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 .
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 03/10/2024 was filed in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
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, 3, 5, 6, 13, 14, 19, 20, 26, 30, 31, 32, 34, 35, 42, 43, 48, 49, 54, and 88 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.
Claim 1 is drawn to a peptidomimetic compound comprising the amino acid sequence of SEQ ID NO: 1 having 0 to 5 conservative amino acid substitutions wherein the compound comprises at least one structural stabilization moiety that links two non-adjacent amino acid residues. Applicant has, however, only disclosed possession of the peptidomimetic compound comprising the sequence according to SEQ ID NO: 1 and the representative stapled peptide (Stp(15,19))H2N-NEDIDQMFSTLLGE(S5)DLL(S5)QS-OH wherein the S5 variables denote the modified amino acid linkers. Given the broad scope of claim 1, particularly with regard to the conservative substitutions of amino acids, a person having ordinary skill in the art would recognize that any chemical structure that can be classified as an amino acid (including unnatural or uncommon amino acids and amino acid residues) that has similar properties to the amino acid that it is replacing can be included, and these structures need not necessarily be present in the prior art. According to the specification, the conservative substitutions must maintain the charge/hydrophobicity of the peptide, but, as explored by Sengupta et al., even peptide modifications with the same charge can substantially affect the structure and function of the peptide via different folding (see page 9942, paragraph 1). As such, it would not be clear to one having ordinary skill in the art that the entire scope of the claim would have the claimed function of the peptide of SEQ ID NO: 1. Further, given that the scope includes chemical structures that are not necessarily present in the prior art, one having ordinary skill in the art would not recognize in applicant’s disclosure a description of the entire scope of the invention defined by the claims. In other words, a broad genus claim is presented but the disclosure only describes a narrow species with no evidence that the genus is meaningfully contemplated. The written description requirement is not necessarily met when the claim language appears in ipsis verbis in the specification. "Even if a claim is supported by the specification, the language of the specification, to the extent possible, must describe the claimed invention so that one skilled in the art can recognize what is claimed. The appearance of mere indistinct words in a specification or a claim, even an original claim, does not necessarily satisfy that requirement" (Enzo Biochem, Inc. v. Gen-Probe, Inc., 323 F.3d 956, 968, 63 USPQ2d 1609, 1616 (Fed. Cir. 2002)). In the instant case, although the specification does mention several examples of unnatural amino acids, including S-pentenylalanine and R-pentenylalanine, the description does not disclose distinct or substantial examples of their incorporation into the peptide. Similarly, with regard to the linker, Applicant names potential embodiments, but Applicant does not provide direction or guidance with regard to experimentation for the entire scope of the claimed embodiments, particularly with respect to the types and locations of potential linkers. More specifically, claim 1 claims a stabilization moiety, but applicant only discloses a small sample of alkyl group moieties, which is only a narrow species of the genus of claimed linkers. Given the very broad nature of the claimed linkers and the lack of working examples of any non-alkyl linker with 5-20 carbon atoms, a person having ordinary skill in the art does not have sufficient working examples to make linkers beyond these and other conventional linkers. Seeing as all of the pending claims of the instant application incorporate the aforementioned limitations of claim 1, the application fails to meet the requirements of written description for claims 1, 3, 5, 6, 13, 14, 19, 20, 26, 30, 31, 32, 34, 35, 42, 43, 48, 49, 54, and 88. The instant application fulfills the requirements of written description for the peptide of SEQ ID NO: 1 and the representative stapled peptide (Stp(15,19))H2N-NEDIDQMFSTLLGE(S5)DLL(S5)QS-OH according to Figure 7, and it is advised that Applicant amend the claims to reflect the species that fulfill this requirement.
Claims 1, 3, 5, 6, 13, 14, 19, 20, 26, 30, 31, 32, 34, 35, 42, 43, 48, 49, 54, and 88 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 representative stapled peptide (Stp(15,19))H2N-NEDIDQMFSTLLGE(S5)DLL(S5)QS-OH and SEQ ID NO: 1, does not reasonably provide enablement for any peptidomimetic compound comprising the amino acid sequence of SEQ ID NO: 1 having 1 to 5 amino acid substitutions or any linker between two non-adjacent amino acid residues. 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 or use the invention commensurate in scope with these claims.
In order to determine compliance with the enablement requirement of 35 U.S.C. 112(a), the Federal Circuit developed a framework of factors in In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988), referred to as the Wands factors to assess whether any necessary experimentation required by the specification is "reasonable" or is "undue." Consistent with Amgen Inc. et al. v. Sanofi et al., 598 U.S. 594, 2023 USPQ2d 602 (2023), the Wands factors continue to provide a framework for assessing enablement in a utility application or patent, regardless of technology area. See Guidelines for Assessing Enablement in Utility Applications and Patents in View of the Supreme Court Decision in Amgen Inc. et al. v. Sanofi et al., 89 FR 1563 (January 10, 2024). These factors include, but are not limited to:
(A) The breadth of the claims;
(B) The nature of the invention;
(C) The state of the prior art;
(D) The level of one of ordinary skill;
(E) The level of predictability in the art;
(F) The amount of direction provided by the inventor;
(G) The existence of working examples; and
(H) The quantity of experimentation needed to make or use the invention based on the content of the disclosure.
