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 .
Priority
Instant application 17/799,550 filed on 08/12/2022 claims benefit as follow:
CONTINUING DATA:
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Status of the Application
The amendment filled on 07/14/2025 has been entered.
Claims 1, 5-8, 11, 14-19, 23-24, 30-31, 34, 39, and 87-90 are pending.
Election/Restrictions
Applicant’s election, without traverse, of Group I, directed to a method to prevent or inhibit proliferation, growth and formation, or survival of protozoans, bacteria, or fungal cells, comprising administering a synthetic lysine analog, derivative, mimetic, or prodrug, in the reply filed on 07/14/2025 is acknowledged.
Regarding species election, Applicant’s election, of tranexamic acid and P. falciparum, P. berghei, and Leishmania, with traverse in the reply filed on 07/14/2025 is acknowledged.
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Applicant argues that the species form a single general inventive concept. Applicant submitted that a person having ordinary skill in the art would recognize that each of the claimed synthetic lysine analogs, derivatives, mimetics, or prodrugs prevents or inhibits proliferation, growth and formation, and survival each of protozoans, bacteria, or fungal cell species by occupying binding sites of lysine residues required for cell growth and replication.
Applicant’s arguments have been considered but are not found persuasive.
It is examiner position that these species lack unity of invention because they are not so linked as to form a single general inventive concept under PCT Rule 13.1.
For example, there are many possible derivatives of synthetic lysine, it would not be clear to one of ordinary skill which lysine derivatives are encompassed by the instant claims. Further, one of ordinary skill would need additional experimentations to determine which derivatives are suitable for use in the recited method. Further, one of ordinary skill would recognize that is it almost impossible that all derivatives, including compounds with distinct side groups or heteroatoms would be capable of performing the desired functions.
However, the species election is only for a search purpose.
In addition, please note that examiner requested election of one species of protozoans, bacteria or fungal cell.
Applicant elected three species of protozoans: P. falciparum, P. berghei, and Leishmania.
Therefore, it seems that Applicant consider the elected species as obvious variants of each other.
Examination will begin with the elected species. In accordance with the MPEP 803.02, if upon examination of the elected species, no prior art is found that would anticipate or render obvious the instant invention based on the elected species, the search of the Markush-type claim will be extended. If prior art is then found that anticipates or renders obvious the non-elected species, the Markush-type claim will be rejected. It should be noted that the prior art search will not be extended unnecessarily to cover all non-elected species. Should Applicant overcome the rejection by amending the claim, the amended claim will be reexamined. The prior art search will be extended to the extent necessary to determine patentability of the Markush-type claim. In the event prior art is found during reexamination that renders obvious or anticipates the amended Markush-type claim, the claim will be rejected and the action made final.
Claim Objections
Claim 18 is objected to because of the following informalities:
“The method claims 11” should be replaced by “the method of claim 11”.
Claim 5 is objected to because this claim recites “AZD 6564”, which is an abbreviation. This is the first time appears in the claims and needs to be spelled out in its entirety and must be defined.
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 1, 6, 7, 8, 11, 14, 15, 16, 17, 18, 19, 23, 24, 30, 31, 34, 39, 88, 89 and 90 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 applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
The claims contain subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor(s), at the time the application was filed, had possession of the claimed invention.
The MPEP states that the purpose of the written description requirement is to ensure that the inventor had possession, as of the filing date of the application, of the specific subject matter later claimed. The courts have stated that, “To fulfill the written description requirement, a patent specification must describe an invention and do so in sufficient detail that one skilled in the art can clearly conclude that “the inventor invented the claimed invention.” Lockwood v. American Airlines, Inc., 107 F.3d 1565, 1572, 41 USPQ2d 1961, 1966 (Fed. Cir. 1997); In re Gostelli, 872 F.2d 1008, 1012, 10 USPQ2d 1614, 1618 (Fed. Cir. 1989) (“[T]he description must clearly allow persons of ordinary skill in the art to recognize that [the inventor] invented what is claimed.”). Thus, an applicant complies with the written description requirement “by describing the claimed invention with all of its limitations using such descriptive means as words, structures, figures, diagrams, and formulas that fully set forth the claimed invention.” Lockwood, 107 F.3d at 1572, 41 USPQ2d at 1966.” Regents of the University of California v. Eli Lilly & Co., 43 USPQ2d 1398.
