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 .
DETAILED ACTION
The amendment to the claims filed after non-final office action on December 2, 2025 is acknowledged. Claims 29, 34, 36, 38, 40 were amended, claims 1-28, 30-33, 35, 37, 39 and 41-47 were canceled and claims 29, 34, 36, 38, 40 are pending in the instant application. The restriction was deemed proper and made final previous office action.
Claims 29, 34, 36, 38, 40 are examined on the merits of this office action.
*Please note that a second Non-final follows as a new Double Patenting rejection is presented below that was filed after the last office action was mailed out.
Withdrawn Rejections/Objections
The rejection of claim(s) 29, 34, 36-38, 40 under 35 U.S.C. 103 as being unpatentable over Peri (US20050059605 A1, cited in Applicant’s IDS) in view of Tseng (Proc. Natl. Acad. Sci. USA Vol. 90, pp. 1992-1996, March 1993, cited previously) is hereby withdrawn in view of cancelation of claim 37 in the amendment filed 12/2/2025.
The objection to claim 37 is hereby withdrawn in view of cancelation of claim 37 in the amendment filed 12/2/2025.
Maintained/Revised Rejections
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 USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The 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/process/file/efs/guidance/eTD-info-I.jsp.
Claims 29, 34, 36, 38, 40 remain rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-18 of U.S. Patent No. 10968266 B2. Although the claims at issue are not identical, they are not patentably distinct from each other because:
The instant application claims: A peptide selected from the group consisting of: a peptide consisting of 28 contiguous amino acids of sequence (SEQ ID NO: 74),a peptide consisting of 27 contiguous amino acids of sequence (SEQ ID NO: 75),
a peptide consisting of 26 contiguous amino acids of sequence (SEQ ID NO: 76),
wherein X0a is D or E, X0b is K, A, H, R, X1 is H, A, K, F, Y and X2 is K, H or A, and a variant of any of the above peptides having one or two substitutions outside of X0a, X0b, X1 and X2…, wherein said peptide or variant thereof is an antagonist of a GIP receptor (GIPR), with the proviso that said peptide or variant thereof does not have 100% sequence identity to native hGIP3-30 (SEQ ID NO: 1), to native hGIP4-30 (SEQ ID NO: 77) or to native hGIP5-30 (SEQ ID NO: 78)” (instant claim 29). The instant application further claims n/c- terminal acetylation or amidation (claim 29); SEQ ID NO:74 or 11 or variants thereof (see claim 38). The instant application claims variants of SEQ ID NO:11 (claims 37-38) with one to two substitutions and variants of SEQ ID NO:79 (which is human GIP3-30 with substitution at H18A).
Us Patent no ‘10968266 B2 claims a method of using a peptide consisting of 28 contiguous amino acids of SEQ ID NO:74 (which is identical to instant SEQ ID NO:74) (see claim 1); c-terminal amidation or N-terminal acetylated (see claim 5) and variants thereof that encompass non-human GIP3-30. Claim 4 claims SEQ ID NO:81 that is identical to instant SEQ ID NO:81.
Response to Applicant’s Arguments
Applicant requests that any rejection on the grounds of non-statutory obviousness-type double patenting be held in abeyance. Thus, the rejection is maintained.
Claims 29, 34, 36, 38, 40 are/remain provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-16 of US Patent No. 12187773 (previously indicated as US 17/298444). Although the claims at issue are not identical, they are not patentably distinct from each other because:
The instant application claims: A peptide selected from the group consisting of: a peptide consisting of 28 contiguous amino acids of sequence (SEQ ID NO: 74),a peptide consisting of 27 contiguous amino acids of sequence (SEQ ID NO: 75),
a peptide consisting of 26 contiguous amino acids of sequence (SEQ ID NO: 76),
wherein X0a is D or E, X0b is K, A, H, R, X1 is H, A, K, F, Y and X2 is K, H or A, and a variant of any of the above peptides having one or two substitutions outside of X0a, X0b, X1 and X2…, wherein said peptide or variant thereof is an antagonist of a GIP receptor (GIPR), with the proviso that said peptide or variant thereof does not have 100% sequence identity to native hGIP3-30 (SEQ ID NO: 1), to native hGIP4-30 (SEQ ID NO: 77) or to native hGIP5-30 (SEQ ID NO: 78)” (instant claim 29). The instant application further claims n/c- terminal acetylation or amidation (claim 29); SEQ ID NO:74 or 11 or variants thereof (see claim 38). The instant application claims variants of SEQ ID NO:11 (claims 37-38) with one to two substitutions and variants of SEQ ID NO:79 (which is human GIP3-30 with substitution at H18A).
