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 .
Election/Restrictions
Applicants’ election with traverse of Group II, claimed in claims 10-22, in the reply filed on 7/27/26 is acknowledged. The traversal is on the ground(s) that the cyclic peptide of Sun et al. does not meet the limitations of cyclic peptide of claim 1. Applicants argue that the cyclic peptide of Sun et al. is 14 amino acids in length and targets PD-L1, while the instantly claimed peptide is 11 amino acids in length and targets RAS. This was found persuasive, however WO2013/100132 teaches a cyclic peptide that meets the limitations of the cyclic peptide of claim 1. WO2013/100132 discloses DP-66 is an 11 residue cyclic peptide that is within the scope of claims 1, 10 and 15. Therefore, the technical feature is not a special technical feature in view of the art.
The requirement is still deemed proper and is therefore made FINAL.
Applicants elected:
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2. Compound 1201:
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3. Treatment or prevention of cancer
4. Lung cancer (specific type of cancer).
5. KRAS mutant G12C (specific RAS mutation).
After further consideration, the election of species requirement is withdrawn.
Claims 1-22 are pending.
Claims 1-9 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected group, there being no allowable generic or linking claim.
Claims 10-22 read on the elected Group II and are under consideration.
Claim Objections
Claim 21 is objected to because of the following informalities: Claim 21 references a Table. MPEP 2173.05(S) states: Where possible, claims are to be complete in themselves. Incorporation by reference to a specific figure or table “is permitted only in exceptional circumstances where there is no practical way to define the invention in words and where it is more concise to incorporate by reference than duplicating a drawing or table into the claim.
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 10-22 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 pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
MPEP § 2137 states that "the written description requirement for a genus must be satisfied through sufficient description of a representative number of species by actual reduction to practice, reduction to drawings, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus (see i)(C), above). See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406.
For written description, the analysis (a) considers actual reduction to practice, (b) disclosure of drawings or structural chemical formulas, (c) sufficient relevant identifying characteristics in the way of complete/partial structure or physical and/or chemical properties, functional characteristics when coupled with known or disclosed and (d) representative number of examples.
Claim 10 is drawn to a method for treating or preventing cancer comprising administering to a subject in need thereof the pharmaceutical composition according to claim 1 (formula 1). Claim 15 is drawn to a method of treating or preventing a disease with formula (1). Claims 1 and 15 claim a large genus of cyclic peptides defined by different amino acid side chains, N-substituents, cyclization/linker groups and further defines the cyclic peptides for the treatment and prevention of cancer (claim 10) or any disease (claim 15).
Actual reduction to practice and (b) disclosure of drawings or structural chemical formulas:
Examiner notes that even though Applicant has reduced to practice some compounds that have the general core structure of the Formula of claim 1, Applicant has not reduced to practice a representative number of species that are covered by all the variables recited in the instant claims The breadth of claim 1 is substantial because the claim permits numerous independent variables at multiple positions within the peptide. The possible combination of those variables generates an extremely large number of cyclic peptide species, exceeding the limited number exemplified and biologically characterized in the specification. The Examiner notes that the instant claims currently recite the compound of claim 1 and 15 with a laundry list of possible groups or variables and the claims are not a representative of any particular species. Written description issues may also arise if the knowledge and level of skill in the art would not have permitted the ordinary artisan to immediately envisage the claimed product arising from the disclosed process. See, e.g., Fujikawa v. Wattanasin, 93 F.3d 1559, 1571, 39 USPQ2d 1895, 1905 (Fed. Cir. 1996) (a "laundry list" disclosure of every possible moiety does not necessarily constitute a written description of every species in a genus because it would not "reasonably lead" those skilled in the art to any particular species); In re Ruschig, 379 F.2d 990, 995, 154 USPQ 118, 123 (CCPA 1967) (See MPEP 2162.1 (A). The specification does not reasonable convey that the Applicants were in possession of the full scope of the claims at the time of filing.