With regard to the breadth of the claims and the level of ordinary skill, claim 1 is drawn to a peptidomimetic compound comprising the amino acid sequence of SEQ ID NO: 1 having 0 to 5 conservative amino acid substitutions wherein the compound comprises at least one structural stabilization moiety that links two non-adjacent amino acid residues. Given that, as claimed, the peptidomimetic compound can contain any conservative amino acid substitution, including unnatural amino acids, the breadth of the claim is broad and includes any structure under the class of amino acids that reasonably has similar properties like structure, size, and charge as compared to those claimed. Here, the Federal Circuit, citing McRO, provides guidance on the application of enablement to genus claims, holding that "[a]lthough a specification does not need to describe how to make and use every possible variant of the claimed invention, when a range is claimed, there must be reasonable enablement of the scope of the range." The propriety of a rejection based upon the scope of a claim relative to the scope of the enablement concerns (1) how broad the claim is with respect to the disclosure and (2) whether one skilled in the art could make and use the entire scope of the claimed invention without undue experimentation. Given the broad bounds and lack of a representative amount of working examples with regard to the amino acid structures that can be included, one having ordinary skill in the art would not reasonably be enabled to make and use all of the compounds claimed within the breadth of claim 1, particularly considering the amount of experimentation necessary when using unnatural or uncommon amino acids or residues thereof. Moreover, as discussed above, according to Sengupta et al., even peptide modifications with the same charge can substantially affect the structure and function of the peptide (see page 9942, paragraph 1). A person having ordinary skill in the art would not recognize which forms of the peptide maintain the function, as it is recognized that even conservative amino acid substitutions can change structure and function, and, thereby, they are not enabled to use the entire scope of the claimed peptides. Similarly, with regard to the linker, Applicant names potential embodiments, but the breadth of claim 1 is very broad and includes any chemical structure that can bind to two non-adjacent amino acids. Claim 1 claims a stabilization moiety, but applicant only discloses a small sample of alkyl group moieties, which is only a narrow species of the genus of claimed linkers. Given the very broad nature of the claimed linkers and the potential structural changes that the claimed linkers can impart, a person having ordinary skill in the art would not be enabled to use the peptide with the entire genus of linkers as claimed.
With regard to the nature of the invention and the level of predictability in the art, the invention claimed in claim 1 is a chemical compound in the form of a peptide with high variability in function given changes in structure. As discussed above, according to Sengupta et al., even peptide modifications with the same charge can substantially affect the structure and function of the peptide (see page 9942, paragraph 1). Here, a person having ordinary skill in the art would not be able to predict the forms of the peptide that have the claimed function, and it would require undue experimentation given the variability in structure/function and the number of chemical compounds that can be included via the substitutions. The nature of the invention and the breadth of claim 1, as discussed above, entails the aforementioned broad bounds of the chemical compounds that can be included via the conservative substitutions of amino acids, particularly considering the potential inclusion of unnatural amino acids or residues thereof, which fall within the nature of the invention as a chemical compound. In other words, it is broad and unpredictable what chemical compounds, unnatural amino acids, or residues may be included on account of the nature of the invention, and one having ordinary skill in the art would not be enabled to use the entire scope of the invention. Similarly, with regard to the linker, Applicant names potential embodiments, but the given the nature of the linkers as chemical compounds, any chemical structure that can bind two non-adjacent amino acids is included in the scope of the claim. Given this nature, a person having ordinary skill in the art would not be able to predict which linker structures maintain the structure and function of the peptide, and would thereby not be enable to use the entire scope of the linkers.