US Patent No. ‘773 claims a GIP analogue of SEQ ID NO:1 which is comprises instant SEQ ID NO:74 wherein X0A is D, Xob is R, X1 is K or Orn, X2 is X3 (which is R or E) which meets the limitations of a variant of SEQ ID NO:74 with one substitution and not 100% sequence identity to human GIP3-30. Regarding instant claims 36, 38, SEQ ID NO:1 of US patent NO. ‘773 meets the limitations of instant SEQ ID NO:11 with two substitutions. Regarding instant claim 40, SEQ ID NO:1 of US Patent NO. ‘773 meets the limitations of a variant of SEQ ID NO:80 with two substitutions.
Response to Applicant’s Arguments
Applicant requests that any rejection on the grounds of non-statutory obviousness-type double patenting be held in abeyance. Thus, the rejection is maintained.
Claims 29, 34, 36, 38, 40 are/remain provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-23 of co-pending 16/617698 (Now US Patent 11572399). Although the claims at issue are not identical, they are not patentably distinct from each other because:
The instant application claims: A peptide selected from the group consisting of: a peptide consisting of 28 contiguous amino acids of sequence (SEQ ID NO: 74),a peptide consisting of 27 contiguous amino acids of sequence (SEQ ID NO: 75),
a peptide consisting of 26 contiguous amino acids of sequence (SEQ ID NO: 76),
wherein X0a is D or E, X0b is K, A, H, R, X1 is H, A, K, F, Y and X2 is K, H or A, and a variant of any of the above peptides having one or two substitutions outside of X0a, X0b, X1 and X2…, wherein said peptide or variant thereof is an antagonist of a GIP receptor (GIPR), with the proviso that said peptide or variant thereof does not have 100% sequence identity to native hGIP3-30 (SEQ ID NO: 1), to native hGIP4-30 (SEQ ID NO: 77) or to native hGIP5-30 (SEQ ID NO: 78)” (instant claim 29). The instant application further claims n/c- terminal acetylation or amidation (claim 29); SEQ ID NO:74 or 11 or variants thereof (see claim 38). The instant application claims variants of SEQ ID NO:11 (claims 37-38) with one to two substitutions and variants of SEQ ID NO:79 (which is human GIP3-30 with substitution at H18A).
US Patent NO. 11572399 claims a GIP analogue consisting of hGIP3-30 and variants thereof with 1-6 amino acid substitutions meeting the limitation of instants claims 29, 34, 36, 38, 40 (see claim 1 of US Patent NO. ‘399). US Patent NO. 11572399 further claims wherein Xoa is D, Xob is K and X1 is H and X2 is K thus meeting the limitations of instant claim 29 (see claim 19 for example) and C-terminal amidation (see claim 20). US Patent NO. 11572399 claims SEQ ID NO:81 which is identical to instant SEQ ID NO:81 of claim 40. Regarding claims 36, 38, US Patent NO. 11572399 claims hGIP3-30 with one to two substitutions meeting the limitations of a variant of instant SEQ ID NO:11 with 1 to 2 substitutions. Claims 1-23 are anticipatory of over instant claims 29, 34, 36, 38, 40.
Response to Applicant’s Arguments
Applicant requests that any rejection on the grounds of non-statutory obviousness-type double patenting be held in abeyance. Thus, the rejection is maintained.
Claim Rejections – 35 USC § 112, first paragraph
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 29, 34, 36, 38, 40 are/remain 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 § 2163 states that the written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, 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.
Scope of the claims
The claims are drawn “A peptide selected from the group consisting of: a peptide having an amino acid sequence consisting of 28 contiguous amino acids of sequence EGTFISDYSIAMXoaXobIX1QQDFVNWLLAQX2 (GIP3 -30; SEQ ID NO: 74), a peptide consisting of 27 contiguous amino acids of SEQ ID NO:75, a peptide consisting of 26 contiguous amino acids of SEQ ID NO:76 (GIP4-30; SEQ ID NO: 75), wherein X0a is E or E, X0b is K, A, H, R, X1 is H, A, K, F, Y and X2 is K, H, A and…..a variant of any one of the above peptide with one to two substitutions introduced at positions outside amino acids X0a, X0b, x1 and X2, wherein the substitutions are select from…see page 3 of amended claim, wherein said peptide or variant is an antagonist of GIPR, with the proviso that the peptide or variant does not have 100% sequence identity to native SEQ ID NO:1, 77 or 78”. Applicants additionally recite a long list of possible substitutions organized by chemical class (polar, non polar, aromatic, acidic basic etc…) which in effect allows 1-2 substitutions at any position other than Xoa, Xob, X1 or X2. Thus, the scope of the claims encompasses a genus of a vast number of peptides differing by one or two residues from the parent in addition to the variables of Xoa, Xob, X1 and X2.
