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 .
Applicants’ amendment to the claims filed on 5/11/2023 is acknowledged. This listing of claims replaces all prior listings of claims in the application.
Claims 1-18 are pending and examined on the merits.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 5/11/2023, 10/30/2024, 12/10/2025 is acknowledged. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement has been considered by the examiner.
Drawings
The Drawings filed on 5/11/2023 are acknowledged and accepted by the examiner.
Priority
Acknowledgement is made of this national stage entry of PCT/KR2021/016630 of Non-provisional Application No. 18/036,580, filed on 11/15/2021, which claims foreign priority under 35 U.S.C. 119(a)-(d) to Korean Patent Application No. KR10-2020-0152247 filing date 11/13/2020. The certified copy has been filed in the present application on 5/11/2023. It is noted, however, that applicant has not filed a certified copy of the English translation as required by 37 CFR 1.55.
Written Description
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 5-8 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.
MPEP 2163.II.A.2.(a).i) states, “Whether the specification shows that applicant was in possession of the claimed invention is not a single, simple determination, but rather is a factual determination reached by considering a number of factors. Factors to be considered in determining whether there is sufficient evidence of possession include the 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”.
For claims drawn to a genus, MPEP § 2163 states 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, reduction to drawings, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus. See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406.
Claim 5 is drawn to the method of claim 1, wherein the immunoglobulin Fc region has a substitution of proline for an amino acid at position 2; a substitution of glutamine for an amino acid at position 71; or a substitution of proline for an amino acid at position 2 and a substitution of glutamine for an amino acid at position 71 in an amino acid sequence of SEQ ID NO: 8. The structure and function of an amino acid sequence of SEQ ID NO: 8 is unclear because this phrase implies the changes are made in fragments or portions of SEQ ID NO: 8 irrespective whether the other amino acid positions are included or excluded.
Claim 6 is drawn to the method of claim 1, wherein the linker is a peptide linker consisting of 1 amino acid to 100 amino acids. The structure of a peptide link consisting of 1 amino acid to 100 amino acids encompasses an extremely large number of species.
With regard to the instant application claim 5, the specification discloses the following representative amino acid as encompassed by the claims (i.e. SEQ ID NO: 8). Other than the above disclosed species, there is no prior-art or disclosed teaching as to the large number of sequences that encompass an amino acid sequence of SEQ ID NO: 8. The breadth of the claims encompass any amino acid with at least 2 contiguous bases of SEQ ID NO: 8.
With regard to the instant application claim 6, the specification discloses the following representative peptide linker as encompassed by the claims (i.e. consisting of 1 to 100 amino acids). Other than the above disclosed species, there is no prior-art or disclosed teaching as to the large number of sequences that encompass a peptide linker consisting of 1 amino acid to 100 amino acids. The breadth of the claims encompass any amino acid from a single amino acid to 100 amino acids.
An adequate written description of a chemical invention also requires a precise definition, such as by structure, formula, chemical name, or physical properties, and not merely a wish or plan for obtaining the chemical invention claimed. See, e.g., Univ. of Rochester v. G.D. Searle & Co., 358 F.3d 916, 927, 69 USPQ2d 1886, 1894-95 (Fed. Cir. 2004). Here, the disclosure fails to teach which combination of amnio acids of SEQ ID NO: 8 encompasses an amino acid of SEQ ID NO: 8 (instant application claim 5). Furthermore, the disclosure fails to teach which combination of amnio acids of 1 to 100 encompasses the peptide linker as it is sufficiently broad (instant application claim 6).
Accordingly, one of skill in the art would not accept the disclosure of an amino acid sequence of SEQ ID NO: 8 with substitutions at position 2 or position 71 as being representative of all immunoglobulin Fc region substitutions as encompassed by the claims. Additionally, one of skill in the art would not accept the disclosure of a peptide linker consisting of 1 amino acid to 100 amino acids as being representative of all peptide linkers as encompassed by the claims. As such, the specification, taken with the pre-existing knowledge in the art of immunoglobulin Fc (claim 5) and peptide linkers (claim 6), fails to satisfy the written description requirement of 35 U.S.C. 112, first paragraph.
