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 .
Response to Amendment
Applicant’s amendment filed 10 November 2025 has been received and entered. Claim 1 has been amended and claim 23 has been canceled. Claims 1-22 are currently pending and under consideration in the instant Office action.
Election/Restrictions
Applicant’s election without traverse of Group I in the reply filed on 10 November 2025 is acknowledged.
Information Disclosure Statement
The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
The information disclosure statements (IDS) submitted on 17 September 2025 and 10 November 2025 have been considered by the examiner.
Drawings
Color photographs and color drawings are not accepted in utility applications unless a petition filed under 37 CFR 1.84(a)(2) is granted. Any such petition must be accompanied by the appropriate fee set forth in 37 CFR 1.17(h), one set of color drawings or color photographs, as appropriate, if submitted via the USPTO patent electronic filing system or three sets of color drawings or color photographs, as appropriate, if not submitted via the via USPTO patent electronic filing system, and, unless already present, an amendment to include the following language as the first paragraph of the brief description of the drawings section of the specification:
Paragraphs [0025]-[0027] and [0029] in the specification refer to color (green and red) with regard to Figures 12-14 and 16. Therefore, it would seem that these figures were meant to be viewed in color. Figures 12-14 and 16 are currently in black and white. The details which the color is meant to convey are lost in the current form.
Color photographs will be accepted if the conditions for accepting color drawings and black and white photographs have been satisfied. See 37 CFR 1.84(b)(2).
The drawings are objected to because they do not comply with 37 CFR 1.84(a)(1), 1.84(l) and 1.84(b)(1).
(a) Drawings. There are two acceptable categories for presenting drawings in utility and design patent applications.
(1) Black ink. Black and white drawings are normally required. India ink, or its equivalent that secures solid black lines, must be used for drawings;
(b) Photographs.—
(1) Black and white. Photographs, including photocopies of photographs, are not ordinarily permitted in utility and design patent applications. The Office will accept photographs in utility and design patent applications, however, if photographs are the only practicable medium for illustrating the claimed invention. For example, photographs or photomicrographs of: electrophoresis gels, blots (e.g., immunological, western, Southern, and northern), autoradiographs, cell cultures (stained and unstained), histological tissue cross sections (stained and unstained), animals, plants, in vivo imaging, thin layer chromatography plates, crystalline structures, and, in a design patent application, ornamental effects, are acceptable. If the subject matter of the application admits of illustration by a drawing, the examiner may require a drawing in place of the photograph. The photographs must be of sufficient quality so that all details in the photographs are reproducible in the printed patent.
(l) Character of lines, numbers, and letters. All drawings must be made by a process which will give them satisfactory reproduction characteristics. Every line, number, and letter must be durable, clean, black (except for color drawings), sufficiently dense and dark, and uniformly thick and well-defined. The weight of all lines and letters must be heavy enough to permit adequate reproduction. This requirement applies to all lines however fine, to shading, and to lines representing cut surfaces in sectional views. Lines and strokes of different thicknesses may be used in the same drawing where different thicknesses have a different meaning.
Figure 3 is not compliant with 37 CFR 1.84(a)(1) and (l). See screenshot below:
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Figure 4 is not compliant with 37 CFR 1.84(a)(1) and (l). See screenshot below:
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Figure 5 is not compliant with 37 CFR 1.84(a)(1), (b)(1) and (l).
Figure 6 is not compliant with 37 CFR 1.84(a)(1) and (l).
Figure 7B is not compliant with 37 CFR 1.84(b)(1) as the details are not visible.
Figure 10 is not compliant with 37 CFR 1.84(b)(1) as the details are not visible.
Figure 11 is not compliant with 37 CFR 1.84(a)(1) and (l).
Figure 12 is not compliant with 37 CFR 1.84(b)(1) as the details are not visible.
Figure 13 is not compliant with 37 CFR 1.84(a)(1), (b)(1) and (l).
Figure 14 is not compliant with 37 CFR 1.84(a)(1), (b)(1) and (l).
Figure 15 is not compliant with 37 CFR 1.84(a)(1), (b)(1) and (l).