Therefore, to meet the written description requirement of 35 U.S.C. § 112, first paragraph, the specification must disclose a representative number of species that meet both the structural and functional limitations of the genus or the specification and/or the prior art must identify the structural elements that correlate to the claimed function in a manner that demonstrates to one of ordinary skill in the art that Applicant was in possession of the claimed genus at the time the application was filed.
Actual Reduction to Practice
MPEP § 2163 states that the written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice. A “representative number of species” means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus.
In the instant case, Applicants reduce to practice the following: native hGIP3-30, variants at position 18 (H18-R, A, K); variants at position 15 (Asp15, E or N) and double mutants (15E18A, 16A18A); some truncations (1-30, 2-30, 4-30, 5-30). Example 8 provides experimental binding data for a handful of mutants. The double mutant 15E18A shows an improved Ki whereas the 18R30R shows diminished potency. No variants are disclosed at the defined X positions, nor at most other residues in the 26-28mer peptide.
Interestingly, studies looking at the mutations at positions 18 and 15 showed variability in the Ki values (the ability to be an antagonist). As stated above, Some mutations increased Ki while others decreased. Importantly, no studies were done with variants with substitutions outside of positions 15-16, 18 or 30. It was stated that In vivo studies were only performed with hGIP(3-30) (see Example 9) however, no data was provided. Thus, there are no examples provided regarding actually treating any metabolic disorder with any peptide (the intended use and purpose). The possibilities are vast and Applicants provide little guidance as to which variants would have the desired functional properties. Variants with one or two mutations with arginine are not sufficient examples given the breadth of the genus. There are no examples with regards to the peptide variants of the instant claims and the ability to have the properties in claim 29 and the intended utility of the peptides.
Therefore, the instant specification has failed to meet the written description requirement by actual reduction to practice of a representative number of species alone.
Sufficient relevant identifying characteristic
Applicants rely on the broad listing of chemical substitution classes to suggest possession of the claimed genus. However, boilerplate recitations of conservative substitutions are insufficient to meet the written description requirement. Such lists describe what could be done, but not demonstrate that applicants had possession of the specific variants now encompassed by the claims. Here, the actual data show that even substitutions at the same position yield unpredictable results. His18 to Arg maintained activity while His18 to Arg and His18 to Lys reduced potency. Similarly, double mutants showed divergent outcomes, with 15E18A unexpectedly improving potency while 18R30R impaired it. These results highlight that activity cannot be reliably predicted across substitutions, undermining the sufficiency of generic substitutions listings.
Complete structure
As stated above, the human GIP (3-30), 4-30 and 5-30 and truncated variants are described. No variants were actually reduced to practice with regards to the intended utility.
Partial structure:
This level of structural description is insufficient to define the instantly claimed genus which requires the property being a GIPR antagonist. The number of possible peptides encompassed by the genus is vast and the specification is lack of specific guidance regarding variants of SEQ ID NOs:74-76 and therefore further contributes to the unpredictability in the art.
Although one of ordinary skill in the art could determine if a given amino acid sequence meets the structural requirements of the genus, given the breadth of the genus and the number of possible peptide peptides and lack of guidance within the specification, it would not be possible to determine from the sequence alone if the protein is able to have the GIP inhibiting properties/antagonist activity as recited in claim 29.
Physical and/or chemical properties:
The specification provides amino acid sequences but does not disclose meaningful physical or chemical properties for the claimed variants, beyond limited Ki values for a few mutants. No stability, solubility, half life or secondary structural data are given across the genus. Without such information, there are insufficient physical/chemical identifiers linking claimed sequence variations to functional peptides.
