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
Acknowledgments are made that this application claims the priority to the following:
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Information Disclosure Statement
The information disclosure statements (IDS) comply with the provisions of 37 CFR 1.97, 1.98 and MPEP § 609. Accordingly, they have been placed in the application file and the information therein has been considered as to the merits.
DETAILED ACTION
Applicant's response to election of species in the reply filed on 01/23/2026 is acknowledged.
However, in light of claim amendments, previous election of species is withdrawn and all species are examined in this office action.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 37-41 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 pre-AIA the applicant regards as the invention.
Claims recite aqueous pharmaceutical formulation and the specific amount of aflibercept in the claim language. However, independent claim of these dependent claims do not have these limitations. There is insufficient antecedent basis for these limitations in the claims.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102 of this title, 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.
The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 25-41 are rejected under 35 U.S.C. 103 as being unpatentable over Graham (US 2019/0343918 A1).
For claim 25:
Graham teaches a method of treating age related macular degeneration (wet), aka neovascular age-related macular degeneration, in a subject comprising administering aflibercept by intraocularly injection [see 0036, Example 10 and claims 30-38].
Graham further teaches the dosage amounts of aflibercept, ranges from 4 mg to 20 mg [see 0103, 0278 and 0284] or about 8 mg [see claims 30-33].
Graham further teaches that aflibercept is administered about every 2 weeks, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 7 weeks, 8 weeks, 9 weeks, 10 weeks, 11 weeks, 12 weeks, 13 weeks, 14 weeks, 15 weeks, 16 weeks, 17 weeks 18 weeks, 19 weeks, 20 weeks, 21, weeks, 22 weeks, 23 weeks or 24 weeks [see 0278 and see claims 30-38]. Each dose of high concentration VEGF receptor fusion protein, viz., aflibercept, to a subject over the course of a treatment may contain the same or substantially the same amount of fusion protein. Alternatively, the quantity of any one dose may be different or variable over a treatment course. [see 0283, 0298, Example 12].
The difference is that Graham is silent on or exemplified applicants recited specific order or specific interval timings.
However, Graham provided and described possible dosage amounts at different interval timings and so, based on guidance provided by Graham, a skilled person in the art would be motivated to explore other possible interval timings and arrive at applicants claimed invention with a reasonable expectation of success.
In addition, dosage amounts or concentrations of drugs and length of administrations etc., are result effective variables, because a skilled person in the art determine these variables through a routine experimentation and which is common practice in the art, absent evidence to the contrary. Generally, differences in concentrations of components of a formulation (or drug or tuning length of interval) will not support the patentability of subject matter encompassed by the prior art. Such formulations are results-effective variables which can be optimized. In in re Boesch, 617 F.2d 272,276, 205 USPQ 215, 219 (CCPA 1980), it was held that "discovery of an optimum value of a result effective variable in a known process is ordinarily within the skill of the art." Further, in In re Aller, 220 F. 2d454, 456, 105 USPQ 233,235 (CCPA 1955) the courts maintained that: "Where the general condition of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." As formulating optimal compositions for medicaments is routine in the art of pharmacology, the claims are considered to be prima facie obvious.
See Tyco Healthcare Group LP v. Mutual Pharmaceutical Co., 642 F.3d 1370 (Fed. Cir. 2011) (“the court observed that the parties did not dispute that ‘physicians always seek to prescribe the lowest effective dose of any medication’”). “[t]he test for obviousness is not whether the features of a secondary reference may be bodily incorporated into the structure of the primary reference; nor is it that the claimed invention must be expressly suggested in any one or all of the references. Rather, the test is what the combined teachings of the references would have suggested to those of ordinary skill in the art.” See In re Keller, 642 F.2d 413, 425 (CCPA 1981). Thus, it would be obvious to lower the concentration of a drug (or increase the length of interval) if a skilled person see adverse reactions/side effects even if a given patient population displays some heterogeneity in those results. Doctors are well skilled in the art and would expect this heterogeneity. See Peterson, 315 F.3d at 1330; see also KSR, 550 U.S. at 421 (“A person of ordinary skill is also a person of ordinary creativity, not an automaton.”).”
For claim 26-31:
As explained above, Graham teaches that aflibercept is administered about every 2 weeks, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 7 weeks, 8 weeks, 9 weeks, 10 weeks, 11 weeks, 12 weeks, 13 weeks, 14 weeks, 15 weeks, 16 weeks, 17 weeks 18 weeks, 19 weeks, 20 weeks, 21, weeks, 22 weeks, 23 weeks or 24 weeks [see 0278 and see claims 30-38]. Each dose of high concentration VEGF receptor fusion protein, viz., aflibercept, to a subject over the course of a treatment may contain the same or substantially the same amount of fusion protein. Alternatively, the quantity of any one dose may be different or variable over a treatment course. [see 0283, 0298, Example 12].
Applicants claimed range fall within the scope of above.
For claim 32:
Graham teaches the dosage amounts of aflibercept, ranges from 4 mg to 20 mg [see 0103, 0278 and 0284] or about 8 mg [see claims 30-33].
For claim 33:
See For claim 1 above.
For claim 34:
Graham teaches intravitreal injection to both eyes of the subject [see 0278, 0279, 0357 and claims 30-34].
For claim 35-36:
Graham teaches about 100 mL or 70 mL of aflibercept [see 0103, 0285 and claims 30-36].
For claims 37:
Graham teaches 114 mg/ml of aflibercept [see 0011, 0017 and 0065].