Scope of Enablement
Claim 5 is 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 amino acid substitutions at positions 2 and/or 71 of SEQ ID NO: 8, it does not reasonably provide enablement for amino acid substitutions at positions 2 and/or 71 for an amino acid sequence of SEQ ID NO: 8 as encompassed by the claims . 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 test of enablement is not whether any experimentation is necessary, but whether, if experimentation is necessary, it is undue.” In re Angstadt, 537 F.2d 498, 504, 190 USPQ 214, 219 (CCPA 1976). Factors to be considered in determining whether undue experimentation is required are summarized in In re Wands (858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988)) as follows: (A) The breadth of the claims; (B) The nature of the invention; (C) The state of the prior art; (D) The level of one of ordinary skill; (E) The level of predictability in the art; (F) The amount of direction provided by the inventor; (G) The existence of working examples; and (H) The quantity of experimentation needed to make or use the invention based on the content of the disclosure. See MPEP § 2164.01(a). The Factors considered to be most relevant to the instant rejection are addressed in detail below.
(A)The breadth of the claims:
Claim 5 is drawn to the method of claim 1, wherein the immunoglobulin Fc region has a substitution of proline for an amino acid at position 2; a substitution of glutamine for an amino acid at position 71; or a substitution of proline for an amino acid at position 2 and a substitution of glutamine for an amino acid at position 71 in an amino acid sequence of SEQ ID NO: 8. The structure and function of an amino acid sequence of SEQ ID NO: 8 is unclear because this phrase implies the changes are made in fragments or portions of SEQ ID NO: 8 irrespective whether the other amino acid positions are included or excluded.
B) The nature of the invention; C)The state of the prior art; (D) The level of one of ordinary skill; and (E) The level of predictability in the art: As noted above, the scope of the claimed variants of guanine oxidase are unlimited. The structure of the claimed amino acid with substitutions at position 2 and/or position 71 is a large number or sequences.
It is well-known in the prior art that the amino acid sequence of a polypeptide determines the polypeptide’s functional properties. The positions within a protein's sequence where modifications can be made with a reasonable expectation of success in obtaining a polypeptide having the desired activity/utility are limited in any protein and the result of such modifications is highly unpredictable. In addition, one skilled in the art would expect any tolerance to modification for a given protein to diminish with each further and additional modification, e.g., multiple substitutions. The reference of Singh et al. (Current Protein and Peptide Science, 2017; examiner cited) reviews various protein engineering methods and discloses that despite the availability of an ever-growing database of protein structures and highly sophisticated computational algorithms, protein engineering is still limited by the incomplete understanding of protein functions, folding, flexibility, and conformational changes [see p. 7, column 1, top]. The reference of Zhang et al. (Structure, 2018; examiner cited) discloses that a mutation of a residue that was predicted to be benign caused significant structural changes and unexpected effects on the function of a polypeptide [p. 1475, column 1].
It is well-known in the art that even a single amino acid alteration can alter the folding of a polypeptide. See, e.g., MPEP 2144.08.II.A.4.(c), which states, “[i]n the area of biotechnology, an exemplified species may differ from a claimed species by a conservative substitution (“the replacement in a protein of one amino acid by another, chemically similar, amino acid... [which] is generally expected to lead to either no change or only a small change in the properties of the protein.” Dictionary of Biochemistry and Molecular Biology 97 (John Wiley & Sons, 2d ed. 1989)). The effect of a conservative substitution on protein function depends on the nature of the substitution and its location in the chain. Although at some locations a conservative substitution may be benign, in some proteins only one amino acid is allowed at a given position. For example, the gain or loss of even one methyl group can destabilize the structure if close packing is required in the interior of domains. James Darnell et al., Molecular Cell Biology 51 (2d ed. 1990).”
(F) The amount of direction provided by the inventor and (G) The existence of working examples: The specification discloses the following working examples of an amino acid with substitutions at position 2 and/or 71 (i.e. SEQ ID NO: 8). Other than the above disclosed species, there is no prior-art or disclosed teaching as to the large number of sequences that encompasses an amino acid of SEQ ID NO: 8. Other than the above disclosed species, there is no prior-art or disclosed teaching as to the large number of sequences that encompasses an amino acid of SEQ ID NO: 8 through genetic modification technique such as deletion, mutation, etc. for the treatment or prevention of renal disease. Other than these working examples, the specification fails to disclose any other working examples of an amino acid sequence of SEQ ID NO: 8 for the treatment or prevention of renal disease.