Functional characteristics when coupled with a known or disclosed correlation between function and structure:
The specification does not describe a general correlation between structure and function for the claimed genus. The role of the specific amino acids of the GIP fragments regarding treatment of metabolic disease and having GIP inhibitory properties/GIPR antagonism is unknown. As a result, it is impossible to predict, based on the specification, how changing any amino acid position will affect the ability of the instant peptides to treat metabolic diseases. Gault (cited previously) teaches how a single substitution at position 3 of GIP had varying activities on the GIP analogue. Gault teaches that “In the present study, five Glu3-substituted analogues of GIP, namely (Ala3)GIP, (Lys3)GIP, (Phe3)GIP,(Trp3)GIP and (Tyr3)GIP, were synthesized and tested for DPP-IV resistance and biological activity both in vitro and in vivo. The properties of these analogues were compared with native GIP and (Pro3)GIP. Substituting the native Glu3 with an Ala, Phe, Trp or Tyr residue resulted in analogues with DPP-IV degradation profiles and half-lives similar to the native peptide, thereby imply-ing that these residues were still capable of fulfilling the strict substrate specificity required for DPP-IV action. In contrast, substituting Glu3 with a Lys residue resulted in an analogue that displayed weakly improved enzyme stability compared to native GIP. “Of the analogues tested only (Ala3)GIP, elicited a significantly enhanced (1.7-fold;p< 0.001) insulin response compared with control. (Lys3)-GIP, (Phe3)GIP, (Trp3)GIP, (Tyr3)GIP and (Pro3)GIP displayed significantly reduced insulinotropic activity(p< 0.05 top< 0.001) compared with native GIP (Fig. 3;Table 3)” (See page 266, right hand column, “in vitro insulin secretion”). Gault further teaches that “Of the analogues tested, (Ala3)GIP, (Phe3)GIP and (Tyr3)GIP demonstrated significant GIP-R antagonist activity in ob/obmice. Their inhibitory actions though were much less pronounced than the already well-established GIP-R antagonist, (Pro3)GIP, which has the additional benefit of being completely resistant to the actions of DPP-IV” (see page 273, left hand column, last paragraph). Thus, clearly a single mutation in GIP can have a dramatic effect on the peptides function (agonist vs. antagonist) and even within that group (agonist or antagonist) different activities on insulin and glucose. These teachings further provide evidence that even single substitution can have a dramatic effect on GIP and the properties of the GIP analogue.
Applicants assert that all claimed variants act as GIP receptor antagonists. However, the experimental data in Example 8 contradicts a simple structure function correlation. Substitutions at the same site lead to markedly different effects on antagonist potency. Applicants provide no unifying principle or predictive correlation that would allow a person of ordinary skill to extrapolate form the limited examples at positions 15-18 and 30 to substitutions at all possible residues (including the X variable positions0. Without such a principle, a person of ordinary skill in the art could not reasonably conclude that the entire genus of one or two substitution variants will retain the claimed function.
Method of Making
Applicants disclose making SEQ ID Nos:74-76 and specific truncated fragments thereof. Where the specification fails to provide description is in the structure of the peptides variants of SEQ ID Nos:74-76 (and GIP 3-30, 4-30 and 5-30). For all of the reasons presented above, one of ordinary skill in the art would not know which of the countless proteins that meet the structural requirements of the claims would have the desired functional properties.
Standard peptide synthesis and recombinant expression methods are described, but these are routine in the art and merely enable production of peptides once their sequences are known. They do not establish that applicants were in possession of the full breadth of the claimed genus.
Conclusion
In conclusion, only sequences reduced to practice and listed specifically in the claims satisfy the written description requirements of 35 U.S.C. 112, first paragraph.
Response to Applicant’s Arguments
Applicant respectfully disagrees. It is well settled that an applicant needs not provide an ipsis verbis description for the claimed invention. In re Gosteli, 2 F.2d 1008, 1012, 10 USPQ2d 1614, 1618 (Fed. Cir. 1989) (stating that the written description requirement does not require an applicant to "describe exactly the subject matter claimed, [instead] the description must clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed" (citations omitted)). The Federal Circuit emphasized that the descriptive text needed to meet the written description requirement "varies with the nature and scope of the invention at issue, and with the scientific and technologic knowledge already in existence." Capon v. Eshhar, 418 F.3d 1349, 1357 (Fed. Cir. 2005). Further, information which is well known in the art need not be described in detail in the specification. See, e.g., Hybritech, Inc. v. Monoclonal Antibodies, Inc., 802 F.2d 1367, 1379-80,231 USPQ 81,90 (Fed. Cir. 1986)."
In the present application, it is respectfully submitted that Applicant was in possession of the full scope of the claimed subject matter as demonstrated in the specification and thus the claims do not lack written description. As an initial matter, regarding the "Scope of the claims," claim 29 has been amended as specified above, to clarify that Xoa, Xob, Xi and X2 are as defined in claim 29, as also in the variants.
