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 .
Response to Election/Restriction filed on January 28, 2026 is acknowledged.
Claims 175-177 have been cancelled.
Claims 151-154, 156, 158-160, 162, 164-165, 167, 170 and 173-174 are pending in this application.
Non-Compliant Amendment
Claim 153 amendment filed on July 22, 2025 is non-compliant. In the claim amendment filed on July 22, 2025, claim 153 had been amended as follows:
PNG
media_image1.png
326
614
media_image1.png
Greyscale
PNG
media_image2.png
116
574
media_image2.png
Greyscale
. The period after “Y is H or -COOH” was not underlined. Therefore, claim 153 did not end with a period. However, in the claim amendment filed on January 28, 2026, claim 153 recites the following:
PNG
media_image3.png
416
832
media_image3.png
Greyscale
.
Claim 164 has a marking at line 5 of the claim. This is non-compliant since claim status identifier indicates “(Previously Presented)”.
For the purpose of compact prosecution, claim 153 has been interpreted as not ending with a period. For the purpose of compact prosecution, claim 164 has been interpreted as not having the underline between the terms “a second” and “cysteine”. Applicant is required to correct these errors in response to this office action.
Restriction
6. Applicant’s election without traverse of Group 1 (claims 151-154, 156, 158-160, 162, 164-165, 167, 170 and 173-174) and elect the species without traverse of 100% SEQ ID NO: 1, and the staple has the structure
PNG
media_image4.png
112
554
media_image4.png
Greyscale
in the reply filed on January 28, 2026 is acknowledged. The elected species has been searched and this appears to be free of prior art. A search was extended. Claims 151-154, 156, 158-160, 162, 164-165, 167, 170 and 173-174 are examined on the merits in this office action.
Objections
Please note, the specification has not been checked to the extent necessary to determine the presence of all possible error. Applicant's cooperation is required in correcting any errors of which applicant may become aware in the specification. MPEP § 608.01.
7. Claim 153 is objected to for the following: Claim 153 does not end with a period. Applicant is required to correct this error.
Rejections
U.S.C. 112
8. 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.
9. Claims 167 and 174 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.
10. Claim 167 recites, “A method for treating a disease or a condition in a subject in need thereof, the method comprising administering to the subject a composition comprising a therapeutically effective amount of the peptide conjugate of claim 151.” The metes and bounds of the claim is unclear. It is unclear what “diseases or conditions” are encompassed within “disease or condition in a subject in need thereof”.
11. Claim 174 recites, “The peptide conjugate of claim 173, wherein the C-terminus of the peptide is modified to produce an amide group.” Claim 174 recites a method. Claim 173 is drawn to a peptide conjugate. Claim 173 is dependent from claim 164, which is drawn to a peptide conjugate. Claim 174 reciting a method of modifying the peptide lacks antecedence.
U.S.C. 112(d)
12. 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.
13. Claim 174 is 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. 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.
14. Claim 174 recites, “The peptide conjugate of claim 173, wherein the C-terminus of the peptide is modified to product an amide group.” Claim 174 depends from claim 173, which depends from claim 164. Claim 174 does not further limit instant claims 173 and 164, since claim 174 recites a method claim.
U.S.C. 112(a)
15. 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.
16. Claims 151-154, 156, 162, 167 and 170 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
The courts have stated:
“To fulfill the written description requirement, a patent specification must describe an invention and do so in sufficient detail that one skilled in the art can clearly conclude that "the inventor invented the claimed invention." Lockwood v. American Airlines, Inc., 107 F.3d 1565, 1572, 41 USPQ2d 1961, 1966 (1997); In re Gosteli, 872 F.2d 1008, 1012, 10 USPQ2d 1614, 1618 (Fed. Cir. 1989) (" [T]he description must clearly allow persons of ordinary skill in the art to recognize that [the inventor] invented what is claimed."). Thus, an applicant complies with the written description requirement "by describing the invention, with all its claimed limitations, not that which makes it obvious," and by using "such descriptive means as words, structures, figures, diagrams, formulas, etc., that set forth the claimed invention." Lockwood, 107 F.3d at 1572, 41 USPQ2d at 1966.” Regents of the University of California v. Eli Lilly & Co., 43 USPQ2d 1398.