Figure 16 is not compliant with 37 CFR 1.84(a)(1), (b)(1) and (l).
Figure 17 is not compliant with 37 CFR 1.84(a)(1) and (l).
Figure 22A is not compliant with 37 CFR 1.84(b)(1) as the details are not visible.
Specification
Applicant is reminded of the proper content of an abstract of the disclosure.
A patent abstract is a concise statement of the technical disclosure of the patent and should include that which is new in the art to which the invention pertains. The abstract should not refer to purported merits or speculative applications of the invention and should not compare the invention with the prior art.
Where applicable, the abstract should include the following: (1) if a machine or apparatus, its organization and operation; (2) if an article, its method of making; (3) if a chemical compound, its identity and use; (4) if a mixture, its ingredients; (5) if a process, the steps.
The abstract should be in narrative form and generally limited to a single paragraph within the range of 50 to 150 words in length.
See MPEP § 608.01(b) for guidelines for the preparation of patent abstracts.
Applicant is reminded of the proper language and format for an abstract of the disclosure.
The abstract should be in narrative form and generally limited to a single paragraph on a separate sheet within the range of 50 to 150 words in length. The abstract should describe the disclosure sufficiently to assist readers in deciding whether there is a need for consulting the full patent text for details.
The language should be clear and concise and should not repeat information given in the title. It should avoid using phrases which can be implied, such as, “The disclosure concerns,” “The disclosure defined by this invention,” “The disclosure describes,” etc. In addition, the form and legal phraseology often used in patent claims, such as “means” and “said,” should be avoided.
The abstract of the disclosure is objected to because (1) because the recitation of “the present disclosure provides” is language to be avoided and (2) because it is not directed to that which the invention pertains. The “invention” is defined by the claims and the claims are not directed to “other compositions” which “may act on the IGF-1 pathway via another mechanism”. The only compositions which are provided for the invention to which the instant application pertains are IGF-1 molecules and this is not reflected in the current abstract. Further, there are no “related methods, kits or pharmaceutical compositions for treating eye-related disorders” as the only conditions encompassed are dry eye or Meibomian gland dysfunction. A corrected abstract of the disclosure is required and must be presented on a separate sheet, apart from any other text. See MPEP § 608.01(b).
The title of the invention is not descriptive. A new title is required that is clearly indicative of the invention to which the claims are directed. As the claims are limited to treating dry eye or Meibomian gland dysfunction by administration of an IGF-1, the title should reflect this aspect of the invention.
The use of the following terms, which are trade names or marks used in commerce, have been noted in this application
“CellTiter-Glo®” – see Figure 6 and [0114].
CLARIOstar®Plus Microplate Reader – see [0114].
LipidTOX™ – see [0022], [0028], [0125], [0130], [0153].
TRIzol® - see [0134].
GloMAX® – see [0154].
The terms should be accompanied by the generic terminology; furthermore the terms should be capitalized wherever they appear or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the terms.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks. In view of the number of trademarks which were not properly identified in the specification, Applicant should review the entire specification to make sure every instance of a trademark is properly identified and is accompanies by the generic terminology.
Claim Objections
Claim 20 is objected to because of the following informalities: the claim recites “synthetic or semi-synthetic polymer or glyceride” in lines 4-5. The claim is not clear due to the punctuation or lack thereof with regard to this recitation. Glyceride is a monomer and can be a building block of a polymer. Possibly, the second recitation of “or” may have been intended to be an “of”. Alternately, the second “or” could be replaced by a comma. Either way, the current recitation does not make sense and should be amended for clarity purposes. Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1-22 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 a method of treatment comprising an IGF-1 agonist molecule, does not reasonably provide enablement for a method of treatment by administering an IGF-1 variant as currently claimed. 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 use the invention commensurate in scope with these claims.
Claims 1-22 are directed to methods of treatment which require the administration of an “IGF-1 variant”. However, none of the claims require that the IGF-1 variant possess any particular biological activity such as being an agonist or an antagonist. The claims merely require that the IGF-1 variant have some degree of amino acid sequence identity to SEQ ID NO:1 or have a substitution at position 3 (claim 3) or have reduced affinity for an IGFBP (claim 2). The instant claims are not enabled for IGF-1 variants which are not agonists of the IGF-1 receptor. The claimed method requires activation of the IGF-1 receptor yet the claims are directed to IGF-1 variants in general and there is no requirement that they possess any particular functional activity. Therefore, the claims are not enabled for their full scope as they are currently drafted.
