DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Priority
The instant application, filed 02/28/2023, is a 371 filing of PCT/US21/48695, filed 09/01/2021, which claims foreign priority to 63/073,256, filed 09/01/2020.
Information Disclosure Statement
The Information Disclosure Statement filed on 02/28/2023 is acknowledged and found to be in compliance with the provisions of 37 CFR § 1.97. Accordingly, the information disclosure statement is considered.
Restriction/Election
Applicant’s election without traverse of Group I in the reply filed on 10/29/2025 is acknowledged.
In accordance with the MPEP § 803.02, if upon examination of the elected species, no prior art is found that would anticipate or render obvious the instant invention based on the elected species, the search of the Markush-type claim will be extended. If prior art is then found that anticipates or renders obvious the non-elected species, the Markush-type claim will be rejected. It should be noted that the prior art search will not be extended unnecessarily to cover all non-elected species. Should Applicant overcome the rejection by amending the claim, the amended claim will be reexamined. The prior art search will be extended to the extent necessary to determine patentability of the Markush-type claim. In the event prior art is found during reexamination that renders obvious or anticipates the amended Markush-type claim, the claim will be rejected and the action made final.
As per MPEP § 803.02, the Examiner will determine whether the entire scope of the claims is patentable. Applicants' elected species (Figure 1) does not make a contribution over the prior art of record.
Figure 1. Elected Species
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Figure 1. Compound EO-18
Status of Claims
Claims 1-32 are pending in the instant application. Claims 4-32 are withdrawn from further consideration pursuant to 37 CFR § 1.142(b), as being drawn to a non-elected invention and species. Therefore, claims 1-3 read on an elected invention and species and are therefore under consideration in the instant application and are examined on the merits as such.
Specification
The disclosure is objected to because of the following informalities:
the specification includes warped images of the two-dimensional structures of the compounds of the instant claims. The aspect ratio is not consistent among the structures, and the compounds look as if they have an improperly resized. For instance, see compounds EO-1 through EO-23 (pages 22-27), in contrast to the properly sized and proportioned EO-24 and EO-25 (page 28). Examples of some compounds are herein included:
Warped image:
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Properly sized image:
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The vast majority of the compounds listed within the instant specification are warped in this way.
Further regarding claim 2, Compounds EO-1, 2, 3, 4, 6, 11, 12, and 23 improperly designate the number of hydrogen in the substituent on R3. For instance, amino substituent is written as NH2 instead of NH2. That is, the number should be listed as a subscript instead of a regular number, in line with the text.
Further regarding claim 2, Compound EO-12 defines the amino substituent as Nh2 instead of NH2. This objection is proper as Nh is the elemental symbol of Nihonium, with atomic number 113.
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Appropriate correction is required.
Drawings
The drawings filed on 02/28/2023 are objected to for the following reasons:
The different data types are indistinguishable in Figure 2A, 2B, 4B, and 4C. The original figures rely on color-coding of the data, a feature not available in the black and white drawings. The figures must be remade with fewer data points within the figure, or different shapes or line-types used to describe the different data points, ensuring the data is not overlapping and is distinguishable.
Any structural detail that is essential for a proper understanding of the disclosed invention should be shown in the drawing. MPEP § 608.02(d). Corrected drawing sheets in compliance with 37 CFR § 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR § 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Claim Rejections - 35 U.S.C. § 112(a)
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 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 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.
