DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Priority
Acknowledgments are made that this application claims the priority to the following:
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Information Disclosure Statement
The information disclosure statement (IDS), dated 05/26/2023 and 09/15/2023, comply with the provisions of 37 CFR 1.97, 1.98 and MPEP § 609. Accordingly, they have been placed in the application file and the information therein has been considered as to the merits.
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 1-6 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception in the form of a naturally occurring polypeptide without significantly more. The claim recite a peptide of formula (I) and its species, represented by SEQ ID NOs: 1-6. However, applicants claimed sequences read upon or part of a naturally occurring protein from Bothrops jararacussau (Jararacussu), see below
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, see attached Q90249 – PA1H1_BOTJR, 2008 document from UniProt.
In the above underlined sequences, viz., SLFELGMILQET, align with 100% identity to applicants sequences.
However, mere cleavage of peptide bonds is insufficient to demonstrate a difference from the full-length protein, similar to isolated DNA ruled to be ineligible in Ass’n for Molecular Pathology v. Myriad Genetics, Inc., 569 U.S. 576, 589-91, 106 USPQ2d 1972, 1978-79 (2013). There is no indication from the claims that any function is found in claimed sequences that is distinct from the full-length protein.
The specification makes clear that the function of claimed sequences in modulation of amyloid-beta protein. However, N-terminal sequences of above shown sequences found to stimulate the activity of neprilysin, as well as stimulating the activity of ECE1 in cerebrospinal fluids of Alzheimer’s patients as evidenced from Smith et al [Scientific Reports, 2016, 6, 22413, 1-10]. So, the claims fail to show that the function of the claimed sequeces are distinct from the parent protein.
This judicial exception is not integrated into a practical application because there are no practical applications found within the rejected claims. The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception because there are no other additional elements in the rejected claims.
Since the claims recite fragments of naturally occurring proteins, offer no differences other than cleavage of peptide bonds, contain no practical applications, and do not recite any other elements that amount to significantly more than the judicial exception, the claims are rejected as being drawn to ineligible subject matter.
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.
I. Claims 8-10 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification/prior art, while being enabling for treating Alzheimer’s disease by administering SEQ ID NO:2, the specification does not reasonably provide enablement for preventing an individual having Alzheimer’s disease by administering all possible peptides covered by the claimed peptide represented by formula I. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to the invention commensurate in scope with these claims.
Attention is directed to In re Wands, 8 USPQ2d 1400 (CAFC 1988) at 1404where the court set forth the eight factors to consider when assessing if a disclosurewould have required undue experimentation. Citing Ex parte Forman, 230 USPQ 546(BdApls 1986) at 547 the court recited eight factors: (1) the nature of the invention; (2) the state of the prior art; (3) the relative skill of those in the art; (4) the predictability or unpredictability of the art; (5) the breadth of the claims; (6) the amount of direction or guidance presented; (7) the presence or absence of working examples; and, (8) the quantity of experimentation necessary.
(1, 5) The nature of the invention and the Breadth of the Claims:
Claims are drawn to:
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The meaning of “preventing” is completely eradicate the claimed disease, both existing as well as from the future occurrence.
The bread of the claims are encompass the prevention of complex Alzheimer’s disease in a subject which has potentially many different causes, each of which may or may not be addressed by the administration of the claimed sequences.
(2) The state of the prior art:
While the state of the art is relatively high with regard to delaying the progress of neurodegenerative disease, the state of the art with regard to prevention of such disorders is underdeveloped. In particular, there do not appear to be any examples or teachings in the prior art wherein a compound or peptide similar to the claimed peptide was administered to a subject to provide prevent development of Alzheimer’s disease. Illustration of the state of the art, Golden (Minnesota Medicine, 1995) on the abstract, teaches that even reaching the accurate diagnosis of Alzheimer’s disease is difficult and there is no cure yet for Alzheimer’s disease.
Pardo-Moreno [Pharmaceutics, 2022, 14(6), 1117, 1-20] in a review article states that the therapeutic approach to AD remains a challenge for researchers. Despite the advances that have been made in this field, we still do not have a treatment capable of halting the progress of the disease, as the therapies currently used have only achieved an improvement in the cognitive and behavioral deterioration of patients affected by this disease. In this sense, strategies based on the promotion of healthy lifestyles are indispensable in the prevention of the pathology, and these should be reinforced. Therefore, more research is needed to gain a more in-depth knowledge of AD, thus making it possible to identify new therapies that can contribute to its treatment. [see Abstract and Conclusions]
(3) The relative skill of those in the art:
The level of ordinary skill in the art of treating Alzheimer’s disease is high, however, as an ordinary artisan in this art needs specialized knowledge for preventing Alzheimer’s disease with the recited peptides.