Claims 1-22 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claim 1 is directed to a method of treating dry eye disorder or Meibomian gland dysfunction by administration of an IGF-1 variant having at least 90% sequence identity to SEQ ID NO:1 wherein the administration results in an increase of lipid content of the Meibomian glands of the subject. Claim 2 recites that the IGF-1 variant has reduced affinity to at least one IGF binding protein relative to wild-type IGF-1 to the IGFBP. Claim 3 recites that the IGF-1 variant has an amino acid substitution at position 3 relative to wild-type IGF-1. Claims 8-17 require particular physiological outcomes from the administration of the IGF-1 variant. Claims 21-22 require that the IGF-1 variant have at least 95% or 97% amino acid sequence identity to SEQ ID NO:1.
However, none of the claims positively recite an actual structure for the IGF-1 variant of the instant claims. The instant specification discloses IGF-1 having the amino acid sequence of SEQ ID NO:1 and 4 other IGF-1 molecules:
IGF-1 Ea (SEQ ID NO:7) which is an IGF-1 precursor (with C-terminal extension compared to SEQ ID NO:1).
IGF-1 Des 1-3 R37X (SEQ ID NO:6) which is IGF-1 with a deletion of amino acids at positions 1-3 and 37 relative to SEQ ID NO:1.
IGF-1 Des 1-3 (SEQ ID NO:8) which is IGF-1 with a deletion of amino acids at positions 1-3 relative to SEQ ID NO:1.
IGF-1 E3R (SEQ ID NO:4) which is IGF-1 with a substitution of arginine at position 3 relative to SEQ ID NO:1.
Therefore, the only “variants” of IGF-1 which are disclosed are IGF-1 with the deletion of the amino acids at positions 1-3, the amino acid at position 37 or the substitution of the amino acid at position 3 with arginine. These are the only “IGF-1 variants” for which the instant specification provides an adequate written description. The specification fails to provide an adequate written description of the full scope of IGF-1 variants encompassed by the instant claims.
As pointed out above, the specification discloses only 3 variations from the native IGF-1 amino acid sequence of SEQ ID NO:1 (deletion of amino acids 1-3, substitution of position 3 and deletion of position 37. These variants have written description. However, the claims encompass variants with up to 10% variation and there is no requirement that the variant possess any particular activity as well as no guidance or direction as to which alterations could be made and still result in an IGF-1 molecule which would have the necessary functionality to be useful in the claimed method. Claim 2 requires that the IGF-1 variant have reduced affinity for IGFBP but the instant specification fails to provide an adequate written description of what alterations could be or should be made to IGF-1 to achieve this effect outside of the known modification in the prior art of deleting the first 3 amino acids or substituting position 3 of IGF-1 (see Dubaquie et al. Biochemistry 38: 6386-6396, 1999 and Ballard et al. Int. J. Biochem. Cell Biol. 28: 1085-1087, 1996).
The instant specification fails to provide an adequate written description which encompasses the breadth of the current claims in that only 3 variants of IGF-1 have been provided and the specification lacks guidance as to what positions may be modified and be tolerant to modification and still result in a protein that has the required functionality necessary to practice the method of the claims. Outside of the 3 variations which are disclosed and which were already known in the prior art before the effective filing date of the claimed invention, there is no disclosure of structure/function relationships from which a person of ordinary skill in the art would be able to make reasonable assumptions as to any other amino acid positions or substitutions which possibly might result in an IGF-1 variant with any particular functionality with as much as 10% variation as encompassed by the instant claims.
To provide evidence of possession of a claimed genus, the specification must provide sufficient distinguishing identifying characteristics of the genus. The factors to be considered include disclosure of complete or partial structure, physical and/or chemical properties, functional characteristics, structure/function correlation, methods of making the claimed product, or any combination thereof. In this case, while the specification teaches 3 IGF-1 variants, the specification does not provide sufficient description for the full breadth of the claims with regard to any other modifications or variability which would result in the functionality necessary for the claimed method. Accordingly, in the absence of sufficient recitation of distinguishing identifying characteristics, the specification does not provide adequate written description of the claimed genus.