With regard to the existence of working examples, the amount of direction given by Applicant, and the state of the prior art, Applicant has only disclosed possession of the peptidomimetic compound comprising the sequence according to SEQ ID NO: 1. Applicant disclosed the representative stapled peptide (Stp(15,19))H2N-NEDIDQMFSTLLGE(S5)DLL(S5)QS-OH wherein the S5 variables denote the modified amino acid linkers. As such, Applicant has only disclosed the potential functional role of the aforementioned peptidomimetic, and one having ordinary skill in the art would not reasonably be able to make or use any peptidomimetic compound comprising the amino acid sequence of SEQ ID NO: 1 having 1 to 5 amino acid substitutions or any linker between two non-adjacent amino acid residues. Given that Applicant has not disclosed or recited any embodiments beyond the aforementioned representative stapled peptide and SEQ ID NO: 1, a person having ordinary skill in the art would not reasonably find success in making or using other embodiments, as Applicant has not demonstrated how to make or use any of these embodiments. Further, with regard to the quantity of experimentation needed to make or use the invention based on the content of the disclosure, an Applicant motivated to use conservative amino acid substitutions, particularly with regard to unnatural or uncommon amino acids, would not find content in the disclosure that meaningfully directs or informs experimentation for the entire scope of the claimed embodiments beyond those discussed above. Again, given the teaching by Sengupta et al., a person having ordinary skill would not be able to predict which amino acid substitutions would maintain the function of the peptide, and, thereby, they are not enabled to use the peptide as claimed. Similarly, with regard to the linker, Applicant names potential embodiments, but Applicant does not provide direction or guidance with regard to experimentation for the entire scope of the claimed embodiments, particularly with respect to the types and locations of potential linkers. More specifically, claim 1 claims a stabilization moiety, but applicant only discloses a small sample of alkyl group moieties, which is only a narrow species of the genus of claimed linkers. Given the very broad nature of the claimed linkers and the lack of working examples of any non-alkyl linker with 5-20 carbon atoms, a person having ordinary skill in the art does not have sufficient working examples to make linkers beyond these and other conventional linkers. Seeing as all of the pending claims of the instant application incorporate the aforementioned limitations of claim 1, the instant application fails to enable the scope of the invention for claims 1, 3, 5, 6, 13, 14, 19, 20, 26, 30, 31, 32, 34, 35, 42, 43, 48, 49, 54, and 88. The instant application enables a person having ordinary skill in the art to make and use the peptide of SEQ ID NO: 1 and the representative stapled peptide (Stp(15,19))H2N-NEDIDQMFSTLLGE(S5)DLL(S5)QS-OH according to Figure 7, and it is advised that Applicant amend the claims to reflect the species that fulfill the enablement requirement.
Claims 30, 31, 32, 34, 35, 42, 43, 48, 49, and 54 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 ameliorating integrin-related disorders, does not reasonably provide enablement for preventing integrin-related disorders. 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.
In order to determine compliance with the enablement requirement of 35 U.S.C. 112(a), the Federal Circuit developed a framework of factors in In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988), referred to as the Wands factors to assess whether any necessary experimentation required by the specification is "reasonable" or is "undue." Consistent with Amgen Inc. et al. v. Sanofi et al., 598 U.S. 594, 2023 USPQ2d 602 (2023), the Wands factors continue to provide a framework for assessing enablement in a utility application or patent, regardless of technology area. See Guidelines for Assessing Enablement in Utility Applications and Patents in View of the Supreme Court Decision in Amgen Inc. et al. v. Sanofi et al., 89 FR 1563 (January 10, 2024). These factors include, but are not limited to:
(A) The breadth of the claims;
(B) The nature of the invention;
(C) The state of the prior art;
(D) The level of one of ordinary skill;
(E) The level of predictability in the art;
(F) The amount of direction provided by the inventor;
(G) The existence of working examples; and
(H) The quantity of experimentation needed to make or use the invention based on the content of the disclosure.
Claims 30, 31, 32, 34, 35, 42, 43, 48, 49, and 54 are drawn to a method of treating a subject having an integrin-related disorder, including cardiovascular disease and cancer. As defined by the specification, “treating” can mean “preventing” the disease.
With regard to the breadth of the claims, the nature of the invention, and the state of the prior art, the claims are broad and include methods of preventing cancer and cardiovascular disease, the nature of the invention is a peptidomimetic compound used to treat or prevent disease, and there are no recognized means of preventing cardiovascular disease or cancer in the prior art. Given the fact that the breadth of the claims includes preventing diseases, particularly cancer and cardiovascular disease, that the prior art has no recognized means of preventing, a person having ordinary skill in the art would not be enabled to use a method of preventing the aforementioned diseases. This is because this is not recognized as possible in the current state of the prior art. Similarly, with regard to the level of one of ordinary skill in the art and the level of predictability in the art, the structures and functions of peptidomimetic compounds are unpredictable, and one having ordinary skill in the art would not have the skill to make or use the claimed method of preventing cancer because this is not recognized as possible in the art. With regard to the amount of direction provided by the inventor, the existence of working examples, and the quantity of experimentation needed to make or use the invention based on the disclosure, the specification does not describe directions or examples of complete prevention of cancer or cardiovascular disease so as to convey that a person having ordinary skill in the art would be enabled to prevent these diseases via the claimed method. Similarly, given the state of the art and the lack of direction to enable one of ordinary skill in the art to prevent cancers or cardiovascular disease, a significant and undue amount of experimentation would be necessary to achieve this method of prevention, particularly considering that it is not recognized as possible in the state of the art.
Allowable Subject Matter
No prior art reads on the peptidomimetic compound of claims 1, 3, 5, 6, 13, 14, 19, 20, 26, 30, 31, 32, 34, 35, 42, 43, 48, 49, 54, and 88 as written in SEQ ID NO: 1 and the representative stapled peptide (Stp(15,19))H2N-NEDIDQMFSTLLGE(S5)DLL(S5)QS-OH according to Figure 7.
Summary
Claims 1, 3, 5, 6, 13, 14, 19, 20, 26, 30, 31, 32, 34, 35, 42, 43, 48, 49, 54, and 88 are rejected under 35 U.S.C. 112(a) on the grounds of written description and enablement.
Conclusion
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/BRENDAN P. OLISS/Examiner, Art Unit 1658
/LIANKO G GARYU/Supervisory Patent Examiner, Art Unit 1654