(4) The predictability of the art:
Despite the advanced training of practitioners in the art, it is still impossible, to predict from the structure of a peptide(s) and from its functionality that the peptide or the composition comprising the peptide(s) will be useful in preventing a condition e.g. Alzheimer’s disease.
Absent a mechanistic link between the method steps and the observed effect, the pharmaceutical and medical treatment arts are highly unpredictable. Most progress is established through empirical and anecdotal evidence as to the efficacy of certain treatments. Once a mechanistic link has been established between the method and the mechanism of action become more predictable. However, many uncertainties can still exist even when the mechanism of action is known. For example, factors such as the bioavailability, pharmacokinetic profile, and potency of a compound can still be uncertain even if it can be expected to be active in disease models. The term "preventing" is interpreted as encompassing any improvement of the clinical outcome of a subject by administering the therapy prior to the occurrence of condition claimed. However, no working examples support administration of any composition prior to the occurrence of preventing Alzheimer’s disease as claimed to improve the clinical outcome.
It cannot be predicted from the prior art or from the specification that how the occurrence of any condition as claimed can be completely prevented by administration of the agents as claimed. It cannot be predicted from the prior art or from the specification that Alzheimer’s disease can be completely prevented as prevention embraces the complete 100% inhibition. In addition, it cannot be predicted from any prior art or from any drug treatment that any condition can be completely prevented from occurring again. Treatment of a condition is possible but not prevention of a condition. In other words, there is no guarantee that Alzheimer’s disease will not occur ever again after administration of an effective amount of recited peptides.
(6, 7) The amount of guidance given and the presence of working examples:
It has been established that, “The amount of guidance or direction needed to enable the invention is inversely related to the amount of knowledge in the state of the art as well as the predictability in the art.” In re Fisher, 427 F.2d 833, 839 166 USPQ 18, 24 (CCPA 1970).
There is no single example or evidence to the administration of the agents prior to the occurrence to prevent Alzheimer’s disease as claimed and the condition was completely prevented.
(8) The quantity of experimentation necessary:
Applicant fails to provide information sufficient to practice the claimed invention, absent undue experimentation. The burden of enabling the prevention of Alzheimer’s disease comprising administering the claimed agents would be much greater than that of enabling the treatment of such condition. In the instant case, the specification does not provide guidance as to how one skilled in the art would accomplish the objective of preventing Alzheimer’s disease for example or how the subject could be kept from ever being susceptible to Alzheimer’s disease. Nor is there any guidance provided as to a specific protocol to be utilized in order to show the efficacy of the presently claimed agents for preventing Alzheimer’s disease as claimed. Genetech, 108 F.3d at 1366 states that "a patent is not a hunting license. It is not a reward for search, but 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." Therefore, in conclusion, it is readily apparent from the aforementioned disclosure, in conjunction with a corresponding lack of scientific data and working embodiments regarding prevention of Alzheimer’s disease as claimed of is not enabled because the specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the invention commensurate in scope with these claims.
Suggested language to overcome above rejection: delete term “preventing” from the claim language.
II. Claims 13 and 22 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification/prior art, while being enabling for treating kidney inflammation and fibrosis in diabetic mice by administering SEQ ID NO:2, the specification does not reasonably provide enablement for treating and preventing an individual having all possible inflammations, fibrosis, lung diseases, hypertensions, pulmonary hypertensions, cardiovascular diseases and/or renovascular disease by administering all possible peptides covered by the claimed peptide represented by formula I. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to the invention commensurate in scope with these claims.
Attention is directed to In re Wands, 8 USPQ2d 1400 (CAFC 1988) at 1404where the court set forth the eight factors to consider when assessing if a disclosurewould have required undue experimentation. Citing Ex parte Forman, 230 USPQ 546(BdApls 1986) at 547 the court recited eight factors: (1) the nature of the invention; (2) the state of the prior art; (3) the relative skill of those in the art; (4) the predictability or unpredictability of the art; (5) the breadth of the claims; (6) the amount of direction or guidance presented; (7) the presence or absence of working examples; and, (8) the quantity of experimentation necessary.
(1, 5) The nature of the invention and the Breadth of the Claims:
Claims are drawn to:
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Clams read treating and preventing all possible recited diseases by administering all possible sequences of formula (I) in all possible conditions and mode of administrations.
The meaning of “preventing” is completely eradicate the claimed disease, both existing as well as from the future occurrence.
The bread of the claims are encompass the prevention of recited complex divergent diseases in a subject which has potentially many different root causes, each of which may or may not be addressed by the administration of the claimed sequences.
(2) The state of the prior art:
While the state of the art is relatively high with regard to treating recited disease, the state of the art with regard to prevention of such diseases is underdeveloped. In particular, there do not appear to be any examples or teachings in the prior art wherein a peptide similar to the claimed peptide was administered to a subject to provide prevent development of recited diseases.