Vas-Cath Inc. v. Mahurkar, 19 USPQ2d 1111 (Fed. Cir. 1991), clearly states that “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).
The skilled artisan cannot envision the detailed chemical structure of the encompassed variants with substitutions, deletions and/or additions with the resultant growth factor variants having the requisite activity required for the claimed method and therefore conception is not achieved until reduction to practice has occurred, regardless of the complexity or simplicity of the method of isolation. Adequate written description requires more than a mere statement that it is part of the invention and reference to a potential method of isolating it. The compound itself is required. See Fiers v. Revel, 25 USPQ2d 1601 at 1606 (CAFC 1993) and Amgen Inc. v. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016 (Fed. Cir. 1991).
One cannot describe what one has not conceived. See Fiddes v. Baird, 30 USPQ2d 1481 at 1483 (BPAI 1993). In Fiddes, claims directed to mammalian FGF’s were found to be unpatentable due to lack of written description for that broad class. In Fiddes, the specification provided only the bovine sequence.
Therefore, the claims do not meet the written description provision of 35 U.S.C. §112, first paragraph as the specification does not provide an adequate written description of the encompassed genus of IGF-1 variants of the instant claims. Applicant is reminded that Vas-Cath makes clear that the written description provision of 35 U.S.C. §112 is severable from its enablement provision (see page 1115).
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 1-22 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.
Claims 1-22 all recite “IGF-1 variant”, but none of the claims actually define the ”IGF-1 variant” in a meaningful way such that the metes and bounds of what is being claimed is clear. The recitation of “variant” only implies that the IGF-1 is different from a wild-type IGF-1, but even in that context, the “IGF-1 variant” could still be a wild-type molecule when compared to a wild-type IGF-1 which is different (such as species variants). Therefore, the claims do not appear to be defining what is being administered by what the compound is but rather by what it isn’t. This is further complicated by the fact that an IGF-1 which is 100% identical to SEQ ID NO:1 would meet the only structural limitation in claim 1, but SEQ ID NO:1 is a wild-type IGF-1. So, is an IGF-1 which is 100% identical to SEQ ID NO:1 also an IGF-1 variant? Possibly because it is a “variant” when compared to IGF-1 from a different species which is not 100% identical to SEQ ID NO:1, but is that the intent of the claim? Therefore, the metes and bounds of the claims are indefinite.
Claim 2 recites that the IGF-1 variant has reduced affinity to at least one IGF binding protein relative to “wild-type IGF-1” to the IGFBP. However, the metes and bounds of “wild-type IGF-1” are unclear and therefore the claim is indefinite. The art does not recognize a singular “wild-type IGF-1” as any IGF-1 protein from any mammalian species, including naturally occurring variants, would be considered a “wild-type IGF-1”. Without a specific wild-type IGF-1 for comparison, the claim is indefinite as different IGF-1 proteins will have different affinities for different IGFBP proteins.
Claim 20 recites “wherein the pharmaceutical composition comprises one or more pharmaceutically acceptable excipients selected from….or any combination thereof”. However, this recitation is indefinite as it is not clear if the list of alternatives is closed or not. Proper Markush language requires that the group from which alternatives are being chosen be closed (for example: selected from the group consisting of a, b and c). The current claim does not recite “and” and instead recites “or any combination thereof”, which is indefinite because it is not clear what the group of alternatives encompasses and persons skilled in the art cannot determine the metes and bounds of the claimed invention. It is suggested that the “or” be replaced by “and” in the phrase “or any combination thereof”.
Claim Rejections - 35 USC § 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.
Claim(s) 1, 5-17, 20-22 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Sullivan et al. (US Pat. Pub. 2015/0141328 A1).