Further, for a broad generic claim, the specification must provide adequate written description to identify the genus of the claim. In Regents of the University of California v. Eli Lilly & Co. the court stated that, “A written description of an invention involving a chemical genus, like a description of a chemical species, ‘requires a precise definition, such as by structure, formula, [or] chemical name,’ of the claimed subject matter sufficient to distinguish it from other materials.” Fiers, 984 F.2d at 1171, 25 USPQ2d 1601; In re Smythe, 480 F.2d 1376, 1383, 178 USPQ 279, 284985 (CCPA 1973) (“In other cases, particularly but not necessarily, chemical cases, where there is unpredictability in performance of certain species or subcombinations other than those specifically enumerated, one skilled in the art may be found not to have been placed in possession of a genus …”) Regents of the University of California v. Eli Lilly & Co., 43 USPQ2d 1398.
The MPEP lists factors that can be used to determine if sufficient evidence of possession has been furnished in the disclosure of the Application. These include level of skill and knowledge in the art, partial structure, physical and/or chemical properties, functional characteristics alone or coupled with a known or disclosed correlation between structure and function, and the method of making the claimed invention. Disclosure of any combination of such identifying characteristics that distinguish the claimed invention from other materials and would lead one of skill in the art to the conclusion that the applicant was in possession of the claimed genus is sufficient. See MPEP § 2163. While all of the factors have been considered, a sufficient amount for a prima facie case are discussed below.
The instant claims are drawn to a method of a method to prevent or inhibit proliferation, growth and formation, or survival of protozoans, bacteria, or fungal cells, the method comprising: administering a composition comprising a synthetic lysine analog, derivative, mimetic, or prodrug, wherein the synthetic lysine analog, derivative, mimetic, or prodrug interacts with the protozoans, bacteria, or fungal cells to prevent or inhibit proliferation, growth and formation, or survival of the protozoans, bacteria, or fungal cells, wherein the administration disrupts at least one of protein-protein, protein-DNA, or protein-RNA interaction by antagonizing at least one of lysine, arginine, or histidine residues on a protein, inhibits proliferation, growth and formation, or survival of the protozoans, bacteria, or fungal cells by occupying binding sites of lysine residues required for proliferation, growth and formation, or survival of the protozoans, bacteria, or fungal cells or deprives lysine or arginine from a biosynthetic pathway required by the protozoans, bacteria, or fungal cells to thereby inhibit proliferation, growth and formation, or survival of the protozoans, bacteria, or fungal cells.
However, the genus of “a synthetic analog, derivative, mimetic and prodrug” is not fully structurally defined.
The instant claims are directed to "lysine analogs, derivatives, mimetics and prodrugs" which are only defined by function.
The instant invention is not commensurate in scope with the pending claims because, without further experimentations, it is not clear which "lysine analogs, derivatives, mimetics and prodrugs" are suitable for preventing or inhibiting proliferation, growth and formation, or survival of protozoans, bacteria or fungal cells.
The recitation of a “derivative” is not clearly defined in the specification, and therefore does not set forth the metes and bounds of the term “derivative”. The Merriam-Webster’s Online Dictionary defines “derivative” as “a chemical substance related structurally to another substance and theoretically derivable from it” and an “analogue” as “a chemical compound that is structurally similar to another but differs slightly in composition (as in replacement of one atom by an atom of a different element or in the presence of a particular functional group).”
One of ordinary skill in the art would recognize that a "derivative" or an “analog” would read on compounds having any widely varying groups that could be used to substitute the compound. Any significant structural variation to a compound would be reasonably expected to alter its properties, e.g. physical, chemical, physiological effects and functions.
Further, as to the claimed “mimetic or prodrug”, no specific examples are given that would demonstrate which ‘‘mimetics or prodrugs” are useful for the recited method.
The examples provided in the instant specification are limited to tranexamic acid (TXA).
BERETICH (WO-199712582-A2) discloses a method for preventing and treating, coccidiosis (coccidiosis is a parasitic infection caused by protozoa) by administering a lysine analog (see abstract).
BERETICH teaches and claims the following lysine analogs (see claim 2) for combating a parasitic disease caused by protozoan (see claim 12):
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In addition, WULF (WO-20000037071) teaches additional analogs of lysine (see page 4 lines 21-30):
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However, the instant claims are not limited to the above compounds and recites any lysine analogs, derivatives, mimetics and prodrugs.
Medicinal chemistry is an experimental science with a low predictable level. Small changes in the structure of a compound can lead to large differences in their pharmacological activity.
