaluated on gingipain activity levels. The data indicates that the cystatin polypeptide reduced gingipain activity levels. However, as noted in “Breadth of the Claims and Nature of the Invention" Section, prevention encompasses 100% prevention. As such, the experiments discussed in the specification may not be indicative of valid results (i.e., 100% prevention of periodontitis). It is further noted that Applicants provide no data, examples, figures, etc. demonstrating that the claimed cystatin polypeptide is capable of preventing periodontitis. In the absence of such information, a person of ordinary skill in the art would reasonably require an undue quantity of experimentation.
Conclusion of 35 U.S.C. 112(a) (Enablement) Analysis
MPEP §2164.01(a), 4th paragraph, provides that, “A conclusion of lack of enablement means that, based on the evidence regarding each of the above factors, the specification, at the time the application was filed, would not have taught one skilled in the art how to make and/or use the full scope of the claimed invention without undue experimentation. In re Wright, 999 F.2d 1157, 1562; 27 USPQ2d 1510, 1513 (Fed. Cir. 1993).
Genentech Inc. v. Novo Nordisk A/S, 42 USPQ2d 1001, 1005 (CA FC), states 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,” citing Brenner v. Manson, 383 U.S. 519, 536 (1966) (stating, in the context of the utility requirement, that “a patent is not a hunting license. It is not a reward for search, but compensation for its successful conclusion”). The Genentech decision continued, “tossing out the mere germ of an idea does not constitute enabling disclosure. While every aspect of a generic claim certainly need not have been carried out by an inventor, or exemplified in the specification, reasonable detail must be provided in order to enable members of the public to understand and carry out the invention.” Id. at p. 1005.
After applying the Wands factors and analysis to Claims 41, 47, and 56, in view of the applicant’s entire disclosure, and considering the In re Wright, In re Fisher and Genentech decisions discussed above, it is concluded that the practice of the invention as claimed in Claims 41, 47, and 56 would not be enabled by the written disclosure excluding that of treating periodontitis in human and veterinary medicine by using a cysteine peptidase inhibitor of natural origin comprising a cystatin polypeptide. Therefore, Claims 41, 47, and 56, are rejected under 35 U.S.C. §112(a) for failing to disclose sufficient information to enable a person of skill in the art to prevent periodontitis in human and veterinary medicine by using a cysteine peptidase inhibitor of natural origin comprising a cystatin polypeptide.
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 42, 45, and 52 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 42, 45 and 52 are directed to where the inhibitor is obtained from natural raw materials including at least one of knotweed, knotweed species Fallopia japonica, Houtt or combinations thereof. However, it is unclear if Houtt is referring to the F. japonica knotweed species (See USDA, “Japanese Knotweed,” USDA, Natl. Invasive Species Information Center, available online at https://www.invasivespeciesinfo.gov/terrestrial/plants/japanese-knotweed, 5 pages (accessed on 6/27/25) at pg. 1: teaching F. japonica (Houtt.)), or another plant species such as Myristica fragrans (Houtt.), which is an aromatic evergreen tree and is the source of mace (aril) and nutmeg (seed) (See Tuan Ha et al., Arch. Pharm. Res. 43:1067-1092 (2020) at abstract). Houtt appears to refer to the author who first described the species and not a natural material itself. As such, the scope of claims 45 and 52 is further unclear because Houtt is not a natural raw material. Therefore, an ordinary skilled artisan would be unable to ascertain the metes and bounds of the presently claimed invention with respect to if Houtt is referring to a natural raw material/source, if it is associated with F. japonica, or if it is associated with another plant identified by Houtt.
Please note that the Examiner is interpreting the scope of these claims such that Houtt is associated with F. japonica, i.e., F. japonica (Houtt.), in order to advance prosecution.
Claim 48 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. Claim 48 recites the limitation "the form" in line 1. There is insufficient antecedent basis for this limitation in the claim.
Please note that the Examiner is interpreting the scope of claim 48 such that the claim recites “a form” in order to advance prosecution.