Moreover, claim 29 defines variants of claimed peptides, wherein the amino acid sequence of the variant differs from SEQ ID NO: 74, SEQ ID NO: 75 or SEQ ID NO: 76, in that the amino acid sequence of the variant comprises one or two amino acid (at positions other than Xoa, Xob, Xi and X2), which cannot be any substitutions, but can only be as specified below and in claim 29 (i-xiii). As provided in the application, for example, on page 9, lines 9-25, the above listed possible substitutions are substitutions of an amino acid residue for an "equivalent amino acid residue", which is an amino acid residue capable of replacing another amino acid residue in a polypeptide without substantially altering the structure and/or functionality of the polypeptide. Equivalent amino acids thus have similar properties such as bulkiness of the side-chain, side chain polarity (polar or non-polar), hydrophobicity (hydrophobic or hydrophilic), pH (acidic, neutral or basic) and side chain organization of carbon molecules (aromatic/aliphatic).
Hence, while claim 29 allows for 1 or 2 substitutions at 22 to 24 positions, each of these 1 or 2 amino acid substitutions can only be selected from the above listed possibilities, which are not "vast" or "countless" as asserted by the Office Action but rather limited, depending on which amino acid is to be substituted, and which are known to preserve function and structure of the peptides. Moreover, only the variants with substitutions at positions 15, 16, 18 and 30 include the possibility of substituting with non-equivalent amino acid residues, and only because the data in the application as filed confirmed that the substituted peptides preserve GIPR antagonist. While some variation in Ki is observed, antagonism for GIPR is indeed present. Taken together, Applicant submits that all claimed variants, components, and constituents of the recited SEQ ID NOs are supported in the specification because they are defined by structure and function to a finite scope of the claimed subject matter which is fully supported by the description of the recited SEQ ID NOs provided in the specification, e.g. in the structure of SEQ ID NOs, and the specification description of each of the components and constituents of SEQ ID NOs. Regarding the functionality and utility of the claimed peptide, the Office Action alleges that "no variants were actually reduced to practice with regards to the intended utility." Office Action, para. 4 of p. 4, Applicant respectfully disagrees with this allegation, submitting that Applicant has provided several working examples of peptides which clearly demonstrate that Applicant was in possession of the full scope of the claimed subject matter as demonstrated in the specification and thus the claims do not lack written description. In particular, Applicant refers the Examiner's attention to Example 8 and Figures 13-15 of the application as filed, where Applicant provides functional data confirming that variants carrying the following non-naturally occurring amino acid substitutions are antagonists of GIPR: H18A, H18K, D15E, H18A, K16A. As paragraph bridging pages 3-4, the Office Action further alleges that "there are no examples with regards to the peptide variants of the instant claims and the ability to have the properties in claim 29." Applicant respectfully disagrees with this allegation, submitting that the application as filed provides several examples of functionality of the claimed peptides and variants, see for example Tables 1, 2A, 2B, 2C, Example 7, and Example 8. Moreover, additional specific amino acid substitutions are suggested on page 71 of the application as filed, in particular D15N, K16H, K16R, H18F, H18W, K30R, and K30H. Accordingly, the Office Action's allegation that "there are no examples with regards to the peptide variants of the instant claims and the ability to have the properties in claim 29" is incorrect.
Response to Applicant’s Arguments
Applicant’s arguments have been fully considered but not found persuasive. While the specification discloses certain variants at positions 15 and 18, the claims encompass a significantly broader genus, including variability at positions 15-16, 18 and 30 (X0a, X0b, X1, X2), as well as peptides containing one or two substitutions at positions outside these defined residues. The specification does not provide any working examples of substitutions at positions 16 or 30, any examples combining substitutions across all claimed variable positions or any examples of substitutions at positions outside the defined X positions. Where, as here, a claimed genus encompasses substantial structural variation, the written description requirement is satisfied only by disclosure of a representative number of species reflecting the full scope of that variation. See MPEP2163. The limited number of disclosed variants, confined primarily to positions 15 and 18, does not reasonably demonstrate possession of the full claimed genus.
Applicant further relies on the disclosure of conservative substitutions classes to support the breadth of the claimed genus. However, generic recitations of possible substitutions do not alone demonstrate possession of a claimed genus. Such disclosures merely described what could be substituted rather than what Applicant has possession of. Moreover, the experimental data provided in the specification demonstrates that substitutions, even at the same position, result in divergent and unpredictable functional outcomes. For example, substitutions at a single residue position yield differing effects on antagonist activity, and double mutants exhibit inconsistent results. These findings undermine any assertion that conservative substitutions are predictable in this peptide. Accordingly, the disclosure of substitutions classes does not provide sufficient written description support for the full scope of the claimed genus.