"[A] patentee of a biotechnological invention cannot necessarily claim a genus after only describing a limited number of species because there may be unpredictability in the results obtained from species other than those specifically enumerated”. See Noelle v. Lederman, 355 F.3d 1343, 1350, 69 USPQ2d 1508, 1514 (Fed. Cir. 2004).
It is generally accepted in the art that formation of a particular “prodrugs,” for a given compound or series of compounds is unpredictable.
As stated by Stella et al., (Prodrugs: Challenges and Rewards, Part 1, 2007), the personnel and skills needed for a successful prodrug program “are no different from those for analog development – it takes a team. The ideal drug is one that is active, easy to formulate, well absorbed after oral dosing, has an acceptable PK profile, and is both renally cleared and metabolized to 1-2 non-toxic metabolites that are rapidly excreted after being formed. If a prodrug intervention is necessary, obviously this ideal scenario is not met. The ideal prodrug, therefore, is one that readily achieves its desired goal, is non-toxic, and breaks down efficiently and quantitatively to the drug and to know and safe by products. Like the drug discovery process, this goal is not often met” (Page 24, Paragraph 3).
Although attempts have been made to predict drug metabolism, this is still an experimental science. For a compound to be a prodrug, it must meet three tests. First, the prodrug must itself be biologically inactive. Second, the prodrug must be metabolized to a second substance in a human at a rate and to an extent to produce that second substance at a physiologically meaningful concentration. Thirdly, that second substance must be biologically active. Finding a prodrug is an empirical exercise. Predicting if a certain ester of a claimed alcohol, for example, is in fact a prodrug, and produces the active compound metabolically, in man, at a therapeutic concentration and at a useful rate, is filled with experimental uncertainty.
Methods of synthesizing compounds are, in general, known to the person of ordinary skill, however methods of making the myriads of compounds embraced by the instant claims is beyond the skill of the artisan, particularly when certain elements, such as “analogs, derivatives, mimetics and prodrugs" are merely described partially.
As such, the instant specification and instant claims do not provide sufficient description such that one could anticipate which compounds are useful in the recited method.
The description requirement of the patent statue requires a description of an invention, not an indication of a result that one might achieve if one made that invention. See In re Wilder, 736, F.2d 1516, 1521, 222 USPQ 369, 372-73 (Fed. Cir. 1984) (affirming rejection because the specification does “little more than outlin[e] goals appellants hope the claimed invention achieves and the problems the invention will hopefully ameliorate.”) Accordingly, it is deemed that the specification fails to provide adequate written description for the genus of the claims and does not reasonably convey to one skilled in the relevant art that the inventor(s), at the time the application was filed, had possession of the entire scope of the claimed invention.
Substantial and undue experimentations would be needed to practice the whole scope of Applicant’s invention because the specification lacks sufficient detail to show which analogs, derivatives, mimetics and prodrugs are suitable for the recited method.
Further, there is no guarantee that all the compounds embraced by the scope of the instant claims would be useful for prevention of proliferation of protozoans, bacteria or fungal cells.
The MPEP states that written description for a genus (for example, the claimed prodrugs, or derivatives of the elected compound species) can be achieved by a representative number of species within a broad generic. In the instant case, however, the Specification does not disclose a sufficient variety of species to reflect this variance in the genus because the examples provided in the instant specification are limited to tranexamic acid (TXA).
The rejection would be overcome by amending the claims to add structural limitation, e.g., adding general formula or list of specific compounds capable of performing the desired function.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1, 5, 6, 34, 89 and 90 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by BERETICH (WO-199712582-A2).
This rejection applies to expanded species.
BERETICH discloses a method for preventing and treating parasitic disease, caused by a protozoan, comprising administering a lysine analog (see abstract and claim 12).
Regarding instant claim 5, BERETICH teaches e.g., epsilon-aminocaproic acid (see claim 2):
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Regarding instant claims 6, 89 and 90, BERETICH teaches and claims Plasmodium and Leishmania:
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Regarding instant claim 34, BERETICH teaches administering through animal’s diet:
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Animal’s diet is administered at least once a day. Further, regarding instant claim 34, BERETICH teaches:
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Since the disclosure of BERETICH meets all the limitations of instant claims 1, 5, 6, 34, 89 and 90 those claims are anticipated.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
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 1, 5-8, 11, 14-19, 23-24, 30-31, 34, 39, and 87-90 are rejected under 35 U.S.C. 103 as being unpatentable over BERETICH (WO-199712582-A2) in view of WULF (WO-20000037071) evidenced by Kelly (Kelly M, Su CSchaber C, Crowley JR, Hsu F, Carlson JR, Odom AR 2015. Malaria Parasites Produce Volatile Mosquito Attractants. mBio 6:10.1128/mbio.00235-15).