Claim 48 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. Claim 48 recites where the cysteine peptidase inhibitor is formulated in the “form” of at least one of an aqueous aerosol, a propylene glycol, a plant glycerol aerosol or combinations thereof…. However, it is unclear how the inhibitor is in the form of a propylene glycol. A “form” implies the inhibitor is a specific form such as a liquid, aerosol, emulsion, etc. Propylene glycol is a solvent/carrier that the inhibitor can be combined with and/or mixed with, but is not a specific “form”. Therefore, an ordinary skilled artisan would be unable to ascertain the metes and bounds of the presently claimed invention with respect to how the inhibitor is in the form of propylene glycol.
Please note the Examiner is interpreting the scope of claim 48 such that the inhibitor is formulated such that the inhibitor is combined with water, propylene glycol, and/or a plant glycerol, and in the form of an aerosol in order to advance prosecution.
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 38, 40-42, 44-48, 51-52, 54, and 56-57 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception (i.e., a natural product) without significantly more. Claim 38 recites a cysteine peptidase inhibitor of natural origin comprising at least one of cystatin polypeptide, a plurality of L-amino acid oligopeptides or combinations thereof. Claim 40 is directed to where the cysteine peptidase inhibitor is in the form of a salt-free aqueous solution. Claims 41, 47, and 56 are directed to where the cysteine peptidase inhibitor is useful in prevention and treatment of periodontitis in humans and veterinary medicine. Claim 42 is directed to where the cysteine peptidase inhibitor is obtained from natural raw materials comprises at least one of knotweed, knotweed species Fallopia japonica, Houtt, mistletoe, soybean, pineapple, rice, potatoes, other substances of natural plant origin or combinations thereof. Claim 44 is directed to where the cysteine peptidase inhibitor is a therapeutically and/or prophylactically active substance. Claims 45 and 52 are directed to where the cysteine peptidase inhibitor is obtained from at least one of knotweed, knotweed species Fallopia japonica, Houtt, and combinations thereof. Claims 46 and 54 are directed to where the cysteine peptidase inhibitor is stable in glycerol and other glycol-free environments. Claim 48 is directed to where the cysteine peptidase inhibitor is formulated in the form of at least one of an aqueous aerosol, a propylene glycol, a plant glycerol aerosol, or combinations thereof; for administration to any one or more of the oral cavity, sinuses, upper and lower respiratory tract. Claim 51 is directed to where the cysteine peptidase inhibitor is a cystatin. Claim 57 is directed to where the cysteine peptidase inhibitor is formulated for administration to any one or more of the oral cavity, sinuses, upper and lower respiratory tract.
Claim 38 expressly recites that the cysteine peptidase inhibitor is of natural origin. As such, the claimed cystatin polypeptide or a plurality of L-amino acid oligopeptides as recited in instant claims 38 and 51 are of natural origin. It is noted that there is no indication that the cystatin polypeptide or plurality of L-amino acid oligopeptides have been modified in a manner to render it markedly different than its naturally occurring counterpart. Claims 42, 45, and 52 further limit the natural origin of the cystatin polypeptide or plurality of L-amino acid oligopeptides. Moreover, the instant specification refers to EP 2511288 as disclosing a method for isolating cystatin from natural, human-friendly raw materials (See instant specification, pg. 14, 3rd paragraph), which method was used to isolate several amino acid peptides from knotweed as discussed in Example 5 (See instant specification, pg. 42, last paragraph). The instant specification also states that it turned out that cystatin separated from the new, low-molecular cysteine inhibitors of the peptidases of the invention, isolated from the knotweed protein mass, especially the Fallopia japonica, Houtt species, is incomparably more durable than cystatin isolated in the same way from egg protein and does not require glycerin stabilization (See instant specification, pg. 17, 1st paragraph). The low molecular weight cysteine peptidase inhibitors of the invention are in fact an unidentified by-product of the process of extracting cystatin from egg protein and from plant materials such as knotweed, Houtt, mistletoe, etc. (See instant specification, pg. 17, 2nd paragraph). Furthermore, natural plant cystatins, i.e., phytocystatins, are known in a number of plants including barley, chestnut, maize, wheat, potato, soybean and tomato (See Benchabane et al., Biochimie 92:1657-1666 (2010) at Table 1). Therefore, the claimed cystatin polypeptide and/or plurality of L-amino acid oligopeptides are naturally occurring given that they are not markedly different from their naturally occurring counterparts because they convey the same genetic information.