Applicant further argues that the claimed peptides are defined by their function as a GIP receptor antagonist, and that the specification supports this functional limitation. This argument is not persuasive. Functional claim limitations may, in certain circumstances, support a genus inf the specification either discloses a representative number of species exhibiting the claimed function or provides a structural function correlation that allows on of ordinary skill in the art to predict which members of the genus will possess the claimed activity. Neither condition is met here. The specification provides experimental data for only a limited number of peptide variants. Further, the data demonstrate that even minor sequence variation can result in significant and unpredictable changes in activity. The specification does not identify any structural features or motifs that reliably correlate with GIPR antagonism across the claimed genus. Accordingly, one of ordinary skill in the art would not be able to determine, based on the disclosure, which peptides within the claimed genus would possess the required antagonist activity.
Applicant argues that the claimed peptides are structurally defined by a core sequence with limited variability at positions 15-16, 18 and 30. This argument is not persuasive. Although the claims recite a core sequence with defined variable positions, the scope the claims is not limited to substitutions at positions outside the defined X positions. The specification provides no guidance as to which of these additional positions may be modified without loos of function, nor does it provide examples of such substitutions. In view of the demonstrated unpredictability of amino acid substitutions in the disclosed system, the absence of such guidance is significant.
Applicant asserts that routine peptide synthesis methods enable a skilled artisan to make and test the claimed peptides. This argument is not persuasive because it addresses enablement rather than written description. The issue is not whether one of ordinary skill in the art could make and test the claimed peptides, but whether the specification demonstrates that Applicant was in possession of the claimed genus at the time of filing. The ability to synthesize peptides and evaluate their activity does not establish that Applicant had possession of the full scope of the claimed genus, particularly where the genus encompasses a large number of structurally diverse peptides with unpredictable functional properties.
Applicant relies on experimental data (example 8) to demonstrate that variants retain antagonist activity. This argument is not persuasive. While the specification provides data for a limited number of variants, the results demonstrate that substitutions can have widely varying effects on activity. In some cases, substitutions improve activity, while in others they diminish it. Even substitutions at the same position yield inconsistent outcomes. These results indicate that the relationship between sequence and function is not predictable. As such, the data provided do not support the conclusion that the full scope of the claimed genus will possess the claimed antagonists activity.
For the reasons set forth above, the specification does not demonstrate possession of the full scope of the claimed genus. The claims encompass a broad range of peptide variants, including substitutions at multiple defined and undefined positions, without sufficient representative examples or a predictive structure function relationship.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 40 is/remains rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 29 recites peptides of SEQ ID Nos:74-76 and functional variants thereof that differ from the recited sequences by only one or two amino acid substitutions outside of X0a, Xob, X1 and X2. Claim 40 claims “The peptide according to claim 29 wherein said peptide is selected from SEQ ID Nos:79-91 and a functional variant of any one of the above peptides, wherein the amino acid sequence of the functional variant differs from SEQ ID NO: 79 to SEQ ID NO: 91 in that the amino acid sequence of the variant comprises one or two amino acid substitutions, wherein said peptide or functional variant thereof is an antagonist of a GIP receptor (GIPR).” Claim 29 requires that any amino acid substitutions occur outside positions X0a, Xob, X1 and X2; however, claim 40 recites a functional variant comprising one or two substitutions without including this limitation. As such, claim 40 encompasses substitutions at positions excluded by claim 29 and therefore broadens, rather than narrows the scope of the base claim.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Response to Applicant’s Arguments
Applicant argues “Without acquiescing to the Office Action's characterization of the claim, Applicant has amended claim 40 as indicated above. In particular, amended claim 40 depends on claim 29 and further limits the subject matter thereof. In view of this amendment, Applicant respectfully requests reconsideration and withdrawal of the claim objection on this ground.
Applicant arguments have been fully considered but not found persuasive. Although Applicant asserts that amended claim 40 depends from claim 29 and further limits the subject matter thereof, claim 40 fails to include all imitations of claim 29, particularly the requirement that substitutions occur outside positions X0a, Xob, X1 and X2. As such, claim 40 encompasses embodiments that are excluded by claim 29 and therefore broadens, rather than narrows, the scope of the base claim.
New Rejections
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 36, 38 and 40 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.