Sullivan et al. teach methods of stimulating human meibomian gland epithelial cell function by the administration of IGF-1 or an IGF-1 analogue (see [0011]). Sullivan et al. also teach that the IGF-1 can be administered as a pharmaceutical and that the pharmaceutical composition can include additional elements such as an ophthalmic demulcent, an excipient, an astringent, a vasoconstrictor and/or an emollient (see [0014]) and the IGF-1 which was administered in the experiments w dissolved in phosphate-buffered saline. Sullivan et al. teach that the method provides a therapeutically effective amount of IGF-1 or an IGF-1 analogue topically to the ocular surface or immediate vicinity of an eye of a patient showing signs or symptoms of meibomian gland dysfunction, evaporative dry eye, lipid abnormality of meibum or the tear film and/or Sjögren’s syndrome (see [0016]). Therefore, Sullivan et al. teach a method of treating dry eye disorder or Meibomian gland dysfunction in a subject in need thereof by locally administering to an eye or eyelid a pharmaceutical composition comprising a therapeutically effective amount of an IGF-1 variant having at least 90% sequence identity to IGF-1 (SEQ ID NO:1) wherein the local administration of the pharmaceutical composition results in an increase of lipid content of the Meibomian glands of the subject (see [0103] and [0121]). Sullivan et al. administer IGF-1 which is 100% identical to SEQ ID NO:1, thereby meeting the limitations of the claims.
Sullivan et al. does not specifically disclose that the pharmaceutical composition is administered via an eyedropper (see claim 5). However, Sullivan et al. clearly teach topical administration to the ocular surface of a subject or to an area immediately adjacent thereto (see claim 1 of Sullivan et al.). One of ordinary skill in the art would readily interpret this administration as encompassing using an eyedropper as this is the routine method of administering topical compositions to the ocular surface. Sullivan et al. also does not specifically disclose that the pharmaceutical composition is a “cream” (see claim 7). However, Sullivan et al. does teach acceptable excipients for the pharmaceutical compositions which include an emollient and emollients are commonly contained in eye gels and creams. Therefore, one of ordinary skill in the art would readily envision that a pharmaceutical composition which included an emollient as being a composition in the form of a gel or cream.
Claims 8-17 require particular physiological results to be obtained from the administration of the IGF-1 pharmaceutical composition to the subject. While Sullivan et al. did not measure/assess all of the outcomes recited in claims 8-17, Sullivan et al. does clearly disclose treating the same condition in the same patient population with the same pharmaceutical composition and therefore, the results of the administration would be inherent to the administration of the same composition to the same population for the same condition to be treated. Therefore, Sullivan et al. anticipate claims 8-17.
Claims 18-19 recite that the method does not comprise administration of any additional phopholipidosis-inducing agents or azithromycin or doxycycline. However, Sullivan et al. teaches that IGF-1 acts on human meibomian gland epithelial cells and stimulates proliferation, increases SREBP-1 expression and promotes lipid accumulation in these cells in the absence of any additional phopholipidosis-inducing agents or azithromycin or doxycycline. Sullivan et al. provides an analysis of why phopholipidosis-inducing agents and azithromycin or doxycycline are used in method of treating dry eye and meibomian gland dysfunction, but Sullivan et al. also provides for the use of IGF-1 alone (see [0002]).
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) 1 and 4 is/are rejected under 35 U.S.C. 103 as being unpatentable over Sullivan et al. (US Pat. Pub. 2015/0141328 A1) in view of WO 2015/169944 A1 (Speri et al.).
The disclosure of Sullivan et al. is provided above. Sullivan et al. does not specifically state that the local administration is performed daily.
WO 2015/169944 A1 teaches pharmaceutical compositions for the treatment of ocular diseases, including dry eye. ‘944 teaches that the frequency of administration of eye drop formulation is once daily or in the range from about one to about eight times a day (see claim 21).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the instant invention to practice the method of Sullivan et al. and to topically administer the pharmaceutical composition comprising IGF-1 on a daily basis. Eye treatments a typically administered as eye drops or as creams and require multiple applications, which are typically daily or multiple times daily as taught by ‘944. Therefore, practicing the method of Sullivan et al. with administration daily would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention.
Claim(s) 1-3 is/are rejected under 35 U.S.C. 103 as being unpatentable over Sullivan et al. (US Pat. Pub. 2015/0141328 A1) in view of Dubaquie‘ (Biochemistry 38: 6386-6396, 1999).