Regarding claims 40 and 48, it is noted that the natural cystatin polypeptide and/or natural plurality of L-amino acid oligopeptides being in the form of a salt-free aqueous solution or an aqueous aerosol does not impart a markedly different structure to either the natural polypeptide and/or oligopeptides or water. Water is also naturally occurring as the aqueous solution does not contain any components that render it markedly different than natural water. Plus, there is no indication that the combination of the natural polypeptide and/or oligopeptides and water impart a structural and/or functional modification when compared to their naturally occurring counterparts. Furthermore, being in an aerosol form, e.g., nano- or microparticle size, without evidence to the contrary, does not impart a structural of functional modification to the claimed natural cystatin polypeptide and/or plurality of natural L-amino acid oligopeptides. Therefore, the natural cystatin polypeptide and/or natural plurality of L-amino acid oligopeptides being in the form of a salt-free aqueous solution encompass naturally occurring components because each component is not markedly different from their naturally occurring counterparts.
These judicial exceptions are not integrated into a practical application even though claim 38 recites that the cystatin polypeptide and/or a plurality of L-amino acid oligopeptides function as a cysteine peptidase inhibitor; claims 41, 47, and 56 recite that the cysteine peptidase inhibitor is useful in prevention and treatment of periodontitis, in humans and veterinary medicine; claim 44 recites that the cysteine peptidase inhibitor is a therapeutically and/or prophylactically active substance; claims 46 and 54 are directed to where the cysteine peptidase inhibitor is stable in glycerol and other glycol-free environments thereby constituting functional properties of the inhibitor; and claim 48 recites, in part, that the cysteine peptidase inhibitor is formulated in a form for administration to any one or more of the oral cavity, sinuses, upper and lower respiratory tract, each function/use constitutes a practical application. However, such recitations do not add a meaningful limitation as they merely recite an inherent function and/or intended use of the naturally occurring cystatin polypeptide and/or plurality of L-amino acid oligopeptides and are nothing more than an attempt to generally link the products of nature to a particular technological environment.
The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the structure of the claimed cystatin polypeptide and/or plurality of L-amino acid oligopeptides do not require a modification that is significantly more than the naturally occurring cystatin polypeptide and/or plurality of L-amino acid oligopeptides in order to result in a markedly different cystatin polypeptide and/or plurality of L-amino acid oligopeptides. For example,
The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the structure of the claimed partial peptide does not require a modification that is significantly more than the naturally occurring partial peptide in order to result in a markedly different partial peptide. For example, a fusion protein or conjugated protein as recited in claim 1 constitutes patent eligible subject matter because the partial peptide is fused to a heterologous peptide or protein or conjugated to a non-proteinaceous moiety. Thus, claims 38, 40-42, 44-48, 51-52, 54, and 56-57 encompass patent ineligible subject matter.
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 38, 41-42, 44, 46-47, 51, 54, and 56-57 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Blankenvoorde et al., Biol. Chem. 379:1371-1375 (1998), alone or as evidenced by Cloning et al., J. Biol. Chem. 265:15832-15837 (1990), and Bostanci et al., FEMS Microbiol. Lett. 333:1-9 (2012).