In particular, each of claims 36 or 38 recites “a variant of any of the above peptides” and subsequently refers to “Said functional variant,” but the term “functional variant” lacks antecedent basis and is not clearly defined relative to “variant”. It is unclear whether “Variant” and “functional variant” are coextensive or represent different subsets of peptides. This ambiguity is compound by independent claim 29, from which these claims depend from, which similarly introduces a “functional variant” without clearly distinguishing it from “variant”. As a result, one of ordinary skill in the art would not be reasonably apprised of the scope of the claims, rendering them indefinite.
Furthermore, claim 40 (which is dependent on claim 29) claims “a functional variant thereof” and then “variant” in the claim and does not clearly defined the scope of either term. Although claim 29 provides certain structural limitations (1 or 2 substitutions at specific positions), it is unclear whether all peptides meeting these limitations are encompassed by the claims. Furthermore, it is unclear whether “Variant” and “functional variant” are coextensive or represent different subsets of peptides. Applicant should clarify these points of confusion.
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.
Claim(s)s 29, 34, 36, 38 and 40 are rejected under 35 U.S.C. 103 as being unpatentable over Peri (US20050059605 A1, cited in Applicant’s IDS) in view of Levy (US20110136737).
Peri discloses a peptide consisting of GIP-3-30NH2 (see paragraph 0074, “p”). Peri teaches that the peptide consisting of GIP3-30, and other peptides encompassed by “P”, are attached to an acyl group following synthesis (see paragraph 05062, paragraph 0093). Thus, the peptide GIP3-30NH2 meets the limitations of a peptide consisting of SEQ ID NO:74. However, the peptide GIP3-30NH2 is the human sequence and thus, Peri is silent to wherein the GIP3-30NH2 does not have 100% sequence identity to hGIP3-30. Peri does teach using the analogue peptides for treating diseases associated with glucose metabolism (see claims 21 and 23, diabetes in particular).
However, Levy teaches of GIP analogues useful for treatment and prevention of metabolic diseases (see abstract). Levy modification can be made to the GIP analgoue1-30 of lysine substitution at position 30 with alanine, arginine or histidine (see paragraph 0088, 0091). Levy teaches “Further exemplary substitutions are those derived from GIP of other (non-human) species, for example the methionine 14 replaced by leucine, the D at position 9 or 21 replaced by E, the histidine 18 replaced by alanine, arginine or lysine, the lysine at position 30 replaced by alanine, arginine or histidine, the alanine at position 13 replaced by leucine, and the alanine at position 28 replaced by serine” (paragraph 0088). Levy teaches that such substitutions are derived from known GIP variants including those from non-human species, and are useful for treatment of metabolic diseases.
It would have been obvious before the effective filing date of the claimed invention to modify the peptide disclosed in Peri by incorporating one or more of the amino acid substitutions taught by Levy in order to obtain a peptide with for the same therapeutic purpose, treating metabolic disorders such as diabetes. The claimed modification represents application of a known technique (amino acid substitution) to a known peptide (Peri’s human 3-30 GIP analogue) to yield predictable results, namely GIP analogues useful for therapeutic purposes such as treating diabetes (see KSR, MPEP 2143). Further, it would have been obvious to try such substitutions, as Levy provides a finite number of identified, predictable substitutions at specific positions, including a conservative substitution of Histidine for Lysine at position 30 or a Glu in place of the Asp at position 9. A person of ordinary skill in the art would have had a reasonable expectation of success in generating functional variants of the Peri peptide through such substitutions (see MPEP2143).
Additionally, the substitution of one amino acid for another, particularly among known alternatives (e.g. lysine, arginine, histidine or Asp and Glu) constitutes simple substitution of one known element for another to obtain predictable results, which is a recognized rationale supporting a conclusion of obviousness under KSR (See MPEP 2143).
Regarding claims 29 and 38, Peri in view of Levy discloses the human GIP3-30 sequence which corresponds to SEQ ID NO:74. Peri in view of Levy teach His in place of Lys at position 30 which meets the limitations of SEQ ID NO:74 with a Histidine at X2 and not having 100% sequence identity to native human GIP3-30.
Regarding claim 34, Peri in view of Levy discloses the human GIP3-30 sequence which corresponds to SEQ ID NO:74. Peri in view of Levy teach Glu in place of Asp at position 9 which meets the limitations of afunctional variant of SEQ ID NO:74 with a substitution outside the X variables and not having 100% sequence identity to native human GIP3-30.