sufficient relevant identifying characteristics in the way of complete/partial structure or physical and/or chemical properties
A correlation between structure and function, for the instantly claimed genus of compounds, is not disclosed in the specification. The specification does not provide sufficient structure-function features common to the claimed genus that would allow one of ordinary skill in the art to recognize which of the numerous peptides encompassed by the Formula I would possess the recited ability to prevent or treat all cancers and prevent and treat all diseases. The claim recites multiple variables along the residue positions of the cyclic peptide while the biological testing is limited to specific compounds. The instant Examples are focused on producing the compounds and on Kras inhibition. The disclosure of RAS binding or inhibition does not demonstrate possession of the full genus of cyclic peptides have the claimed function of preventing and treating cancer. The deficiency is particularly apparent with respect to preventing all diseases including cancer because the specification does not identify the structural characteristics or experimental evidence demonstrating the broad genus of peptide would possess cancer preventing activity. Importantly, since the claim recites “preventing” the subject by definition may not have a disease or cancer yet. The specification does not sufficiently identify the patient population to whom the peptide would be administered.
Representative number of examples
A “representative number of species” means the species which are adequately described are a representative of the entire genus. Therefore, when there is a substantial variation within a genus, the applicant must describe a sufficient variety of species to reflect the variation within the genus. The disclosure of only one species encompassed within a genus adequately describes a claim directed to that genus only if the disclosure "indicates that the patentee has invented species sufficient to constitute the gen[us]." See Enzo Biochem, 323 F.3d at 966, 63 USPQ2d at 1615; Noelle v. Lederman, 355 F.3d 1343, 1350, 69 USPQ2d 1508, 1514 (Fed. Cir. 2004) (Fed. Cir. 2004) ("[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 MPEP 2163.3 (ii). The elected species and the compounds recited in the application specification are not a representation of the entire genus recited in the claims. The specification fails to provide adequate written description for the genus of compounds claimed 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.
Claims 10-22 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 certain specifically tested cyclic peptide compounds for inhibition of RAS activity, does not reasonably provide enablement for treating or preventing cancer with the peptide of claim 1. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to practice the invention commensurate in scope with these claims.
As stated in MPEP 2164.01(a), “there are many factors to be considered when determining whether there is sufficient evidence to support a determination that a disclosure does not satisfy the enablement requirement and whether any necessary experimentation is “undue.”
The factors to be considered when determining whether a disclosure meets the enablement requirement of 35 USC 112, first paragraph, were described in In re Wands, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988) as:
1. the nature of the invention;
2. the breadth of the claims;
3. the state of the prior art;
4. the relative skill of those in the art;
5. the predictability or unpredictability of the art;
6. the amount of direction or guidance presented [by the inventor];
7. the presence or absence of working examples; and
8. the quantity of experimentation necessary [to make and/or use the invention.
(1) The Nature of the Invention
Claim 10 is drawn to a method for treating or preventing cancer comprising administering to a subject in need thereof the pharmaceutical composition according to claim 1. Claim 15 is drawn to a method of treating or preventing a disease comprising administering a cyclic peptide of Formula I. The peptide of claim 1 and 15 is a large genus of cyclic peptides defined by different amino acid side chains, N-substituents, cyclization/linker groups and further defines the cyclic peptides for the treatment and prevention of any disease and cancer.
(2) The Breadth of the claims
The claims will be given its broadest reasonable interpretation. The applicable rule for interpreting the claims is that “each claim must be separately analyzed and given its broadest reasonable interpretation in light of and consistent with the written description.” See MPEP 2163(II)(1), citing In re Morris, 127 F.3d 1048, 1053-1054; 44 USPQ2d 1023, 1027 (Fed. Cir. 1997). In view of this rule, Claim 10 is drawn to treating and preventing all cancer types with the broad genus of peptides of claim 1 (formula I) and claim 15 is drawn to treatment and prevention of any disease with formula I. The claims are extremely broad encompassing numerous independent alternatives at multiple amino acids along the peptide. The possible combinations encompass a huge genus of distinct peptides. Claims 10-22 are very broad and inclusive of treatment and prevention of all diseases and cancers. The breadth of the claims exacerbates the complex nature of the subject matter to which the present claim is directed. The claims are extremely broad due to the vast number of diseases and cancers known in the art. Different diseases have distinct etiologies and pathologies. For example, cancer is not a single disease, or cluster of closely related disorders. There are hundreds of cancers, which have in common only some loss of controlled cell growth. Cancers are highly heterogeneous at both the molecular and clinical level, something seen especially in, for example, the cancers of the breast, brain and salivary glands. They can occur in pretty much every part of the body. Adding to the breadth of the claims is that the patient population includes subjects that do not yet have cancer due to the limitation “preventing”. The potentially relevant population is extremely broad and encompasses disease free and cancer free subjects.