For claims 38, 42 and 51, with respect to a cysteine peptidase inhibitor of natural origin comprising a cystatin polypeptide as recited in instant claims 35 and 51; and with respect to where the inhibitor is obtained from natural raw materials such as rice as recited in instant claim 42:
Blankenvoorde et al. discloses that cystatins exhibit antiviral and antibacterial activity due to the inhibition of essential cysteine proteinases (See Blankenvoorde article, pg. 1371, col. 2, 2nd paragraph). Examples of these cysteine proteinase inhibitors include cystatin C, egg white cystatin, and oryzacystatins display antiviral activity against poliovirus (See Blankenvoorde article, pg. 1371, col. 2, 2nd paragraph). As evidenced by Cloning et al., oryzacystatin is a proteinaceous cysteine proteinase inhibitor (cystatin) in rice seeds and is the first well defined cystatin of plant origin (See Cloning article, abstract). As such, Blankenvoorde et al. discloses oryzacystatin as a cystatin polypeptide that functions as a cysteine peptidase inhibitor of natural origin derived from rice as recited in instant claims 38, 42, and 51.
Although Blankenvoorde et al. expressly discloses that the oryzacystatin exhibits the function of cysteine peptidase inhibition, it is unnecessary for Blankenvoorde to disclose this function. The functional property (i.e., exhibiting cysteine peptidase inhibition) of the cystatin as claimed and the known cystatin are inherently the same. The discovery of a previously unappreciated property of a prior art composition, or a scientific explanation for the prior art’s functioning, does not render the old composition patentably new to the discoverer. Atlas Powder Co. v. Ireco Inc., 190 F.3d 1342, 1347, 51 USPQ2d 1943, 1947 (Fed. Cir. 1999). Thus, the claiming of a new functional property (i.e., exhibiting cysteine peptidase inhibition) which is inherently present in the prior art does not necessarily make the claim patentable. In re Best, 562 F.2d 1252, 1254, 195 USPQ 430, 4333 (CCPA 1977). Therefore, the disclosure of Blankenvoorde et al. satisfies the claim limitations as recited in instant claims 38, 42 and 51.
For claims 41, 47, and 56, with respect to where the inhibitor is useful in treatment of periodontitis in human and veterinary medicine:
Blankenvoorde et al. discloses that chicken cystatin and salivary cystatin S both inhibit the growth of the oral pathogen P. gingivalis (See Blankenvoorde article, pg. 1371, col. 2, 3rd paragraph). Blankenvoorde et al. also found several cystatin S fragments such as cystatin S:1-14, cystatin S:61-73, and cystatin S:108-121 exhibit P. gingivalis growth, albeit, not as effective as the full length cystatin S protein (See Blankenvoorde article, pg. 1372, col. 2, 2nd paragraph; Table 3). As evidenced by Bostanci et al., P. gingivalis is a Gram-negative oral anaerobe that is involved in the pathogenesis of periodontitis (See Bostanci article, abstract). As such, the chicken cystatin and cystatin S constitute claimed cystatin polypeptides that are useful in treatment of periodontitis.
Additionally and/or alternatively, although Blankenvoorde et al. demonstrates that a cystatin polypeptide is useful in treatment of periodontitis, it is unnecessary for Blankenvoorde to disclose this intended use because an intended use of the cystatin polypeptide (i.e., useful in treatment of periodontitis in human and veterinary medicine) does not state a condition that is material to patentability or provide a structural limitation that would further limit the claimed cystatin polypeptide. The court has found that the determination of whether clauses such as “wherein” and “whereby" is a limitation in a claim is dependent on the specific facts of the case. If the “wherein" or “whereby” clause limits a process claim where the clause gives meaning and purpose to the manipulative steps, it should be given patentable weight. However, the court also found (quoting Minton v. Nat’l Ass’n of Securities Dealers, Inc., 336 F.3d 1373, 1381, 67 USPQ2d 1614, 1620 (Fed. Cir. 2003)) that a “‘whereby clause in a method claim is not given weight when it simply expresses the intended result of a process step positively recited.’” In the instant case, the intended use of the cystatin polypeptide (i.e., useful in treatment of periodontitis in human and veterinary medicine) gives little meaning and purpose to the structure of the claimed peptide. Therefore, claims 41, 47, and 56 recite an intended use that does not render material to patentability. Thus, the disclosure of Blankenvoorde et al. satisfies the claim limitations as recited in instant claims 41, 47, and 56.