Regarding claims 36 and 38, Peri in view of Levy discloses the human GIP3-30 sequence which corresponds to SEQ ID NO:74 and SEQ ID NO:11. Peri in view of Levy teach His in place of Lys at position 30 which meets the limitations of SEQ ID NO:11 with a Histidine at X2 and not having 100% sequence identity to native human GIP3-30.
Regarding claim 40, Peri in view of Levy discloses the human GIP3-30 sequence which corresponds to SEQ ID NO:74 and SEQ ID NO:11. Peri in view of Levy teach His in place of Lys at position 30 which meets the limitations of SEQ ID NO:91 with a Histidine at X2 and not having 100% sequence identity to native human GIP3-30.
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 USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The 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/process/file/efs/guidance/eTD-info-I.jsp.
Claims 29, 34, 36, 38, 40 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-87 of Co-pending AN19/168687. Although the claims at issue are not identical, they are not patentably distinct from each other because:
The instant application claims: A peptide selected from the group consisting of: a peptide consisting of 28 contiguous amino acids of sequence (SEQ ID NO: 74),a peptide consisting of 27 contiguous amino acids of sequence (SEQ ID NO: 75),
a peptide consisting of 26 contiguous amino acids of sequence (SEQ ID NO: 76),
wherein X0a is D or E, X0b is K, A, H, R, X1 is H, A, K, F, Y and X2 is K, H or A, and a variant of any of the above peptides having one or two substitutions outside of X0a, X0b, X1 and X2…, wherein said peptide or variant thereof is an antagonist of a GIP receptor (GIPR), with the proviso that said peptide or variant thereof does not have 100% sequence identity to native hGIP3-30 (SEQ ID NO: 1), to native hGIP4-30 (SEQ ID NO: 77) or to native hGIP5-30 (SEQ ID NO: 78)” (instant claim 29). The instant application further claims n/c- terminal acetylation or amidation (claim 29); SEQ ID NO:74 or 11 or variants thereof (see claim 38). The instant application claims variants of SEQ ID NO:11 (claims 37-38) with one to two substitutions and variants of SEQ ID NO:79 (which is human GIP3-30 with substitution at H18A).
Co-pending application 19/168687 claims human GIP(3-30), (4-30) and (5-30) with 1-6 substitutions. These sequences are instant SEQ ID NO:74-76 but do not meet the limitations of not being the sequence from human. However, Co-pending application 19/168687 encompasses functional variants with 1-6 amino acid substitutions.
Levy teaches of GIP analogues useful for treatment and prevention of metabolic diseases (see abstract). Levy modification can be made to the GIP analgoue1-30 of lysine substitution at position 30 with alanine, arginine or histidine (see paragraph 0088, 0091). Levy teaches “Further exemplary substitutions are those derived from GIP of other (non-human) species, for example the methionine 14 replaced by leucine, the D at position 9 or 21 replaced by E, the histidine 18 replaced by alanine, arginine or lysine, the lysine at position 30 replaced by alanine, arginine or histidine, the alanine at position 13 replaced by leucine, and the alanine at position 28 replaced by serine” (paragraph 0088). Levy teaches that such substitutions are derived from known GIP variants including those from non-human species, and are useful for treatment of metabolic diseases.
It would have been obvious before the effective filing date of the claimed invention to modify the peptides of Co-pending application 19/168687 by incorporating one or more of the amino acid substitutions taught by Levy in order to obtain a peptide with for the same therapeutic purpose, treating metabolic disorders such as diabetes. The claimed modification represents application of a known technique (amino acid substitution) to an peptide to yield predictable results, namely GIP analogues useful for therapeutic purposes such as treating diabetes (see KSR, MPEP 2143). Further, it would have been obvious to try such substitutions, as Levy provides a finite number of identified, predictable substitutions at specific positions, including a conservative substitution of Histidine for Lysine at position 30 or a Glu in place of the Asp at position 9. A person of ordinary skill in the art would have had a reasonable expectation of success in generating functional variants of the Co-pending application 19/168687 peptides through such substitutions (see MPEP2143).
Additionally, the substitution of one amino acid for another, particularly among known alternatives (e.g. lysine, arginine, histidine or Asp and Glu) constitutes simple substitution of one known element for another to obtain predictable results, which is a recognized rationale supporting a conclusion of obviousness under KSR (See MPEP 2143).
Furthermore, Co-pending application 19/168687 encompasses variants thereof with 1-6 substitutions.
Conclusion
No claims are allowed.
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/ERINNE R DABKOWSKI/Examiner, Art Unit 1654