(3) The relative skill of those in the art:
The level of ordinary skill in the art of treating Alzheimer’s disease is high, however, as an ordinary artisan in this art needs specialized knowledge for preventing Alzheimer’s disease with the recited peptides.
(4) The predictability of the art:
Despite the advanced training of practitioners in the art, it is still impossible, to predict from the structure of a peptide(s) and from its functionality that the peptide or the composition comprising the peptide(s) will be useful in treating and preventing divergent recited diseases by administering all possible peptides of formula I.
With regard to variability in peptides, protein chemistry is probably one of the most unpredictable areas of biotechnology. Consequently, the effects of sequence dissimilarities upon protein structure and function cannot be predicted. Bowie et al (Science, 1990, 247:1306-1310) teach that an amino acid sequence encodes a message that determines the shape and function of a protein and that it is the ability of these proteins to fold into unique three-dimensional structures that allows them to function and carry out the instructions of the genome and further teaches that the problem of predicting protein structure from sequence data and in turn utilizing predicted structural determinations to ascertain functional aspects of the protein is extremely complex (column 1, page 1306). Bowie et al further teach that while it is known that many amino acid substitutions are possible in any given protein, the position within the protein's sequence where such amino acid substitutions can be made with a reasonable expectation of maintaining function are limited. Certain positions in the sequence are critical to the three dimensional structure/function relationship and these regions can tolerate only conservative substitutions or no substitutions at all (column 2, page 1306). The sensitivity of proteins to alterations of even a single amino acid in a sequence are exemplified by Burgess et al (J. Cell Biol. 111:2129-2138, 1990) who teach that replacement of a single lysine reside at position 118 of acidic fibroblast growth factor by glutamic acid led to the substantial loss of heparin binding, receptor binding and biological activity of the protein and by Lazar et al (Mol. Cell. Biol., 8:1247-1252, 1988) who teach that in transforming growth factor alpha, replacement of aspartic acid at position 47 with alanine or asparagine did not affect biological activity while replacement with serine or glutamic acid sharply reduced the biological activity of the mitogen. These references demonstrate that even a single amino acid substitution will often dramatically affect the biological activity and characteristics of a protein.
Absent a mechanistic link between the method steps and the observed effect, the pharmaceutical and medical treatment arts are highly unpredictable. Most progress is established through empirical and anecdotal evidence as to the efficacy of certain treatments. Once a mechanistic link has been established between the method and the mechanism of action become more predictable. However, many uncertainties can still exist even when the mechanism of action is known. For example, factors such as the bioavailability, pharmacokinetic profile, and potency of a compound can still be uncertain even if it can be expected to be active in disease models. The term "preventing" is interpreted as encompassing any improvement of the clinical outcome of a subject by administering the therapy prior to the occurrence of condition claimed. However, no working examples support administration of any composition prior to the occurrence of preventing recited divergent diseases as claimed to improve the clinical outcome.
It cannot be predicted from the prior art or from the specification that how the occurrence of any condition as claimed can be completely prevented by administration of the agents as claimed. It cannot be predicted from the prior art or from the specification that the recited diseases can be completely prevented as prevention embraces the complete 100% inhibition. In addition, it cannot be predicted from any prior art or from any drug treatment that any condition can be completely prevented from occurring again. Treatment of a condition is possible but not prevention of a condition. In other words, there is no guarantee that the recited diseases will not occur ever again after administration of an effective amount of recited peptides.
(6, 7) The amount of guidance given and the presence of working examples:
Shown data is limited SEQ ID NO:2 for treating kidney inflammation and fibrosis in diabetic mice.
It has been established that, “The amount of guidance or direction needed to enable the invention is inversely related to the amount of knowledge in the state of the art as well as the predictability in the art.” In re Fisher, 427 F.2d 833, 839 166 USPQ 18, 24 (CCPA 1970).
There is no single example or evidence to the administration of the agents prior to the occurrence to prevent recited disease as claimed and the condition was completely prevented.
(8) The quantity of experimentation necessary:
Applicant fails to provide information sufficient to practice the claimed invention, absent undue experimentation. The burden of enabling the prevention of recited diseases comprising administering the claimed peptides would be much greater than that of enabling the treatment of such condition. In the instant case, the specification does not provide guidance as to how one skilled in the art would accomplish the objective of preventing recited diseases for example or how the subject could be kept from ever being susceptible to recited diseases. Nor is there any guidance provided as to a specific protocol to be utilized in order to show the efficacy of the presently claimed peptides for preventing recited diseases as claimed. Genetech, 108 F.3d at 1366 states that "a patent is not a hunting license. It is not a reward for search, but 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." Therefore, in conclusion, it is readily apparent from the aforementioned disclosure, in conjunction with a corresponding lack of scientific data and working embodiments regarding prevention of recited diseases as claimed of is not enabled because the specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the invention commensurate in scope with these claims.