In view of the overly broad scope of the claims, the lack of guidance and working examples provided in the specification, the high level of unpredictability, and the state of the prior art, undue experimentation would be necessary for a skilled artisan to make and use the entire scope of the claimed invention. Applicants have not provided sufficient guidance to enable one of ordinary skill in the art to make and use the claimed invention in a manner reasonably correlated with the scope of the claims. The scope of the claims must bear a reasonable correlation with the scope of enablement (In re Fisher, 166 USPQ 19 24 (CCPA 1970)). Without sufficient guidance, determination of having the desired biological characteristics is unpredictable and the experimentation left to those skilled in the art is unnecessarily, and improperly, extensive and undue. See In re Wands 858 F.2d 731, 8 USPQ2nd 1400 (Fed. Cir, 1988).
Claim Rejections - 35 USC § 112(b)
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 1-18 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.
Regarding claim 1 (claims 2-18 dependent thereof), the recitation of the phrase ‘each independently the same or a different kind of linker’ is indefinite because it is unclear what the scope of the phrase is intended to encompass structurally. It is unclear what the phrase ‘each independently the same or a different kind of linker’ is intended to encompass. It is unclear from the claims and specification what the phrase ‘each independently the same or a different kind of linker’ is referring to structurally and functionally as ‘a different kind of linker’ could encompass any sequence. Additionally, it is unclear what Applicant intends to mean by ‘each independently the same.’ Accordingly, the metes and bounds upon which patent protection is sought cannot be ascertained from this phrase. Appropriate correction is suggested.
Regarding claim 5, the recitation of the phrase ‘an amino acid’ is indefinite because it is unclear what the scope of the phrase is intended to encompass structurally. The phrase is unclear because it implies the changes are made in fragments or portions of seq id no: 8, irrespective whether the other amino acid positions are included or excluded. It would be unclear and scientifically incorrect if none of the amino acid positions are included in the phrase “an amino acid sequence of seq id no: 8”. Accordingly, the metes and bounds upon which patent protection is sought cannot be ascertained from this phrase. It is suggested that Applicant amend the claim to recite “…position 71 in the amino acid sequence of SEQ I D NO: 8.”
The phrase “reduced level” in claims 11, 13 is a relative term which renders the claim indefinite. The phrase “reduced level” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. The phrase "reduced level” is a relative term that renders the claim indefinite because it is unclear whether it is broad or limited. See MPEP § 2173.05(b) III A. To overcome the rejection, it is recommended that Applicant amend the claim to recite “compared to the untreated.”
Regarding claims 11, 13, the recitation of the phrase ‘wherein the administration of the pharmaceutical composition exhibits one or more’ is indefinite because it is unclear what the scope of the phrase is intended to encompass structurally. It is unclear what the ‘wherein the administration of the pharmaceutical composition exhibits one or more’ is intended to encompass. It is unclear from the claims and specification what the ‘wherein the administration of the pharmaceutical composition exhibits one or more’ is referring to structurally as it is not the “administration” that “exhibits." Accordingly, the metes and bounds upon which patent protection is sought cannot be ascertained from the claims. It is suggested that applicant clarify the meaning of the claims.
Regarding claims 14-15, the recitation of the phrase ‘an enzyme’ is indefinite because it is unclear what the scope of the phrase is intended to encompass structurally. It is unclear what the phrase ‘an enzyme’ is intended to encompass as if there are a large number of enzymes. However, claim 1 has only one enzyme “alpha-galactosidase” used in the method. It is unclear from the claims and specification what the phrase ‘an enzyme’ is referring to structurally and functionally as ‘an enzyme’ could encompass any sequence. Accordingly, the metes and bounds upon which patent protection is sought cannot be ascertained from this phrase.
Claim Rejections - 35 USC § 102
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 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)(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 1-15, 17-18 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Jung et al (US 2021/0009984 A1, Date Filed: Dec. 21, 2018, Examiner cited, recently (9-24-25) issued as US 12435328) {herein Jung} as evidenced by Torra et al (2008, International Society of Nephrology, Examiner cited) {herein Torra) and Antonowicz et al (1972, Pediat. Res, Examiner cited) {herein Antonowicz}. See MPEP 2131.01 regarding multiple reference 102 rejections.
Claims 1-15, 17-18 are drawn to a method for preventing or treating renal diseases caused by or accompanied by Fabry disease, comprising administering a pharmaceutical composition to a patient in need thereof, wherein the pharmaceutical composition comprises an enzyme fusion protein represented by the following Chemical Formula 1: [Chemical Formula 1], wherein X and X' are each alpha-galactosidase; L and L' are linkers, each independently the same or a different kind of linker; F is one polypeptide chain of an immunoglobulin Fc region; is a covalent bond; and :is a covalent or non-covalent bond.