The MPEP lists factors that can be used to determine if sufficient evidence of possession has been furnished in the disclosure of the Application. These include “level of skill and knowledge in the art, partial structure, physical and/or chemical properties, functional characteristics alone or coupled with a known or disclosed correlation between structure and function, and the method of making the claimed invention. Disclosure of any combination of such identifying characteristics that distinguish the claimed invention from other materials and would lead one of skill in the art to the conclusion that the applicant was in possession of the claimed species is sufficient.” MPEP 2163.
Further, for a broad generic claim, the specification must provide adequate written description to identify the genus of the claim. In Regents of the University of California v. Eli Lilly & Co., the court stated:
“A written description of an invention involving a chemical genus, like a description of a chemical species, 'requires a precise definition, such as by structure, formula, [or] chemical name,' of the claimed subject matter sufficient to distinguish it from other materials. Fiers, 984 F.2d at 1171, 25 USPQ2d at 1606; In re Smythe, 480 F.2d 1376, 1383, 178 USPQ 279, 284-85 (CCPA 1973) ("In other cases, particularly but not necessarily, chemical cases, where there is unpredictability in performance of certain species or subcombinations other than those specifically enumerated, one skilled in the art may be found not to have been placed in possession of a genus. . . ."). Regents of the University of California v. Eli Lilly & Co., 43 USPQ2d 1398.
The MPEP further states that if a biomolecule is described only by a functional characteristic, without any disclosed correlation between function and structure of the sequence, it is “not sufficient characteristic for written description purposes, even when accompanied by a method of obtaining the claimed sequence.” MPEP 2163. The MPEP does state that for generic claim the genus can be adequately described if the disclosure presents a sufficient number of representative species that encompass the genus. MPEP 2163. If the genus has a substantial variance, the disclosure must describe a sufficient variety of species to reflect the variation within that genus. See MPEP 2163. Although the MPEP does not define what constitute a sufficient number of representative, the Courts have indicated what do not constitute a representative number species to adequately describe a broad generic. In Gostelli, the Court determined that the disclosure of two chemical compounds within a subgenus did not describe that subgenus. In re Gostelli, 872 F.2d at 1012, 10 USPQ2d at 1618.
In the instant case, the claims are drawn to a peptide conjugate comprising a) a peptide comprising an amino acid sequence selected from SEQ ID NO: 1-9 or 210-29, or an amino acid sequence having one amino acid addition, deletion, or substitution relative to a sequence selected from SEQ ID NO: 1-9 or 21-29, and b) a staple attached to the peptide at a first cysteine of the peptide and a second cysteine of the peptide, wherein the staple is of Formula (I):
PNG
media_image5.png
108
102
media_image5.png
Greyscale
. The generic an amino acid sequence having one amino acid addition, deletion, or substitution relative to a sequence selected from SEQ ID NO: 1-9 or 21-29, and a staple attached to the peptide at a first cysteine of the peptide and a second cysteine of the peptide, wherein the staple is of Formula (I):
PNG
media_image5.png
108
102
media_image5.png
Greyscale
do not provide ample written description for the compounds since the claims do not describe what are encompassed within the peptides and the staple of Formula (I). The peptides and staple is extremely broad and encompasses a vast number of undefined compounds. The smallest potential structure that could be encompassed by Formula (I) is two bonds from the cysteine residues to NH2. The dependent claims do not define what the peptide’s activity. Claim 167 is drawn to a method of treating diseases and conditions in a subject in nee thereof. The diseases and conditions are not defined in claim 167. The specification does not clearly define or provide examples of what qualify as compounds of the claimed invention.
As stated earlier, the MPEP states that written description for a genus can be achieved by a representative number of species within a broad generic. It is unquestionable claim 151 is broad generics with respect all possible compounds encompassed by the claims. The possible structural variations are limitless to any class of peptide or a peptide-like molecule that can form amide bonds. It must not be forgotten that the MPEP states that if a peptide is described only by a functional characteristic, without any disclosed correlation between function and structure of the sequence, it is “not sufficient characteristic for written description purposes, even when accompanied by a method of obtaining the claimed sequence.” MPEP 2163. Here, though the claims may recite some functional characteristics (treat disease or condition in need thereof), the claims lack written description because there is no disclosure of a correlation between function and structure of the compounds beyond compounds disclosed in the examples in the specification. Moreover, the specification lack sufficient variety of species to reflect this variance in the genus since the specification does not provide any examples of derivatives. The specification is void of organic molecules that functions as a peptide-like molecule that qualify for the functional characteristics claimed as a peptide or a peptide-like molecule or other peptidic molecules and other synthetic peptide or peptide-like molecule that can form amide bonds.