For claim 44, with respect to where the inhibitor is a therapeutically active substance:
As discussed supra for claims 38, 41-42, 47, 51, and 56, Blankenvoorde et al. demonstrates that chicken cystatin, salivary cystatin S, and specific cystatin S fragments inhibit P. gingivalis growth, which would treat periodontitis. As such, these identified cystatins exhibit a therapeutic effect thereby constituting a therapeutically active substance.
Additionally and/or alternatively, although Blankenvoorde et al. demonstrates that a cystatin polypeptide is a therapeutically active substance, it is unnecessary for Blankenvoorde to disclose this functional property because this functional property (i.e., being a therapeutically active substance) of the cystatin as claimed and the known cystatin are inherently the same. The discovery of a previously unappreciated property of a prior art composition, or a scientific explanation for the prior art’s functioning, does not render the old composition patentably new to the discoverer. Atlas Powder Co. v. Ireco Inc., 190 F.3d 1342, 1347, 51 USPQ2d 1943, 1947 (Fed. Cir. 1999). Thus, the claiming of a new functional property (i.e., being a therapeutically active substance) which is inherently present in the prior art does not necessarily make the claim patentable. In re Best, 562 F.2d 1252, 1254, 195 USPQ 430, 4333 (CCPA 1977). Therefore, the disclosure of Blankenvoorde et al. satisfies the claim limitations as recited in instant claim 44.
For claims 46 and 54, with respect to where the inhibitor is stable in glycerol and other glycol-free environments:
As discussed supra for claims 38 and 51, Blankenvoorde et al. expressly discloses a cystatin polypeptide, and one that exhibits cysteine peptidase inhibition. It is noted that the scope of claims 46 and 54 does not require that the inhibitor is in a composition with glycerol or other glycol-free environments. Rather, the scope of claims 46 and 54 only requires that the inhibitor exhibits the physical property of stability when in glycerol or other glycol-free environments. In light of this interpretation, since Blankenvoorde discloses the claimed structure of a cystatin polypeptide, then the physical property (i.e., stability when in glycerol or other glycol-free environments) of the claimed cystatin polypeptide is inherently met since the property is not a structural limitation. Pursuant to MPEP 2112.01(II), “[p]roducts of identical chemical composition cannot have mutually exclusive properties.” In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). A chemical composition and its properties are inseparable.
Furthermore, although Blankenvoorde et al. does not examine the stability of any cystatin polypeptide in glycerol or other glycol-free environments, it is unnecessary for Blankenvoorde to disclose this physical property because this physical property (i.e., stability when in glycerol or other glycol-free environments) of the cystatin as claimed and the known cystatin are inherently the same. The discovery of a previously unappreciated property of a prior art composition, or a scientific explanation for the prior art’s functioning, does not render the old composition patentably new to the discoverer. Atlas Powder Co. v. Ireco Inc., 190 F.3d 1342, 1347, 51 USPQ2d 1943, 1947 (Fed. Cir. 1999). Thus, the claiming of a new physical property (i.e., stability when in glycerol or other glycol-free environments) which is inherently present in the prior art does not necessarily make the claim patentable. In re Best, 562 F.2d 1252, 1254, 195 USPQ 430, 4333 (CCPA 1977). Therefore, the disclosure of Blankenvoorde et al. satisfies the claim limitation as recited in instant claims 46 and 54.