With respect to claims 1-9, 12, 15, 17, 18, Jung teaches a method for treating Fabry’s disease utilizing a pharmaceutical composition (para 0010, para 0155, para 0056). Evidentiary reference of Torra is cited to demonstrate that Fabry’s disease causes kidney fibrosis (abstract) which is a type of kidney disease that is known by those of ordinary skill in the art to be accompanied by inflammation. Jung further teaches a method wherein the pharmaceutical composition comprises an enzyme fusion protein of Formula I (para 0010 and para 0155). The pharmaceutical composition of the fusion protein X and X' are each independently the same or a different kind of therapeutic enzyme; L and L' are linkers, each independently the same or a different kind of linker; F is an immunoglobulin Fc region; I is a covalent bond; and is a covalent or non-covalent bond (para 0010-0016). The enzyme may be selected from alpha-galactosidase (para 0031) for the production of an enzyme fusion protein including a therapeutic enzyme in the form of an antiparallel dimer (para 0200). Said fusion protein comprises a monomer that is 100% identical to the instant application SEQ ID NO: 13 (appendix A). The immunoglobulin Fc region may be aglycosylated (para 0050). The Fc region may comprise a hinge region of which may by one having a variation where a part of the hinge region is deleted (para 0119). Said hinge region is comprised of Glu-Ser-Lys-Tyr-Gly-Pro-Pro-Cys-Pro-Ser-Cys-Pro (para 0118). Absent evidence otherwise, it is the Examiner’s position that Glu-Ser-Lys-Tyr-Gly-Pro-Pro-Cys-Pro-Ser-Cys-Pro teaches the limitation of claim 4 of the instant application SEQ ID NO: 31 as the instant application SEQ ID NO: 31 is Pro-Pro-Cys-Pro, of which Glu-Ser-Lys-tyr-Gly-Pro-Pro-Cys-Pro-Ser-Cys-Pro comprises. As such, the instant application SEQ ID NO: 31 is the same as the hinge region taught by Jung since Jung teaches a part of the hinge region is deleted of which is the Examiner’s position would result in the following hinge region: Pro-Pro-Cys-Pro, which is 100% identical to the instant application SEQ ID NO: 31. Furthermore, the immunoglobulin Fc region having the amino sequence of SEQ ID NO: 8, the 2nd amino acid is substituted with proline; the 71st amino acid is substituted with glutamine; or the 2nd amino acid is substituted with proline and the 71st amino acid is substituted with glutamine (Jung: claim 33). SEQ ID NO: 8 taught by Jung is 100% identical to the instant Application SEQ ID NO: 8 (appendix B). Additionally, the linker may include at least one amino acid, specifically 10 to 50 amino acids (para 0108) of which encompasses the claimed range 1 to 100 amino acids in the instant application claim 6. The peptide linker consists of an amino acid sequence: [GS] linker, [GGGS]x linker, and [GGGGS]x linker, etc., in which x is a natural x number of 1 or greater (e.g., 1, 2, 3, 4, 5, or greater) (para 0108) and may consist of the amino acid sequence of SEQ ID NO: 11 (para 0108), of which is 100% identical to the instant application SEQ ID NO: 11 (appendix C). Jung further teaches that the frequency of administration of the pharmaceutical formulation containing the enzyme fusion protein can be significantly reduced (para 0159).
With respect to claim 10, Jung teaches a pharmaceutical composition for the treatment of lysosomal disorders (para 0003, 0009-0016). Evidentiary reference of Antonowicz is cited to demonstrate that cystic fibrosis is a lysosomal disorder (abstract). As such, it is the Examiner position that the teaching of the treatment of lysosomal disorders by Jung includes cystic fibrosis.
With respect to claim 11, Jung teaches alpha-Galactosidase A is an enzyme that hydrolyzes
globotriaosylceramide (Gb3) into lactosylceramide, and it is known that a disorder in alpha-galactosidase A leads to abnormal accumulation of Gb3 in the walls of blood vessels and various parts of the body, thereby causing Fabry's disease to occur (para 0005). Since the art teaches the structure of a pharmaceutical composition for treating renal diseases caused by or accompanied by Fabry disease, it is the Examiner’s position said pharmaceutical composition’s administration would necessarily inherently lead to one or more of the following characteristics in the individual: (i) a reduced level of lyso-Gb3 or Gb3 in kidney tissue; (ii) a reduced level of TIMP-1 (tissue inhibitor of metalloproteinase-1) in kidney tissue; (iii) a reduced level of collagen typel alpha-1 in kidney tissue; (iv) a reduced level of a-SMA (alpha-smooth muscle actin) in kidney tissue; and (v) a reduced level of soluble collagen and insoluble collagen in kidney tissue as Jung teaches the same pharmaceutical composition as the instant application (para 0010-0016).