Claims 1-3 of the instant application are drawn to compounds having following substituents:
R1 is selected from OH, O—CH3, O—CH2CH3, O—CH(CH3)2, NH—CH3, and NH—CH2CH3;
R2 is selected from H, F, Cl, CH3, CF3, OCH3, CH2CH3, OCH2CH3;
R3 is selected from H, OH, CH3, CF3, NH2, F, Cl, OCH3, and NHCOCH3;
X1 selected from H, F, Cl, OH, CH3, CF3, CH2CH3, OCH3, OCH2CH3, and —CO—CH3
X2 selected from H, F, Cl, OH, CH3, CF3, CH2CH3, OCH3, OCH2CH3, and —CO—CH3
X3 is selected from H, F, Cl, OH, CH3, CF3, CH2CH3, OCH3, OCH2CH3, and —CO—CH3;
Y1 is selected from H, F, Cl, CH3, CF3, OCH3, and CH2CH3
Y2 is selected from H, F, Cl, CH3, CF3, OCH3, and CH2CH3
Y3 is selected from H, F, Cl, CH3, CF3, OCH3, and CH2CH3
Y4 is selected from H, F, Cl, CH3, CF3, OCH3, and CH2CH3;
Z is selected from H, F, Cl, CH3, CF3, OCH3, CH2CH3, CH2NH2, and CH2CH2NH2;
R4 is selected from:
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R5 is selected from H, OH, CH3, CF3, NH2, F, Cl, OCH3, and NHCOCH3
35 U.S.C. § 112(a) and the first paragraph of pre-AIA 35 U.S.C. § 112 require that the "specification shall contain a written description of the invention ...." This requirement is separate and distinct from the enablement requirement. Ariad Pharm., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1340, 94 USPQ2d 1161, 1167 (Fed. Cir. 2010) (en banc); Vas-Cath, Inc. v. Mahurkar, 935 F.2d 1555, 1560, 19 USPQ2d 1111,1114 (Fed. Cir. 1991); see also Univ. of Rochester v. G.D. Searle & Co., 358 F.3d 916, 920-23, 69 USPQ2d 1886, 1890-93 (Fed. Cir. 2004) (discussing the history and purpose of the written description requirement); In re Curtis, 354 F.3d 1347, 1357, 69 USPQ2d 1274, 1282 (Fed. Cir. 2004) ("conclusive evidence of a claim’s enablement is not equally conclusive of that claim’s satisfactory written description"). The written description requirement has several policy objectives. "[T]he ‘essential goal’ of the description of the invention requirement is to clearly convey the information that an applicant has invented the subject matter which is claimed." In re Barker, 559 F.2d 588, 592 n.4, 194 USPQ 470, 473 n.4 (CCPA 1977). Another objective is to convey to the public what the applicant claims as the invention. See Regents of the Univ. of Cal. v. Eli Lilly, 119 F.3d 1559, 1566, 43 USPQ2d 1398, 1404 (Fed. Cir. 1997), cert, denied, 523 U.S. 1089 (1998). "The ‘written description’ requirement implements the principle that a patent must describe the technology that is sought to be patented; the requirement serves both to satisfy the inventor’s obligation to disclose the technologic knowledge upon which the patent is based, and to demonstrate that the patentee was in possession of the invention that is claimed." Capon v. Eshhar, 418 F.3d 1349, 1357, 76 USPQ2d 1078, 1084 (Fed. Cir. 2005). Further, the written description requirement promotes the progress of the useful arts by ensuring that patentees adequately describe their inventions in their patent specifications in exchange for the right to exclude others from practicing the invention for the duration of the patent’s term.
To satisfy the written description requirement, a patent specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention. See, e.g., Moba, B.V. v. Diamond Automation, Inc., 325 F.3d 1306, 1319, 66 USPQ2d 1429, 1438 (Fed. Cir. 2003); Vas-Cath, Inc. v. Mahurkar, 935 F.2d at 1563, 19 USPQ2d at 1116.
An applicant shows possession of the claimed invention by describing the claimed invention with all of its limitations using such descriptive means as words, structures, figures, diagrams, and formulas that fully set forth the claimed invention. Lockwood v. Amer. Airlines, Inc., 107 F.3d 1565, 1572, 41 USPQ2d 1961, 1966 (Fed. Cir. 1997). Possession may be shown in a variety of ways including description of an actual reduction to practice, or by showing that the invention was "ready for patenting" such as by the disclosure of drawings or structural chemical formulas that show that the invention was complete, or by describing distinguishing identifying characteristics sufficient to show that the applicant was in possession of the claimed invention. See, e.g., Pfaffv. Wells Bees., Inc., 525 U.S. 55, 68, 119 S.Ct. 304, 312, 48 USPQ2d 1641, 1647 (1998); EliLilly, 119 F.3d at 1568, 43 USPQ2d at 1406; Amgen, Inc. v. Chugai Pharm.,927 F.2d 1200, 1206, 18 USPQ2d 1016, 1021 (Fed. Cir. 1991). An application specification may show actual reduction to practice by describing testing of the claimed invention.