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 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 of this title, 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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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.
I. Claims 1-6 are rejected under 35 U.S.C. 103 as being unpatentable over Smith (Scientific Reports, 2016, 6, 22413, 1-10; see applicants filed IDS dated 09/15/2023).
Smith teaches the following peptide:
SLFELGKMILQETGKNPAKS [see Fig.4].
The underlined sequence reads applicants peptide of formula (I) and the dependent claims.
Smith teaches that their disclosed peptides enhance the activity of amyloid beta protein degrading proteases, such as NEP and ECE-1, which degrade amyloid beta in the brain. Smith further teaches that their disclosed peptides are potential novel drug lead in the fight against Alzheimer’s disease. [See abstract].
The difference is that peptide of Smith is longer than the claimed peptide. This can be cured with the following reasoning:
Applicants specification defined the property of claimed peptide, which significantly induce increase in NEP activity. Smith identified the fragment of myotixin II of B.asper, which enhance the activity of amyloid beta protein degrading proteases through a routine experimentation. Therefore, similarly a skilled person in the art would be motivated to further optimize the length of sequence or eliminate unwanted sequence in the peptide through a routine experimentation.
Based on the above established facts from the cited prior art, it appears that all the claimed elements, i.e, applicants peptide sequences and their properties, were known in the prior art, and one skilled person in the art could have combined the elements as claimed by known relationships, with no change in their respective functions, and the combination would have yielded predictable results to one of ordinary skill in the art.
The motivation to modify the art can arise from the expectation that the prior art teachings will perform their expected functions to achieve their expected results when combined for their common known purpose. See MPEP 2144.07. Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention by taking the advantage of the teaching of the above cited reference and to make the instantly claimed peptides with a reasonable expectation of success.
II. Claims 8-10 are rejected under 35 U.S.C. 103 as being unpatentable over Smith (Scientific Reports, 2016, 6, 22413, 1-10; see applicants filed IDS dated 09/15/2023) in view of Shiraki (J.Biochem., 2002, 132, 591-595).
For claim 8:
Smith teaches a method, wherein the peptide, viz., SLFELGKMILQETGKNPAKS [see Fig.4], enhances the activity of amyloid beta protein degrading proteases, such as NEP and ECE-1, which degrade amyloid beta in the brain. Smith further teaches that their disclosed peptides are potential novel drug lead in the fight against Alzheimer’s disease. [See abstract].
The underlined sequence reads applicants peptide of formula (I) and the dependent claims.
Differences between Smith and instant claim are as follows:
(i) Peptide of Smith is longer than the claimed peptide.
(ii) Smith is silent on method of treating Alzheimer’s disease.
With regard to (i) of above, applicants specification defined the property of claimed peptide, which significantly induce increase in NEP activity. Smith identified the fragment of myotixin II of B.asper, which enhance the activity of amyloid beta protein degrading proteases through a routine experimentation. Therefore, similarly a skilled person in the art would be motivated to further optimize the length of sequence or eliminate unwanted sequence in the peptide through a routine experimentation.
With regard to (ii) of above, Smith in their disclosure stated that their disclosed peptides are potential novel drug lead in the fight against Alzheimer’s disease [See abstract]. Therefore, a skilled person in the art would be motivated to develop a method of treating Alzheimer’s disease by administering the claimed peptides.
With regard to claims 9 and 10:
Smith is silent on additional active agents, such as L-Arg, L-Gln or an antioxidant etc., in their disclosure. This can be cured from the teachings of Shiraki, which teaches arginine exhibits the best results in preventing the formation of aggregates and further states that effect of arginine is not dependent on the size or isoelectric point of eight kinds of proteins rested [see abstract]. Therefore, one would be motivated to include arginine the treatment of Alzheimer’s disease, this disease is also results from the aggregation of amyloid protein.
Based on the above established facts from the cited prior art, it appears that all the claimed elements, i.e, applicants peptide sequences and their properties and advantages of Arg in treating AD, were known in the prior art, and one skilled person in the art could have combined the elements as claimed by known relationships, with no change in their respective functions, and the combination would have yielded predictable results to one of ordinary skill in the art.
The motivation to modify and combine the art can arise from the expectation that the prior art teachings will perform their expected functions to achieve their expected results when combined for their common known purpose. See MPEP 2144.07. Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention by taking the advantage of the teaching of the above cited reference and to make the instantly claimed method with a reasonable expectation of success.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SUDHAKAR KATAKAM whose telephone number is (571)272-9929. The examiner can normally be reached 8:30 am to 5 pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Melissa Fisher can be reached at 571-270-7430. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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SUDHAKAR KATAKAM
Primary Examiner
Art Unit 1658
/SUDHAKAR KATAKAM/Primary Examiner, Art Unit 1658