(3) The state of the prior art and (5) The predictability or unpredictability of the art
Ras inhibitors are known in the art and persons of ordinary skill in the art know the techniques for making and testing them. However, a person of ordinary skill in the art would not be able to make the large genus of compounds and test them for preventing and treating the large genus diseases and cancer types. It would require undue experimentation.
While the state of the art is relatively high with regard to the treatment of specific diseases and cancer types, the state of the art with regard to treating all diseases or cancer or preventing all diseases and cancers is non-existent. Importantly, the prior art is silent regarding treatment or preventing of all diseases or types of cancer with a single peptide. There is no known compound that is able to treat all diseases. There is no known anticancer agent that is effective against all cancer cell types. The cancer treatment art involves a very high level of unpredictability. While the state of the art is relatively high with regard to the treatment of specific cancers with specific agents, it has long been underdeveloped with regard to the treatment of cancers broadly. The lack of significant guidance from the present specification or prior art with regard to the actual treatment of all cancer cells in a mammal, including a human subject, with the claimed active ingredient makes practicing the claimed invention unpredictable. Thus, the specification or the art does not provide enablement for treatment of all diseases or cancers.
For example, there is no known treatment for many diseases. For example, Huntington’s disease is a neurological disease with treatment focuses on lessening some symptoms. The Mayo clinic (Huntington's disease - Diagnosis and treatment - Mayo Clinic> accessed 10/2/26) teaches that no treatments can alter the course of Huntington’s disease. There is no indication that Formula I would be able to treat or prevent Huntington’s disease.
For example, the Merck Manual (<Pancreatic Cancer - Oncology - Merck Manual Professional Edition> accessed 10/2/26) teaches that the prognosis of pancreatic cancer is poor because many patients have advanced disease by the time of diagnosis. The 5 year survival rate is below 5%. There was no teaching that pancreatic cancer is treatable or preventable.
The art is not enabling or treating or preventing all disease or cancers with a single agent. Different types of cancers affect different organs and have different methods of growth a and different vulnerabilities. Therefore, the state of the art at the time of the application is that treatment and prevention of all diseases and cancers is not well understood and therapy is challenging and complex. Adding to the complexity are the many different type of disease and cancer types.
It is noted that pharmaceutical and biological art is generally unpredictable, requiring each embodiment to be individually assessed for physiological activity.
Adding to the unpredictability is that many treatment options may show promise in animal models, but may fail to show therapeutic improvement in clinical trials. There is no absolute predictability, even in view of the high level of skill in the art(4) The relative skill of those in the art
MPEP 2141.03 states (in part)” A person of ordinary skill in the art is also a person of ordinary creativity, not an automaton.” KSR International Co. v. Teleflex Inc., 127 S.Ct. 1727, 167 LEd2d 705, 82 USPQ2d 1385, 1397 (2007). “[I]n many cases a person of ordinary skill will be able to fit the teachings of multiple patents together like pieces of a puzzle.” Id. Office personnel may also take into account “the inferences and creative steps that a person of ordinary skill in the art would employ.” Id. At 1396, 82 USPQ2d at 1396. The “hypothetical person having ordinary skill in the art’ to which the claimed subject matter pertains would, of necessity have the capability of understanding the scientific and engineering principles applicable to the pertinent art.” Ex parte Hiyamizu, 10 USPQ2d 1393, 1394 (Bd. Pat. App. & Inter. 1988) (disagreeing with the examiner’s definition of one of ordinary skill in the art (i.e. a doctorate level engineer or scientist working at least 40 hours per week in semiconductor research or development), and finding that the hypothetical person is not definable by way of credentials, and that the evidence in the application did not support the conclusion that such a person would require a doctorate or equivalent knowledge in science or engineering). In the instant case, the skill in the art high with respect to physicians and scientists. The level of skill in the art (physicians and scientists) would be high.