With respect to claim 13, since the art teaches the structure of a pharmaceutical composition for treating renal diseases caused by or accompanied by Fabry disease, it is the Examiner’s position that the administration of said pharmaceutical composition would necessarily and inherently lead to one or more of the following characteristics in an individual to which the pharmaceutical composition is administered: (i) a reduced level of TNF-a in the kidney tissue; (ii) a reduced level of IL-6 in the kidney tissue; (iii) a reduced level of RANTES in the kidney tissue; and (iv) a reduced level of TNFR1 in the blood as Jung teaches the same pharmaceutical composition as the instant application (para 0010-0016).
With respect to claim 14, since the art teaches the structure of a pharmaceutical composition for treating renal diseases caused by or accompanied by Fabry disease, it is the Examiner’s position that the tissue targetability of the enzyme fusion protein for the kidney would necessarily be greater than that of an enzyme alone as Jung teaches the same fusion protein as the instant application (para 0010).
Claim Rejections - 35 USC § 103
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 16 is rejected under 35 U.S.C. 103 as being unpatentable over Jung et al (US 2021/0009984 A1, Date Filed: Dec. 21, 2018, Examiner cited, recently (9-24-25) issued as US 12435328) {herein Jung} as evidenced by Torra et al (2008, International Society of Nephrology, Examiner cited) {herein Torra) and Antonowicz et al (1972, Pediat. Res, Examiner cited) {herein Antonowicz}. Claim 16 is drawn to the method of claim 1, wherein the pharmaceutical composition is administered to an individual once every two weeks or once a month.
The teachings of Jung as applied to claims 1-15, 17-18 are set forth in the 102a2 rejection above.
With respect to claim 16, Jung teaches the pharmaceutical composition is administered to patients (para 0008). Jung further teaches that the frequency of administration of the pharmaceutical formulation containing the enzyme fusion protein can be significantly reduced (para 0159). Although the reference of Jung does not explicitly teach the limitations of claim 16, MPEP 2144.05 states"[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or frequency at which to administer the [pharmaceutical composition to an individual by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) (MPEP 2144.05 IIA)." One of ordinary skill would desire to optimize the frequency upon which the pharmaceutical composition is given to subjects depending on the particular application. It would be routine for one to arrive at the frequency for the application they intend on using the pharmaceutical composition. Therefore, the above invention would have been prima facie obvious.
However, Jung does not teach the method of claim 16, wherein the pharmaceutical composition is administered to an individual once every two weeks or once a month (claim 16).
Before the effective filing date of the claimed invention, it would have been obvious to one of ordinary skill in the art to modify the frequency upon which the pharmaceutical composition is administered to a patient to once every two weeks or once a month. Especially when Junga teaches said composition is able to maximize pharmacological efficacy by increasing the blood stability of the therapeutic enzymes and maintaining their blood concentration at a high level for a longer period of time (para 0008). Jung further teaches that the frequency of administration of the pharmaceutical formulation containing the enzyme fusion protein can be significantly reduced (para 0159).
One of ordinary skill in the art would have had a reasonable expectation of success, a reasonable level of predictability, and would be motivated to modify the frequency upon which the pharmaceutical composition is administered as Jung teaches frequent injections to maintain the blood concentration of active polypeptides may cause significant pain to the patient (para 0008). As such, reducing the frequency upon which the pharmaceutical composition is administered to the recited once every two weeks or once a month would reduce the pain of the patient while maintaining the therapeutic efficacy of the pharmaceutical composition. Therefore one of ordinary skill in the art would expect similar results if the pharmaceutical composition is injected once every two weeks or once a month. Therefore, the above invention would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention.
Double Patenting
A rejection based on double patenting of the “same invention” type finds its support in the language of 35 U.S.C. 101 which states that “whoever invents or discovers any new and useful process... may obtain a patent therefor...” (Emphasis added). Thus, the term “same invention,” in this context, means an invention drawn to identical subject matter. See Miller v. Eagle Mfg. Co., 151 U.S. 186 (1894); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Ockert, 245 F.2d 467, 114 USPQ 330 (CCPA 1957).