In the present case, the important factors leading to a conclusion of inadequate written description is the absence of any working example of the invention as claimed, and the lack of predictability in the art.
In the instant specification, there is no disclosure of compounds having the following claimed substituents:
R1 as O—CH(CH3)2 and NH—CH2CH3;
R2 as H, F, Cl, CF3, CH2CH3, OCH2CH3;
R3 as OH, CF3, F, Cl, OCH3, and NHCOCH3;
X1 as F, Cl, OH, CH3, CF3, CH2CH3, OCH3, OCH2CH3, and —CO—CH3
X2 as F, Cl, CH3, CF3, CH2CH3, OCH3, OCH2CH3, and —CO—CH3
X3 as, F, Cl, CH3, CF3, CH2CH3, OCH3, OCH2CH3, and —CO—CH3;
Y1 as F, Cl, CF3, OCH3, and CH2CH3
Y2 is as F, Cl, CF3, OCH3, and CH2CH3
Y3 as F, Cl, CF3, OCH3, and CH2CH3
Y4 as F, Cl, CH3, CF3, OCH3, and CH2CH3;
Z as H, F, Cl, CF3, OCH3, CH2CH3, CH2NH2, and CH2CH2NH2;
R4 as
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R5 as OH, CF3, F, Cl, OCH3, and NHCOCH3
The instant specification (pages 61-64 and 84-98) teaches compounds which are characterized as having only the following substituents:
R1 is OH, O—CH3, O—CH2CH3, and NH—CH3,
R2 is CH3 and OCH3,
R3 is H, CH3, and NH2,
X1 is H,
X2 is H and OH
X3 is H and OH
Y1 is H and CH3
Y2 is H and CH3
Y3 is H and CH3
Y4 is H
Z is CH3
R4 is
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R5 is H, CH3, and NH2,
Therefore, the compounds described in the instant specification detail only a limited number of the total substituents claimed (see substituents 1-13, above). All working examples presented in the instant specification are related to the compounds containing a fraction of the total claimed substituents (see substituents 27-39, above).
There are no working examples in the instant specification for the wide range of substituents claimed, but for which evidence of possession has not been provided (see substituents 14-26). Thus the instant specification does not provide any evidence that Applicant was in possession of the claimed invention prior to the effective filing of the instant application.
Vas-Cath Inc. Mahurkar, 19 USPQ2d 1111, makes clear the "applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the 'written description' inquiry, whatever is now claimed." (See page 1117.) The specification does not "clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed." (See Vas-Cath at page 1116).
Finally, University of California v. Eli Lilly and Co., 43 USPQ2d 1398, 1404, 1405 held that: ...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.
It is noted that the pharmaceutical art is unpredictable, requiring each embodiment to be individually assessed for physiological activity. For inventions in emerging and unpredictable technologies, or for inventions characterized by factors not reasonably predictable which are known to one of ordinary skill in the art, more evidence is required to show possession. For example, disclosure of only a method of making the invention and the function may not be sufficient to support a product claim other than a product-by-process claim. See, e.g., Fiers v. Revel, 984 F.2d at 1169, 25 USPQ2d at 1605; Amgen, 927 F.2d at 1206, 18 USPQ2d at 1021.
Thus, since Applicant has not described in adequate detail methods to synthesize compounds containing the claimed substituents, or provided evidence that said compounds have been characterized, or that they exist, an ordinary skilled artisan could not completely envisage Applicants’ invention. Moreover, it is clear that the written description requirement has not been met since Applicant has not provided any evidence that Applicant was in possession of the claimed invention prior to the effective filing of the instant application. Thus, claims 1-3 of the instant application are not supported by the instant specification and a rejection under 35 U.S.C. § 112 (a) for failing to comply with the written description requirement is proper.
Claim Rejections - 35 USC § 112(d)
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 2 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, amend the claim to place the claim in proper dependent form, rewrite the claim in independent form, or present a sufficient showing that the dependent claim complies with the statutory requirements.
Claim 2 recites the limitation NO2 in position R3, in compound EO-3. This limitation contains subject matter that is not within the scope of the claim on which it depends, because the specific substituent is not defined within the limitations of R3 as recited in claim 1.