(6) The amount of direction or guidance presented (by the inventor) and (7) The presence or absence of working examples
The specification contains working examples that support specific compounds for inhibitor of RAS. The specific compounds include 488, 872,1201,2187 and 2188. FIG. 11 shows the amino acid sites where and the extent to which each of the cyclic peptide compounds 488, 872, 1201, 2187, and 2188 interacts with the human Kras G12D mutant. Therefore, the specification supports RAS inhibition with the specific compounds.
In contrast, the applicant provides little in way of direction or guidance regarding treating or preventing all diseases and cancers. There were no examples of treating any disease or cancer. The specification does not provide examples of tumor inhibition or delayed tumor growth. There was no examples of preventing any disease or cancer.
(8) The quantity of experimentation necessary (to make and/or use the invention)
Owing to the factors listed above, especially in points 6 and 7, the amount of experimentation needed will be extensive in view of the lack of guidance by the inventor. MPEP 2164.01(a) states, “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 1557,1562, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993).” That conclusion is clearly justified here.
The instant breadth of the claim is broader than the disclosure, specifically, the instant claims are directed to treating and preventing cancer, but the specification, prior art or instant disclosure does not provide support for this.
In conclusion, the instant application is while being enabling for certain specifically tested cyclic peptide compounds for inhibition of RAS activity, does not reasonably provide enablement for treating or preventing all diseases or cancer with the peptide of Formula (1).
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 10 and 15 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.
Claim 10 recites a method for treating or preventing cancer, comprising administering to a subject in need thereof the pharmaceutical composition according to claim 1. Claim 1 recites a cyclic peptide formula containing many parentheses. It is unclear whether the limitations in the parentheses are a required part of the claimed invention.
Claim 15 recites a method for treating or preventing a disease, comprising administering to a subject in need thereof an effective amount of a cyclic peptide compound represented by formula I. Claim 15 recites a cyclic peptide formula containing many parentheses. It is unclear whether the limitations in the parentheses are a required part of the claimed invention.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 10-22 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-12 of U.S. Patent No. 12,371,454. Although the claims at issue are not identical, they are not patentably distinct from each other because the USPN claims a compound that meets the limitations of Formula I. The USPN claims treatment of pancreatic cancer. Therefore, the USPN anticipates the limitation of the instant claims.
Claims 10-22 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 2-10, 12, 15 and 17-26 of copending Application No. 17/773,733 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the copending application claims a cyclic peptide that is identical to the cyclic peptide instantly claimed. The specification of the copending application teaches some embodiment wherein the invention can be used for treating and preventing cancer [PGPUB3236]. MPEP 804 states: The portion of the specification of the reference that describes subject matter that falls within the scope of a reference claim may be relied upon to properly construe the scope of that claim. In particular, when ascertaining the scope of the reference’s claim(s) to a compound, the examiner should consider the reference’s specification, including all of the compound’s uses that are disclosed. See Sun Pharm. Indus., 611 F.3d at 1386-88, 95 USPQ2d at 1801-02.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Closest Prior art
The closet prior art is Kariyuki et al. (WO2013100132A1). Kariyuki et al. teach a novel method of cyclization of a peptide. In particular, Kariyuki teaches a cyclic peptide with the structure DP-66 (Page 169) as shown below:
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Kariyuki et al. teach a compound that meets the structural limitations of Formula 1. Kariyuki et al. does not teach or suggest the peptide for treatment or preventing a disease or cancer.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to TARA L MARTINEZ whose telephone number is (571)270-1470. The examiner can normally be reached Mon-Fri 8:00-5:00.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Lianko Garyu can be reached at (571)270-7367. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/TARA L MARTINEZ/Primary Examiner, Art Unit 1654
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