A statutory type (35 U.S.C. 101) double patenting rejection can be overcome by canceling or amending the claims that are directed to the same invention so they are no longer coextensive in scope. The filing of a terminal disclaimer cannot overcome a double patenting rejection based upon 35 U.S.C. 101.
Claims 1-18 are provisionally rejected under 35 U.S.C. 101 as claiming the same invention as that of claims 1-15 of prior U.S. Patent Application No. 18/036,538 {herein 538}. Said applications have a common assignee of Hanmi Pharm. This is a statutory double patenting rejection.
Independent claim 1 of ‘538 is not patentably distinct from claims 1, 10-14 of the instant application because claim 1 of ‘538 recites a method for preventing or treating neuropathy caused
by or accompanied by Fabry disease, comprising administering a pharmaceutical composition to a patient in need thereof, wherein the pharmaceutical composition comprises an enzyme fusion protein represented by the following Chemical Formula 1: wherein X and X' are each alpha-galactosidase;
L and L' are linkers, each independently the same or a different kind of linker; F is one polypeptide chain of an immunoglobulin Fc region; I is a covalent bond; and: is a covalent or non-covalent bond.
Dependent claim 2 of ‘538 is not patentably distinct from claim 2 of the instant application because claim 2 of ‘538 recites the method of claim 1, wherein the enzyme is an anti-parallel dimer formed by X and X'.
Dependent claim 3 of ‘538 is not patentably distinct from claim 3 of the instant application because claim 3 of ‘538 recites the method of claim 1, wherein the immunoglobulin Fc region is aglycosylated.
Dependent claim 4 of ‘538 is not patentably distinct from claim 4 of the instant application because claim 4 of ‘538 recites the method of claim 1, wherein the immunoglobulin Fc region includes a hinge region having an amino acid sequence of SEQ ID NO: 15.
Dependent claim 5 of ‘538 is not patentably distinct from claim 5 of the instant application because claim 5 of ‘538 recites the method of claim 1, wherein the immunoglobulin Fc region has a substitution of praline for an amino acid at position 2; a substitution of glutamine for an amino acid at
position 71; or a substitution of praline for an amino acid at position 2 and a substitution of glutamine for an amino acid at position 71 in an amino acid sequence of SEQ ID NO: 8.
Dependent claim 6 of ‘538 is not patentably distinct from claim 6 of the instant application because claim 6 of ‘538 recites the method of claim 1, wherein the linker is a peptide linker consisting of 1 amino acid to 100 amino acids.
Dependent claim 7 of ‘538 is not patentably distinct from claim 7 of the instant application because claim 7 of ‘538 recites the method of claim 6, wherein the peptide linker consists of an amino acid sequence of [GS]x, [GGGS]x, or [GGGGS]x, wherein x is a natural number of 1 to 20.
Dependent claim 8 of ‘538 is not patentably distinct from claim 8 of the instant application because claim 8 of ‘538 recites the method of claim 7, wherein the peptide linker has an amino acid sequence of SEQ ID NO: 11.
Dependent claim 9 of ‘538 is not patentably distinct from claim 9 of the instant application because claim 9 of ‘538 recites the method of claim 1, wherein the neuropathy is polyneuropathy or small fiber neuropathy.
Dependent claim 12 of ‘538 is not patentably distinct from claim 15 of the instant application because claim 12 of ‘538 recites the method of claim 1, wherein an administration frequency of the enzyme fusion protein is lesser than that of an enzyme alone.
Dependent claim 13 of ‘538 is not patentably distinct from claim 16 of the instant application because claim 13 of ‘538 recites the method of claim 1, wherein the pharmaceutical composition is administered once every two weeks or once a month.
Dependent claim 14 of ‘538 is not patentably distinct from claim 17 of the instant application because claim 14 of ‘538 recites the method of claim 1, wherein the enzyme fusion protein comprises a monomer including an amino acid sequence of SEQ ID NO: 13.
Dependent claim 15 of ‘538 is not patentably distinct from claim 18 of the instant application because claim 15 of ‘538 recites the method of claim 1, wherein X and X' are enzymes, each including an amino acid sequence the same as or different from each other.
Conclusion
Status of the claims
Claims 1-18 are pending.
Claims 1-18 are rejected.