For claim 38-40:
Graham teaches 114.3 mg/ml VEGF receptor fusion protein (e.g., aflibercept) (e.g., 103-126 mg/ml), 10 mM histidine-based buffer (e.g., +1 mM), 5% (w/v) sucrose (e.g., +0.5%), 0.03% (w/v) polysorbate 20 (e.g., 0.02-0.04%), and 50 mM L-arginine monohydrochloride (e.g., +5 mM), with a pH of 5.8 (e.g., 5.6-6.0 or 5.5-6.1). [see 0242].
For claim 41:
Graham does not teach the recited conditions or limitations on subject(s), and so, the subjects in the disclosure of Graham are expected to be free from the recited conditions.
Based on the above established facts from the cited prior art, it appears that all the claimed elements, i.e, applicants aflibercept, its utility and its concentration ranges in the composition, were known in the prior art, and one skilled person in the art could have combined the elements as claimed by known relationships, with no change in their respective functions, and the combination would have yielded predictable results to one of ordinary skill in the art.
The motivation to modify the art can arise from the expectation that the prior art elements will perform their expected functions to achieve their expected results when combined for their common known purpose. See MPEP 2144.07. Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention by taking the advantage of the teaching of the above cited reference and to make the instantly claimed method with a reasonable expectation of success.
Claims 42-54 are rejected under 35 U.S.C. 103 as being unpatentable over Graham (US 2019/0343918 A1).
For claim 42:
Graham teaches a method of treating age related macular degeneration (wet), aka neovascular age-related macular degeneration, in a subject comprising administering aflibercept by intraocularly injection [see 0036, Example 10 and claims 30-38].
Graham further teaches the dosage amounts of aflibercept, ranges from 4 mg to 20 mg [see 0103, 0278 and 0284] or about 8 mg [see claims 30-33].
Graham teaches 114 mg/ml of aflibercept [see 0011, 0017 and 0065].
Graham further teaches that aflibercept is administered about every 2 weeks, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 7 weeks, 8 weeks, 9 weeks, 10 weeks, 11 weeks, 12 weeks, 13 weeks, 14 weeks, 15 weeks, 16 weeks, 17 weeks 18 weeks, 19 weeks, 20 weeks, 21, weeks, 22 weeks, 23 weeks or 24 weeks [see 0278 and see claims 30-38]. Each dose of high concentration VEGF receptor fusion protein, viz., aflibercept, to a subject over the course of a treatment may contain the same or substantially the same amount of fusion protein. Alternatively, the quantity of any one dose may be different or variable over a treatment course. [see 0283, 0298, Example 12].
The difference is that Graham is silent on or exemplified applicants recited specific order or specific interval timings.
However, Graham provided and described possible dosage amounts at different interval timings and so, based on guidance provided by Graham, a skilled person in the art would be motivated to explore other possible interval timings and arrive at applicants claimed invention with a reasonable expectation of success.
In addition, dosage amounts or concentrations of drugs and length of administrations etc., are result effective variables, because a skilled person in the art determine these variables through a routine experimentation and which is common practice in the art, absent evidence to the contrary. Generally, differences in concentrations of components of a formulation (or drug or tuning length of interval) will not support the patentability of subject matter encompassed by the prior art. Such formulations are results-effective variables which can be optimized. In in re Boesch, 617 F.2d 272,276, 205 USPQ 215, 219 (CCPA 1980), it was held that "discovery of an optimum value of a result effective variable in a known process is ordinarily within the skill of the art." Further, in In re Aller, 220 F. 2d454, 456, 105 USPQ 233,235 (CCPA 1955) the courts maintained that: "Where the general condition of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." As formulating optimal compositions for medicaments is routine in the art of pharmacology, the claims are considered to be prima facie obvious.
See Tyco Healthcare Group LP v. Mutual Pharmaceutical Co., 642 F.3d 1370 (Fed. Cir. 2011) (“the court observed that the parties did not dispute that ‘physicians always seek to prescribe the lowest effective dose of any medication’”). “[t]he test for obviousness is not whether the features of a secondary reference may be bodily incorporated into the structure of the primary reference; nor is it that the claimed invention must be expressly suggested in any one or all of the references. Rather, the test is what the combined teachings of the references would have suggested to those of ordinary skill in the art.” See In re Keller, 642 F.2d 413, 425 (CCPA 1981). Thus, it would be obvious to lower the concentration of a drug (or increase the length of interval) if a skilled person see adverse reactions/side effects even if a given patient population displays some heterogeneity in those results. Doctors are well skilled in the art and would expect this heterogeneity. See Peterson, 315 F.3d at 1330; see also KSR, 550 U.S. at 421 (“A person of ordinary skill is also a person of ordinary creativity, not an automaton.”).”
For claim 43-46:
Graham teaches both histidine and phosphate based buffers for their aqueous pharmaceutical formulation and the buffers further comprising trehalose and sucrose [see 0013-0014].
For claim 47-54:
Graham teaches about 100 mL or 70 mL of aflibercept [see 0103, 0285 and claims 30-36]. For remaining limitations, see the provided reasoning in For claim 42 above.
Based on the above established facts from the cited prior art, it appears that all the claimed elements, i.e, applicants aflibercept, its utility and its concentration ranges in the composition, were known in the prior art, and one skilled person in the art could have combined the elements as claimed by known relationships, with no change in their respective functions, and the combination would have yielded predictable results to one of ordinary skill in the art.
The motivation to modify the art can arise from the expectation that the prior art elements will perform their expected functions to achieve their expected results when combined for their known purpose. See MPEP 2144.07. Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention by taking the advantage of the teaching of the above cited reference and to make the instantly claimed method with a reasonable expectation of success.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SUDHAKAR KATAKAM whose telephone number is (571)272-9929. The examiner can normally be reached 8:30 am to 5 pm.
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SUDHAKAR KATAKAM
Primary Examiner
Art Unit 1658
/SUDHAKAR KATAKAM/Primary Examiner, Art Unit 1658