The teachings of BERETICH (WO-199712582-A2) have been discussed above and are incorporated herein by reference.
Regarding instant claims 7 and 88, BERETICH does not explicitly teach P. falciparum.
However, BERETICH teaches and claims treatment of malaria.
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As evidenced by Kelly, P. falciparum is being responsible for the most severe cases of malaria, therefore one of ordinary skill in the art would be motivated to use the method disclosed by BERETICH against P. falciparum.
Regarding claim 8, BERETICH does not explicitly teach a solution that contains about 37 mM to about 75 mM concentration of the synthetic lysine analog, derivative, mimetic or prodrug.
Regarding claim 11, BERETICH does not explicitly teach solutions (according to IUPAC definition, solutions are homogeneous mixtures of substances in solid, liquid, or gas states; BERETICH does not explicitly teach the disclosed compositions are homogeneous).
Regarding claims 14 and 30, BERETICH does not teach administration every 8 hours.
Regarding claims 15 and 16, BERETICH does not teach wherein the solution is administrated as initial bolus followed by continues infusion.
Regarding claims 17 and 31, BERETICH does not teach the recited number of days.
Regarding claim 18, BERETICH does not explicitly teach administration until an infection is resolved.
Regarding claim 19, BERETICH does not teach application as part of a vehicle which adapts to human skin.
Regarding claim 23 and 24, BERETICH does not teach topical administration every 8 hour and BERETICH is silent about the solution being administered topically until an infection has been resolved.
Regarding claim 39, BERETICH does not teach administering is performed systematically.
However, a person of ordinary skill would have been capable of further improving the composition, dose regime and administration methods through routine experimentations because BERETICH teaches and claims a lysine analog administrated orally for treatment of the same conditions as recited in instant claims:
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BERETICH teaches:
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BERETICH teaches and claims (see claim 9):
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BERETICH teaches a lysine analogs administered by injections (page 2, second paragraph):
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A person of ordinary skill would have been motivated and capable of further improving the composition, dose regime and administration methods through routine experimentations. The skilled artisan would have been motivated to use the method until the infection is resolved.
Regarding claim 87, BERETICH does not explicitly teach using tranexamic acid in the disclosed method.
However, BERETICH teaches tranexamic acid is a lysine analog (see claim 2):
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Applying KSR prong (B) - it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to substitute EACA for tranexamic acid with a reasonable expectation of success. The skilled artisan would have been motivated to test additional lysine analog and tranexamic acid is well known lysine analog that is used for the same purposes as EACA.
The deficiencies are further cured by WULF.
WULF teaches treatments of skin diseases (see abstract):
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WULF teaches the diseases are induced by bacteria, fungi or other microorganisms (see page 17):
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WULF teaches tranexamic acid (see page 12):
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WULF teaches (see page 8):
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Regarding claim 11, WULF teaches solutions (see page 8, line 10):
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Regarding instant claim 19, WULF teaches topical treatments (see title).
Further, regarding claim 19, WULF teaches a vehicle which adopts to human skin (a vehicle which facilitate the absorption of an active medication) (see page 6):
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Regarding claim 23 and 24, WULF teaches application “more times a day” (see pages 26/27):
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WULF does not teach the solution is administered every 8 hours, however, WULF teaches “more times a day”, thus, a person of ordinary skill would have been motivated and capable of further improving the administration regime through routine experimentations.
Further, applying KSR prong (A) - it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of BERETICH and use the composition disclosed by WULF topically until an infection has been resolved with a reasonable expectation of success. The skilled artisan would have been motivated to treat skin diseases because WULF teaches tranexamic acid is suitable for treatment of skin diseases induced by bacteria, fungi or other microorganisms.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to IZABELA SCHMIDT whose telephone number is (703)756-4787. The examiner can normally be reached Monday - Friday from 9 am to 5 pm.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Clinton A Brooks can be reached at (571)270-7682. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/I.S./Examiner, Art Unit 1621
/CLINTON A BROOKS/Supervisory Patent Examiner, Art Unit 1621