Further regarding claim 2, the claim recites the limitation -OH in position R2, in compound EO-10. This limitation contains subject matter that is not within the scope of the claim on which it depends, because the specific substituent is not defined within the limitations of R2 as recited in claim 1.
Further regarding claim 2, the claims recite the limitation
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in position R4, in compound EO-25. This limitation contains subject matter that is not within the scope of the claim on which it depends, because the specific substituent is not defined within the limitations of R4 as recited in claim 1.
Claim Rejections – 35 U.S.C. § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. § 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1-3 are rejected under 35 U.S.C. § 102(a)(1) and (a)(2) as being anticipated by Zhi et al. (WO 2005118551 A2, published December 15, 2005), hereinafter Zhi.
The instant claims are drawn to a compound of Formula (I) and a pharmaceutical composition thereof.
Zhi teaches compounds which modulate the activity of thrombopoietin (Title). Specifically, Zhi discloses compound 128 (Example 28, page 67, claim 6), and a pharmaceutical composition thereof (see Figure 2a). Compound 128 anticipates the instant claims wherein,
Figure 2. Structural comparison of prior art compound and instantly claimed Formula (I)
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Figure 2. a) CAS Registry Number: RN 871361-53-4 b) instantly claimed Formula (I)
1Y, Y2, Y3, Y4, 1X, X2, X3, and R2 are H
R1 is OH
Z is CH3
R3 are H and CH3
Claim Rejections - 35 U.S.C. § 103
The following is a quotation of pre-AIA 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.
Claims 1-3 are rejected under 35 U.S.C. § 103 as being unpatentable over Zhi et al. (WO 2005118551 A2, published December 15, 2005), hereinafter Zhi, in view of Patani et al., (Chem Rev Volume 96, pg. 3147-3176, published December 19, 1996), hereinafter Patani.
The instant claims are drawn to a compound of Formula (I), elected to be compound EO-18, and a pharmaceutical composition thereof.
Zhi teaches compounds which modulate the activity of thrombopoietin (Title). Specifically, Zhi discloses compound 128 (Example 28, page 67, claim 6), and a pharmaceutical composition thereof (see Figure 3a). Compound 128 which renders obvious the elected species wherein,
1Y, Y2, Y3, Y4, 1X, X2, X3, and R2 are H
R1 is OH
Z is CH3
R3 are H and CH3
Figure 3. Structural comparison of prior art compound and instant elected species
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Figure 3. a) Zhi CAS Registry Number: RN 871361-53-4; b) Elected species, compound EO-18
Zhi fails to teach the elected species, exactly. Specifically, Zhi fails to teach a compound wherein which Y3 is CH3. However, Zhi teaches wherein R2 and R3 may be methyl, corresponding to position Y3 in the instant application. A person of ordinary skill in the art would be expressly motivated to substitute methyl for hydrogen in the prior art compound, following the teachings of Patani, who teaches rational approaches in drug design, to develop novel and more-potent therapeutics.
Wherein Y3 is H in the prior art compound, and Y3 is CH3 in the elected species: this substitution is considered to be a classical bioisosteric replacement, well-known to the ordinary artisan in skilled in rational drug design. With respect to classical bioisosteres, Patani teaches that the substitution of hydrogen by methyl is one of the more commonly employed isosteric replacements (page 3152, section II, segment A, item 4 of Patani). This teaching is based on Grimm’s Hydride displacement law which describes how chemical groups can mimic each other, and is one of the most crucial lead modification tools in rational drug design. Therefore, a person having ordinary skill in the art prior to the effective filing date of the instant claims would be directly motivated to modify the compounds described by Zhi to include methyl in the place of hydrogen, as taught by Patani, on the Y3 substituent, in order to chemically modify the original compound, with a reasonable expectation of success.
Correspondence
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Sophia P. Hirakis whose telephone number is +1 (571) 272-0118. The examiner can normally be reached within the hours of 5:00 am to 5:00pm EST, Monday through Friday.
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/SOPHIA P HIRAKIS/Examiner, Art Unit 1623
/ADAM C MILLIGAN/Supervisory Patent Examiner, Art Unit 1623