For claim 57, with respect to where the inhibitor is formulated for administration to any one or more of the oral cavity, sinuses, upper and lower respiratory tract:
As discussed supra for claims 41, 47, and 56, Blankenvoorde et al. demonstrates that chicken cystatin, salivary cystatin S, and specific cystatin S fragments inhibit P. gingivalis growth, which would treat periodontitis. Blankenvoorde et al. also discloses that these polypeptides can protect the oral cavity against infection with P. gingivalis and can be used to design new therapeutic agents for the improvement of oral health (See Blankenvoorde article, pg. 1374, col. 1, 4th paragraph). To determine the antibacterial activity cystatins and fragments thereof, Blankenvoorde added the cystatin in culture with the bacteria, e.g., P. gingivalis. As such, Blankenvoorde et al. discloses the cystatins in a liquid form, i.e., culture.
Although Blankenvoorde et al. does not expressly disclose a cystatin as formulated for administration to an oral cavity, sinuses, and upper and lower respiratory tract, it is unnecessary for Blankenvoorde to disclose this intended use because an intended use of the cystatin polypeptide (i.e., for administration to an oral cavity, sinuses, and upper and lower respiratory tract) does not state a condition that is material to patentability or provide a structural limitation that would further limit the claimed cystatin polypeptide. The court has found that the determination of whether clauses such as “wherein” and “whereby" is a limitation in a claim is dependent on the specific facts of the case. If the “wherein" or “whereby” clause limits a process claim where the clause gives meaning and purpose to the manipulative steps, it should be given patentable weight. However, the court also found (quoting Minton v. Nat’l Ass’n of Securities Dealers, Inc., 336 F.3d 1373, 1381, 67 USPQ2d 1614, 1620 (Fed. Cir. 2003)) that a “‘whereby clause in a method claim is not given weight when it simply expresses the intended result of a process step positively recited.’” In the instant case, it is noted that the scope of claim 57 requires that the cystatin be in a form suitable or capable of administration to an oral cavity, sinuses, or upper and lower respiratory tract. As discussed supra, Blankenvoorde discloses the cystatin in a liquid form. Thus, the intended use of the cystatin polypeptide (i.e., for administration to an oral cavity, sinuses, and upper and lower respiratory tract) gives little meaning and purpose to the structure of the claimed polypeptide since Blankenvoorde discloses the necessary structure. Therefore, claim 57 recites an intended use that does not render material to patentability. Thus, the disclosure of Blankenvoorde et al. satisfies the claim limitation as recited in instant claim 57.
Accordingly, the disclosure of Blankenvoorde et al. anticipates instant claims 38, 41-42, 44, 46-47, 51, 54, and 56-57.
Claims 38, 41-42, 44, 46-47, 51, 54, and 56-57 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Altier et al. WO 2005/030967 A2 published on April 7, 2005.
For claims 38, 42 and 51, with respect to a cysteine peptidase inhibitor of natural origin comprising a cystatin polypeptide as recited in instant claims 35 and 51; and with respect to where the inhibitor is obtained from natural raw materials such as rice as recited in instant claim 42:
Altier et al. discloses compositions comprising nucleotide and/or amino acid sequences for 38 homologs of cysteine proteinases from maize, wheat, rice and soybean as depicted in Table 1 (See Altier, pg. 16, last paragraph; pg. 69, last paragraph). These plant cystatin genes and amino acid sequences are characterized by their cysteine proteinase inhibitory activity (See Altier, pg. 16, last paragraph). Proteinases are also called proteases and peptidases interchangeably (See Altier, pg. 16, last paragraph). Table 1 depicts 14 maize cystatin amino acid sequences, i.e., SEQ ID NOs: 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, and 26, 9 soybean cystatin amino acid sequences, i.e., SEQ ID NOs: 28, 30, 32, 34, 36, 38, 40, 42, and 44, 6 rice cystatin amino acid sequences, i.e., SEQ ID NOs: 46, 48, 50, 52, 54, and 56, and 13 wheat cystatin amino acid sequences, i.e., SEQ ID NOs: 58, 60, 62, 64, 66, 68, 70, 72, 74, and 76 (See Altier, Table 1). Altier et al. defines “full-length sequence” as referring to the entire amino acid sequence of, a native, (non-synthetic), endogenous, biologically active form of the specified protein (See Altier, pg. 4, last paragraph). As such, each of the full length amino acid sequences described in Table 1 encompass an amino acid sequence of natural origin derived from maize, soybean, rice, and wheat. Thus, each cystatin full length amino acid sequence including the 9 soybean and 6 rice cystatin sequences constitute a cysteine peptidase inhibitor of natural origin comprising at least a cystatin polypeptide as recited in instant claims 38 and 51, which is obtained from natural raw materials such as soybean, rice or other substances of natural plant origin as recited in instant claim 42.