The specification is limited to SEQ ID NOs: 1-40. The working examples only describe the protein GLP-2 analogs (see Examples). The working examples do not describe what amino acids are essential for the peptide to maintain activity. Description of SEQ ID NOs: 1-40 is not sufficient to encompass numerous other proteins and proteases that belong to the same genus. For example, there are varying lengths, varying amino acid compositions, and numerous distinct qualities that make up the genus. The unpredictability of the effect of amino acid substitution on the function and/or property of the peptide/protein is further confirmed and discussed in Yampolsky et al (Genetics, 2005, 170: 1459-1472). Yampolsky et al teach even a conservative substitution can significantly affect the function of the protein/peptide, for example, p. 1465, Table 3.
For the staple of Formula (I), the specification describes different staples (see Table 2). The staple described (labeled) as “7 L1G” is the general formula that meets the Formula (I) of instant claims. Examples 10, 12 (L5A and C20L5A) have been reduced to practice (see Table 2).
As described above, the claim scope is potentially enormous; in comparison, the scope of the description which only includes up to two/three staples reduced to practice is not sufficient to exemplify the breadth of the genus given the claim encompasses a vast number of compounds within Formula (I). One of ordinary skill in the art would not consider peptides/staple conjugates reduced to practice representative of the full scope of the claimed genus.
There is not sufficient amount of examples provided to encompass the numerous characteristics of the whole genus claimed.
The description requirement of the patent statute requires a description of an invention, not an indication of a result that one might achieve if one made that invention. See In re Wilder, 736 F.2d 1516, 1521, 222 USPQ 369, 372-73 (Fed. Cir. 1984) (affirming rejection because the specification does "little more than outlin[e] goals appellants hope the claimed invention achieves and the problems the invention will hopefully ameliorate"). Accordingly, it is deemed that the specification fails to provide adequate written description for the genus of the claims and does not reasonably convey to one skilled in the relevant art that the inventor(s), at the time the application was filed, had possession of the entire scope of the claimed invention.
17. Claims 151 and 167 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 treating short bowel syndrome, inflammatory bowel syndrome, Crohn’s disease, ulcerative colitis and psoriasis with a peptide conjugate comprising a peptide comprising SEQ ID NOs: 1-9 or 21-29, does not reasonably provide enablement for treating ALL diseases and conditions with a peptide conjugate comprising an amino acid sequence having one amino acid addition, deletion, or substitution relative to a sequence selected from SEQ ID NO: 1-9 or 21-29. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention commensurate in scope with these claims.
The factors to be considered in determining whether a disclosure meets the enablement requirement of 35 U.S.C. 112, first paragraph, have been described in In re Wands, 8 USPQ2d 1400 (Fed. Cir. 1988). Among these factors are: (1) the nature or the invention; (2) the state of the prior art; (3) the relative skill of those in the art; (4) the predictability or unpredictability of the art; (5) the breadth of the claims; (6) the amount of direction or guidance presented; (7) the presence or absence of working examples; and (8) the quantity of experimentation necessary. When the above factors are weighed, it is the examiner’s position that one skilled in the art could not practice the invention without undue experimentation.
(1) The nature of the invention and (5) The breadth of the claims:
The claims are drawn to a peptide conjugate comprising a) a peptide comprising an amino acid sequence selected from SEQ ID NO: 1-9 or 210-29, or an amino acid sequence having one amino acid addition, deletion, or substitution relative to a sequence selected from SEQ ID NO: 1-9 or 21-29, and b) a staple attached to the peptide at a first cysteine of the peptide and a second cysteine of the peptide, wherein the staple is of Formula (I):
PNG
media_image5.png
108
102
media_image5.png
Greyscale
. The claims are further drawn to a method for treating a disease or condition in a subject in need thereof, the method comprising administering to the subject a composition comprising therapeutically effective amount of the peptide conjugate of above.
(2) The state of the prior art:
The Merck manual indicates that there are plethora of disorders known, for example, Inherited platelet function disorders, dissociative disorders and so forth (see Merck manual, Disorders enclosed). Additionally, the Merck manual indicates that there are numerous numbers of diseases, for example, glycogen storage diseases, E. coli infections and so forth (see Merck manual, Diseases enclosed).
The art recognizes that there are countless different conditions, disorders and diseases, but does not provide how to determine the individuals who are susceptible to any disorder, condition or disease list provided by the Merck manual.
With regards to the effect of amino acid substitution in a peptide or protein, the art is unpredictable is described above in the written description.