No claims are in condition for allowance.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ERICA NICOLE JONES-FOSTER whose telephone number is (571)270-0360. The examiner can normally be reached mf 7:30a - 4:30p.
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/ERICA NICOLE JONES-FOSTER/Examiner, Art Unit 1656
/MANJUNATH N RAO/Supervisory Patent Examiner, Art Unit 1656
Appendix A
Jung SEQ ID NO: 13 vs Instant Application SEQ ID NO: 13
Query Match 100.0%; Score 3707; Length 680;
Best Local Similarity 100.0%;
Matches 680; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 MQLRNPELHLGCALALRFLALVSWDIPGARALDNGLARTPTMGWLHWERFMCNLDCQEEP 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 MQLRNPELHLGCALALRFLALVSWDIPGARALDNGLARTPTMGWLHWERFMCNLDCQEEP 60
Qy 61 DSCISEKLFMEMAELMVSEGWKDAGYEYLCIDDCWMAPQRDSEGRLQADPQRFPHGIRQL 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 DSCISEKLFMEMAELMVSEGWKDAGYEYLCIDDCWMAPQRDSEGRLQADPQRFPHGIRQL 120
Qy 121 ANYVHSKGLKLGIYADVGNKTCAGFPGSFGYYDIDAQTFADWGVDLLKFDGCYCDSLENL 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 ANYVHSKGLKLGIYADVGNKTCAGFPGSFGYYDIDAQTFADWGVDLLKFDGCYCDSLENL 180
Qy 181 ADGYKHMSLALNRTGRSIVYSCEWPLYMWPFQKPNYTEIRQYCNHWRNFADIDDSWKSIK 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 ADGYKHMSLALNRTGRSIVYSCEWPLYMWPFQKPNYTEIRQYCNHWRNFADIDDSWKSIK 240
Qy 241 SILDWTSFNQERIVDVAGPGGWNDPDMLVIGNFGLSWNQQVTQMALWAIMAAPLFMSNDL 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 SILDWTSFNQERIVDVAGPGGWNDPDMLVIGNFGLSWNQQVTQMALWAIMAAPLFMSNDL 300
Qy 301 RHISPQAKALLQDKDVIAINQDPLGKQGYQLRQGDNFEVWERPLSGLAWAVAMINRQEIG 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 RHISPQAKALLQDKDVIAINQDPLGKQGYQLRQGDNFEVWERPLSGLAWAVAMINRQEIG 360
Qy 361 GPRSYTIAVASLGKGVACNPACFITQLLPVKRKLGFYEWTSRLRSHINPTGTVLLQLENT 420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 361 GPRSYTIAVASLGKGVACNPACFITQLLPVKRKLGFYEWTSRLRSHINPTGTVLLQLENT 420
Qy 421 MQMSLKDLLGGGGSGGGGSGGGGSGGGGSGGGGSGGGGSPPCPAPEFLGGPSVFLFPPKP 480
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 421 MQMSLKDLLGGGGSGGGGSGGGGSGGGGSGGGGSGGGGSPPCPAPEFLGGPSVFLFPPKP 480
Qy 481 KDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFQSTYRVVSVLT 540
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 481 KDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFQSTYRVVSVLT 540
Qy 541 VLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTC 600
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 541 VLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTC 600
Qy 601 LVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSV 660
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 601 LVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSV 660
Qy 661 MHEALHNHYTQKSLSLSLGK 680
||||||||||||||||||||
Db 661 MHEALHNHYTQKSLSLSLGK 680
Appendix B
Jung SEQ ID NO: 8 vs Instant Application SEQ ID NO: 8
Query Match 100.0%; Score 1186; Length 222;
Best Local Similarity 100.0%;
Matches 221; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 PSCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHN 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 2 PSCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHN 61
Qy 61 AKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREP 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 62 AKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREP 121
Qy 121 QVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFL 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 122 QVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFL 181
Qy 181 YSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK 221
|||||||||||||||||||||||||||||||||||||||||
Db 182 YSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK 222
Appendix C
Jung SEQ NO: 11 vs Instant Application SEQ ID NO: 11
Query Match 100.0%; Score 168; Length 30;
Best Local Similarity 100.0%;
Matches 30; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 GGGGSGGGGSGGGGSGGGGSGGGGSGGGGS 30
||||||||||||||||||||||||||||||
Db 1 GGGGSGGGGSGGGGSGGGGSGGGGSGGGGS 30