Although Altier et al. expressly discloses that any of the cystatin amino acid sequences described in Table 1 exhibit the function of cysteine peptidase inhibition, it is unnecessary for Altier to disclose this function. The functional property (i.e., exhibiting cysteine peptidase inhibition) of the cystatin as claimed and the known cystatin are inherently the same. The discovery of a previously unappreciated property of a prior art composition, or a scientific explanation for the prior art’s functioning, does not render the old composition patentably new to the discoverer. Atlas Powder Co. v. Ireco Inc., 190 F.3d 1342, 1347, 51 USPQ2d 1943, 1947 (Fed. Cir. 1999). Thus, the claiming of a new functional property (i.e., exhibiting cysteine peptidase inhibition) which is inherently present in the prior art does not necessarily make the claim patentable. In re Best, 562 F.2d 1252, 1254, 195 USPQ 430, 4333 (CCPA 1977). Therefore, the disclosure of Altier et al. satisfies the claim limitations as recited in instant claims 38, 42 and 51.
For claims 41, 47, and 56, with respect to where the inhibitor is useful in treatment of periodontitis in human and veterinary medicine:
Altier et al. discloses that the compositions of the invention are useful as pharmaceutical compounds to provide treatment for diseases and disorders associated with fungal or microbial pathogens in humans and other animals (See Altier, pg. 73, 3rd to 4th paragraph). Although, Altier et al. does not expressly disclose that a plant cystatin is useful in treatment of periodontitis in human and veterinary medicine, it is unnecessary for Altier to disclose this intended use because an intended use of the cystatin polypeptide (i.e., useful in treatment of periodontitis in human and veterinary medicine) does not state a condition that is material to patentability or provide a structural limitation that would further limit the claimed cystatin polypeptide. The court has found that the determination of whether clauses such as “wherein” and “whereby" is a limitation in a claim is dependent on the specific facts of the case. If the “wherein" or “whereby” clause limits a process claim where the clause gives meaning and purpose to the manipulative steps, it should be given patentable weight. However, the court also found (quoting Minton v. Nat’l Ass’n of Securities Dealers, Inc., 336 F.3d 1373, 1381, 67 USPQ2d 1614, 1620 (Fed. Cir. 2003)) that a “‘whereby clause in a method claim is not given weight when it simply expresses the intended result of a process step positively recited.’” In the instant case, the intended use of the cystatin polypeptide (i.e., useful in treatment of periodontitis in human and veterinary medicine) gives little meaning and purpose to the structure of the claimed polypeptide. Therefore, claims 41, 47, and 56 recite an intended use that does not render material to patentability. Thus, the disclosure of Altier et al. satisfies the claim limitations as recited in instant claims 41, 47, and 56.
For claim 44, with respect to where the inhibitor is a therapeutically active substance:
As discussed supra for claims 38, 41-42, 47, 51, and 56, Altier et al. discloses that each cystatin described in Table 1 functions as a cysteine peptidase inhibitor and is useful for treatment of fungal and microbial pathogens in humans and other animals. As such, these cystatins exhibit a therapeutic effect thereby constituting a therapeutically active substance.
Additionally and/or alternatively, although Altier et al. discloses a cystatin polypeptide as a therapeutically active substance, it is unnecessary for Altier to disclose this functional property because this functional property (i.e., being a therapeutically active substance) of the cystatin as claimed and the known cystatin are inherently the same. The discovery of a previously unappreciated property of a prior art composition, or a scientific ex