The disclosure of Sullivan et al. is provided above. Sullivan et al. does not teach an IGF-1 variant which a reduced affinity for at least one IGF binding protein or wherein the IGF-1 variant has an amino acid substitution at position 3 relative to wild-type IGF-1 of SEQ ID NO:1.
Dubaquie’ et al. teach that substitution of amino acid position 3 of IGF-1 results in an IGF-1 molecule with reduced binding affinity for IGF binding proteins. IGF-1 molecules which have substitutions at position 3 not only have reduced binding affinity for IGFBP1 and IGFBP3, but additionally IGF-1 molecules with reduced affinity for IGFBPs also have increased mitogenic potency due to the reduction in IGFBP binding (see page 6392, column 2, last paragraph)
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to practice the method of Sullivan et al. with the IGF-1 variant of Dubaquie’ et al. which has a substitution at position 3 of IGF-I and a reduced binding affinity for IGFBPs because Dubaquie’ et al.teach that IGF-1 mutants with decreased binding affinity for IGFBJP have increased mitogenic potency. One of ordinary skill in the art would be motivated to administer the IGF-1 molecule of Dubaquie’ et al. in the treatment method of Sullivan et al. because an IGF-1 with increased mitogenic potency would provide for administration of lower concentrations of IGF-1 to achieve the same result. One would have a reasonably expectation of success because the IGF-1 molecules of Dubaquie’ et al. still bind the IGF receptor and only the binding affinity for IGFBPs are impacted by the substitution at position 3. Therefore, the invention as a whole 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
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 filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual 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/apply/applying-online/eterminal-disclaimer.
Claims 1-22 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-15 of copending Application No. 19/300,509 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the claims encompass treating the same conditions with the same compound. The claims of ‘509 are limited to an IGF-1 variant comprising the amino acid sequence of SEQ ID NO:17. The IGF-1 molecule of the claims of ‘509 has the same amino acid sequence as that of IGF-1 with a substitution at positions 3 and 49. The substitution at position 3 reduces the affinity of IGF-1 for IGFBP, therefore, this molecule meets the limitations of instant claims 2-3. Additionally, this molecule has at least 97% sequence identity to SEQ ID NO:1, therefore, this molecule meets the limitations of the instant claims. ‘509 also claims pharmaceutical compositions which have the same composition as those administered in the instant claims as well as pharmaceutical forms to be administered and administration routes. Lastly, ‘509 details the therapeutic effects which would be achieved by administration of the pharmaceutical composition (claim 3) which are the same effects to be achieved by the claimed method (see claims 8-17). Lastly, ‘509 claims a method of treatment and methods of treating dry eye disease or Meibomian gland dysfunction would be obvious over the limitations in claims 12-13 which state that the purpose of the kit is for treating these conditions, which are the same conditions being treated in the instant application. Therefore, the instant claims are not patentably distinct from those of ‘509.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1-22 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 107-129 of copending Application No. 19/242,613 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the claims encompass treating the same conditions with the same compound. Claims 107-127 of ‘613 are directed to pharmaceutical compositions formulated for local administration to an eye comprising an IGF-1 variant. The IGF-1 molecule of the claims of ‘613 is the same as that recited in the instant claims (see claims 107-110 and 126-127 compared to claims 1-3 and 21-22 of the instant application). ‘613 also claims pharmaceutical compositions which have the same composition as those administered in the instant claims (see claims 111-112 and 118 compared to claims 5-7 and 20 of the instant application) as well as pharmaceutical forms to be administered and administration routes. Lastly, ‘613 details the therapeutic effects which would be achieved by administration of the pharmaceutical composition (see claims 113-116, 119-125) which are the same effects to be achieved by the claimed method (see claims 8-17). Lastly, ‘613 claims the same method as the instant application and use of any of the claimed pharmaceutical compositions of ‘613 in the method of claim 129 would be obvious. Therefore, the instant claims are not patentably distinct from those of ‘613.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
No claim is allowed.
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/Christine J Saoud/Primary Examiner, Art Unit 1645