(3) The relative skill of those in the art:
The relative skill of those in the art is high.
(4) The predictability or unpredictability of the art:
Applicant’s activity is based on the determination of predicting those who are susceptible to disorders, conditions and diseases. Since the activity is based on determining the patient population that is susceptible to disorders, conditions and diseases, the predictability in the art is low. This is due to the fact that the art has recognized that there are plethora of different conditions, disorders and diseases, but does not provide how to determine the individuals who are susceptible to any disorder, condition or disease list provided by the Merck manual. For example, not all elderly people over 65 years of age suffer from Alzheimer’s disease. Additionally, not everyone suffers from prostate cancer or AIDS.
The claims don’t identify the type of disorder, condition or disease or the patient population, therefore, the claim implies that any disorder, condition or disease can be treated by the peptide conjugate of instant claims. However, the Applicant has not shown who will be susceptible to disorder, condition or disease and the types of disorder, condition or disease. There are too many variables between the patient populations, thus, it clearly shows the unpredictability of the art.
(6) The amount of direction or guidance presented and (7) The presence or absence of working examples:
Although the specification provides guidance on treating specific diseases and conditions, such as SBS, IBS, Crohn’s disease, ulcerative colitis and psoriasis, the specification does not provide guidance on treating ALL diseases and conditions. The working example is limited to peptide staple conjugate comprising, for example, instant SEQ ID NO: 1 and staple having the structures
PNG
media_image6.png
224
582
media_image6.png
Greyscale
(see L5A and C20L5A, Table 2).
The specification has not provided guidance in the way of a disclosure to how to determine individuals that need protection against any disorder, condition or disease, and that the instant peptide conjugates can treat ALL of the diseases and conditions in ALL patients. For example, Healio document (https://www.healio.com/news/dermatology/20250304/glp1-receptor-agoinists-associated-with-acne-vulgaris-in-women, pp. 1-5, 3/4/2025). Healio reference indicates that “GLP-1 receptor agonist users were 1.36 times more likely to develop acne 90 days after starting the medication vs. nonusers. Women were 53% more likely to develop acne vulgaris 1 year after starting date” (see p. 1, “Key takeaways”). Therefore, the reference teaches that peptide conjugate of instant claims would not treat dermal conditions, such as acne.
There is no clear guidance as to how to determine the patient population, since not all people suffer from the same disorder, condition or disease. Since art recognizes that there are countless different conditions, disorders and diseases, but does not provide how to determine the individuals who are susceptible to any disorder, condition or disease list provided by the Merck manual, more guidance is necessary.
(8) The quantity of experimentation necessary:
In order to treat a disease, a dosage, the subject and regimen must be identified. In order to ameliorate a disease symptoms or conditions, the end point of the treatment also needs to be identified. Since it is uncertain to predict the patient population who are susceptible for unknown disorder, condition or disease, and the Applicant have not provided the appropriate time frame at which the compound should be administered, one of ordinary skill in the art would be burdened with undue “painstaking experimentation study” to determine if the compound would be effective in treating an adult, child, or an infant from all disorder, condition or disease.
Closest Art
18. Yang et al (J. Med. Chem., 2018, 61: 3218-3223, filed with IDS) teach the instant peptide sequences of SEQ ID NOs: 1, 8, 9, 21, 28 and 29 (see Figure 1A). Yang et al teach the stapled peptide:
PNG
media_image7.png
272
422
media_image7.png
Greyscale
(see Abstract). Yang et al does not teach the staple of instant Formula (I).
19. Lear et al (J. Med. Chem., 2020, 63: 9660-9671, filed with IDS) teach GLP-1R agonist and GLP-1 analog stapled peptides (see abstract). Lear et al teach the staple of instant Formula (I) (see Figure 1B). Lear et al is a post filing reference.
20. Shen et al (US 20160317623, filed with IDS) teach the same peptide sequences as instant SEQ ID NOs: 1, 8, 9, 21, 28, 29 (see SEQ ID NOs: 49, 50, 51, 42, 47, 48, respectively). Shen et al do not teach the staple of instant Formula (I).
CONCLUSION
Claims 158-160 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Claims 151-154, 156, 162, 167, 170 and 174 are rejected.
Claims 164-165 and 173 are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JULIE HA whose telephone number is (571)272-5982. The examiner can normally be reached Monday-Thursday 5:00 am- 6:30 pm EST.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, 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.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/JULIE HA/Primary Examiner, Art Unit 1654
5/7/2026
Prosecution Insights